A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)

Phase 3

Recruiting

Conditions: Stage I Kidney Wilms Tumor
Stage II Kidney Wilms Tumor
Stage III Kidney Wilms Tumor
Stage IV Kidney Wilms Tumor

Interventions: Procedure: Computed Tomography
Procedure: Nephrectomy
Procedure: Bone Scan
Drug: Carboplatin
Drug: Cyclophosphamide
Biological: Dactinomycin
Other: Patient Observation
Drug: Doxorubicin
Drug: Etoposide
Procedure: Magnetic Resonance Imaging
Procedure: Positron Emission Tomography
Drug: Irinotecan
Procedure: Ultrasound Imaging
Drug: Vincristine
Procedure: X-Ray Imaging

Registration Number: NCT06401330

Lead Sponsor: Children's Oncology Group

Brief Summary: This phase III trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.

Detailed Description: PRIMARY OBJECTIVES:

I. To maintain event-free survival (EFS) for Stage I favorable histology Wilms tumor (FHWT) patients without adverse biology who are also (1) 2 to \< 4 years of age, OR (2) age \< 2 years with tumor weight of 550 grams or more, OR (3) age 4+ years with epithelial histology subtype while reducing post-nephrectomy therapy from vincristine, actinomycin (EE-4A) to Nephrectomy Only. (Stage I Nephrectomy Only Stratum 2) II. To improve EFS for Stage I FHWT patients with age \< 2 years AND nephrectomy weight \< 550g AND whose tumors have adverse biology by treating with EE-4A instead of Nephrectomy Only. (Stage I EE-4A Stratum 3) III. To evaluate whether addition of vincristine and irinotecan to standard EE-4A (novel vincristine, actinomycin, irinotecan \[Regimen VIVA\]) is non-inferior to vincristine, actinomycin, doxorubicin (DD-4A) in terms of EFS among Stage II FHWT patients whose tumors demonstrate adverse biology. (Stage II: VIVA versus \[vs\] DD-4A Randomization) IV. To evaluate whether omission of doxorubicin (EE-4A) is non-inferior to historical DD-4A in Stage III FHWT patients with standard biology or post-therapy blastemal predominance. (Stage III: EE-4A) V. To demonstrate the non-inferiority of vincristine, actinomycin, doxorubicin, cyclophosphamide, etoposide and irinotecan (Regimen MVI) to vincristine, dactinomycin, doxorubicin, cyclophosphamide and etoposide (Regimen M) in the treatment of Stage III FHWT patients whose tumors exhibit adverse biology (post-chemotherapy blastemal predominance excluded). (Stage III: Regimen MVI vs Regimen M Randomization) VI. To demonstrate the non-inferiority of Regimen MVI to Regimen M in the treatment of Stage IV FHWT patients with adverse biology, slow incomplete lung response (SIR), or extrapulmonary metastases (EPM) (post-therapy blastemal predominance excluded). (Stage IV: Regimen MVI vs Regimen M Randomization) VII. To demonstrate the superiority of vincristine, doxorubicin, cyclophosphamide, etoposide, carboplatin and irinotecan (Regimen UH-3) vs historical DD-4A or Regimen M in treatment of Stage III or IV FHWT patients with blastemal predominance at delayed nephrectomy. (Stage III-IV: UH-3 (Blastemal Predominance)

SECONDARY OBJECTIVES:

I. To describe outcomes for Stage I FHWT patients without adverse biology who are either less than 4 years of age OR 4+ years of age with epithelial subtype who are treated with Nephrectomy Only and assess consistency with a matched historical control from the prior Children's Oncology Group (COG) therapeutic era. (Stage I: Nephrectomy Only) II. To describe outcomes for Stage I FHWT patients with adverse biology OR age \> 4 and not epithelial subtype who are treated with post-nephrectomy EE-4A and assess consistency with a matched historical control from the prior COG therapeutic era. (Stage I: EE-4A) III. To describe overall survival in the cohort of modified very low risk (mVLR) patients who relapse following treatment with nephrectomy only and are assigned at relapse to DD-4A (if presumed or confirmed favorable histology Wilms tumor at relapse) or UH-3 (if evidence of anaplasia at relapse). (Stage I: Nephrectomy Only Relapse) IV. To describe outcomes for Stage II FHWT patients without adverse biology who are treated with post-nephrectomy EE-4A and assess consistency with a matched historical control from the prior COG therapeutic era. (Stage II: EE-4A) V. To compare outcomes of Stage II FHWT patients whose tumors are negative for combined loss of heterozygosity (LOH) but positive for 1q gain who are randomized to VIVA vs DD-4A on AREN2231 against historically matched patients treated with EE-4A during the prior COG therapeutic era. (Stage II VIVA vs DD-4A Stratum 1) VI. To compare outcomes of Stage II FHWT patients whose tumors are positive for combined LOH 1p AND 16q and who are randomized to VIVA vs DD-4A on AREN2231 against historically matched patients treated with DD-4A during the prior COG therapeutic era. (Stage II VIVA vs DD-4A Stratum 2) VII. To compare outcomes of Stage III FHWT patients whose tumors have adverse biology other than combined LOH and who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with DD-4A during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage III Regimen MVI vs Regimen M Stratum 1) VIII. To compare outcomes of Stage III FHWT patients whose tumors have combined LOH and who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with Regimen M during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage III Regimen MVI vs Regimen M Stratum 2) IX. To describe outcomes for Stage IV FHWT patients with rapid complete response of lung only metastases and no adverse biology who are treated with DD-4A on AREN2231 and assess consistency with a matched historical control from the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV: DD-4A) X. To compare outcomes of Stage IV lung only patients with either combined LOH 1p AND 16q or SIR who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with Regimen M during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV Regimen MVI vs Regimen M Stratum 1) XI. To compare outcomes of Stage IV lung only rapid complete response (RCR) patients without combined LOH 1p AND 16q who are positive for other adverse biological factors and who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with DD-4A during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV Regimen MVI vs Regimen M Stratum 2) XII. To compare outcomes of Stage IV patients with extrapulmonary metastases (EPM) who are randomized to Regimen MVI vs Regimen M on AREN2231 against historically matched patients treated with Regimen M during the prior COG therapeutic era (post-chemotherapy blastemal predominance excluded). (Stage IV Regimen MVI vs Regimen M Stratum 3) XIII. To report a pooled comparison of Regimen MVI vs Regimen M in Stage III or Stage IV randomized patients. (Stage III-IV Regimen MVI vs Regimen M) XIV. To compare outcomes of Stage III or IV FHWT patients with blastemal predominance at delayed nephrectomy who are treated with Regimen UH-3 on AREN2231 vs a historically matched cohort that received DD-4A in the prior COG therapeutic era. (Stage III-IV UH-3 Stratum 1) XV. To compare outcomes of Stage III or IV FHWT patients with blastemal predominance at delayed nephrectomy who are treated with Regimen UH-3 on AREN2231 vs a historically matched cohort that received Regimen M in the prior COG therapeutic era. (Stage III-IV UH-3 Stratum 2) XVI. To describe outcomes of Stage III or IV FHWT patients with delayed nephrectomy occurring after the start of Cycles 3 or 4 (super delayed) who are assigned to Regimen M or continued DD4A. (Stage III-IV Super Delayed Nephrectomy)

EXPLORATORY OBJECTIVES:

I. To determine the impact of imaging schedule and modality (chest x-ray \[CXR\], ultrasound \[US\], versus computed tomography/magnetic resonance imaging \[CT/MRI\], versus clinical symptoms) on relapse, timing of detection of relapse, burden of disease at relapse (as assessed by retrospective central imaging review), as well as impact on survival.

II. To analyze the impact of radiologically determined pulmonary tumor burden on outcomes.

III. To assess whether imaging modality (ultrasound, CT, MRI with or without hepatocyte specific contrast agent) at diagnosis is associated with detection of increased number of liver metastases, and whether modality choice impacts surgery and/or radiation planning for liver metastases.

IV. To accurately describe the responses of extrapulmonary metastases to the various therapeutic modalities (chemotherapy, radiation therapy, and surgery) through central review of institutional imaging at various stages of treatment, and to correlate institutionally interpreted radiologic response interpretations with central review.

V. To describe the association of the number of anatomically relevant and pathologically confirmed lymph nodes sampled and percent of positive lymph nodes (LNs) on EFS and overall survival \[OS\].

VI. To document the surgical and/or medical rationale and approach for biopsy (including type of biopsy, number of biopsies, and site of biopsy) for all patients who are treated with the approach of initial biopsy and delayed nephrectomy.

VII. To describe sites of recurrence for patients with liver metastases according to the surgery and/or radiation therapy administered for residual liver lesions at Week 6 and 12.

VIII. To increase the number of patients eligible to avoid lung radiation therapy (RT) by encouraging resection of residual pulmonary nodules for patients defined as Stage IV FHWT with standard biology and who have 1-3 residual pulmonary nodules on imaging after Cycle 2, by omitting lung RT for those who are found to have no viable tumor in resected nodules.

IX. To describe whether residual lung lesions at end of therapy are associated with relapse.

X. To improve the reliability of data derived from central surgical review through the implementation of a standardized operative note.

XI. To describe the treatment, perioperative morbidity and outcome of patients noted to have inferior vena cava (IVC) tumor thrombus at time of diagnosis, including surgical approach, pathology findings and specific radiation therapy received.

XII. To determine the feasibility of employing intensity modulated radiation therapy (IMRT) with central quality assurance (QA) monitoring within the prescribed time frame.

XIII. To determine the lung tumor and liver tumor control rate using intensity modulated radiation therapy (IMRT) and/or proton therapy and compare it to standard 3-dimensional radiotherapy in the current study and the AREN0533 study.

XIV. To determine the flank and abdominal tumor control rates in children with Stage IV FHWT who received abdominal radiotherapy after 2 cycles of chemotherapy in this study (delayed abdominal radiation) and compare it to AREN0533 study where abdominal radiotherapy was performed within 2 weeks of nephrectomy (upfront abdominal radiation).

XV. To compare abdominal relapse according to protocol-recommended radiotherapy fields (flank vs. whole abdominal) in the current study and compare it to the abdominal relapse according to radiotherapy fields (flank vs. whole abdominal) in the AREN0532 and AREN0533 studies.

XVI. To determine the impact of radiotherapy on local and distant control rates for EPM sites and compare them to EPM sites not receiving radiation.

XVII. To describe the rate and severity of recurrent hepatotoxicity in patients who undergo re-introduction of chemotherapy after experiencing hepatopathy.

XVIII. To collect serial blood and urine samples to bank for future research studies.

OUTLINE:

STAGE I FHWT: Patients \< 4 years old at diagnosis or with epithelial FHWT, regardless of age, undergo observation until disease relapse. At the time of disease relapse, patients with adverse biology are assigned to Arm I, and patients with standard biology are assigned to Arm II. Patients ≥ 4 years of age at diagnosis without epithelial FHWT are assigned to Arm I without

* ARM I: Patients receive the EE-4A regimen: Dactinomycin intravenously (IV) over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

* ARM II: Patients undergo nephrectomy on study.

STAGE II FHWT: Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients with standard biology are assigned to Arm I below. Patients with adverse biology are randomized to Arm II or Arm III below.

* ARM I: Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I.

* ARM II: Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-8, irinotecan IV over 90 minutes daily on days 1-5 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

* ARM III: Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

STAGE III FHWT: Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients with standard biology are assigned to Arm I below. Patients with adverse biology are assigned to Arm II below.

* ARM I: Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I.

* ARM II: Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above.

* ARM IIA: Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity.

* ARM IIB: Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY): Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above.

* PATIENTS ABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology and low or intermediate risk histology are assigned to Arm I below. Patients with high risk histology are assigned to Arm II below. Patients with adverse biology are randomized to Arm III or Arm IV below.

* PATIENTS UNABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology are assigned to Arm V below. Patients with adverse biology are randomized to Arm VI or Arm VII below.

* ARM I: Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above.

* ARM II: Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity.

* ARM III: Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above.

* ARM IV: Patients receive the M regimen as in STAGE III FHWT Arm IIB above.

* ARM V: Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients with low or intermediate risk histology without LOH 1p or 16q genetic results are then assigned to Arm VA. Patients with low or intermediate risk histology, positive lymph nodes, and 1p or 16q genetic results are then assigned to Arm VB. Patients with high risk histology are assigned to Arm VIII below.

* ARM VA: Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above.

* ARM VB: Patients receive the M regimen as in STAGE III FHWT Arm IIB above.

* ARM VI: Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients with high risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm IX.

* ARM VII: Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients with high risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm X.

* ARM VIII: Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above.

* ARM IX: Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above.

* ARM X: Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above.

STAGE IV FHWT LUNG METASTASES (UPFRONT NEPHRECTOMY): Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients with standard biology and rapid complete lung response (RCR) are assigned to Arm I below. Patients with standard biology and slow incomplete lung response (SIR), or adverse biology are randomized to Arm II or Arm III below.

* ARM I: Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above.

* ARM II: Patients receive the M regimen as in STAGE III FHWT Arm IIB above.

* ARM III: Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above.

STAGE IV FHWT LUNG METASTASES (UPFRONT BIOPSY/DELAYED NEPHRECTOMY): Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above.

* PATIENTS ABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology, low or intermediate risk histology, and RCR are assigned to Arm I below. Patients with high risk histology are assigned to Arm II below. Patients with adverse biology and low or intermediate risk histology are randomized to Arm III or Arm IV below.

* PATIENTS UNABLE TO UNDERGO A DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with standard biology and RCR are assigned to Arm V below. Patients with standard biology and SIR OR adverse biology and either SIR or RCR are randomized to Arm VI or Arm VI below.

* ARM I: Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above.

* ARM II: Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II.

* ARM III: Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above.

* ARM IV: Patients receive the M regimen as in STAGE III FHWT Arm IIB above.

* ARM V: Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients with low or intermediate risk histology without LOH 1p or 16q genetic results are then assigned to Arm VA. Patients with low or intermediate risk histology, positive lymph nodes, and 1p or 16q genetic results are then assigned to Arm VB. Patients with high risk histology are assigned to Arm VIII below.

* ARM VA: Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above.

* ARM VB: Patients receive the M regimen as in STAGE III FHWT Arm IIB above.

* ARM VI: Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients with high risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm IX.

* ARM VII: Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients with high risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm VIII. Patients with low or intermediate risk histology after delayed nephrectomy in cycle 3 or 4 are assigned to Arm X.

* ARM VIII: Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above.

* ARM IX: Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above.

* ARM X: Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above.

STAGE IV FHWT EXTRAPULMONARY METASTASES: Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above.

PATIENTS ABLE TO UNDERGO UPFRONT NEPHRECTOMY: Patients are randomized to Arm I or II below.

PATIENTS ABLE TO UNDERGO DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with low or intermediate risk histology are randomized to Arm III or IV.

PATIENTS ABLE TO UNDERGO DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients with high risk histology are assigned to Arm V.

PATIENTS UNABLE TO UNDERGO DELAYED NEPHRECTOMY AFTER CYCLE 2: Patients are randomized to Arm VI or VII.

* ARM I: Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above.

* ARM II: Patients receive the M regimen as in STAGE III FHWT Arm IIB above.

* ARM III: Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above.

* ARM IV: Patients receive the M regimen as in STAGE III FHWT Arm IIB above.

* ARM V: Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above.

* ARM VI: Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients undergoing nephrectomy after cycles 3 or 4 and with low or intermediate risk histology are assigned to Arm IX below. Patients undergoing nephrectomy after cycles 3 or 4 and with high risk histology are assigned to Arm VIII below

* ARM VII: Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients undergoing nephrectomy after cycles 3 or 4 and with low or intermediate risk histology are assigned to Arm X below. Patients undergoing nephrectomy after cycles 3 or 4 and with high risk histology are assigned to Arm VIII below.

* ARM VIII: Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above.

* ARM IX: Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above.

* ARM X: Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above.

* NOTE: Patients receiving EE-4A, DD-4A \& VIVA regimens also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial. Patients receiving M, MVI \& UH3 regimens also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/positron emission tomography (PET) scans throughout the trial.

After completion of study treatment, patients are followed for 10 years.

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 1656

Inclusion Criteria

Patients must be enrolled on APEC14B1 and consent to Part A - Eligibility Screening prior to enrollment on AREN2231.
Patients must be < 30 years old at enrollment.
Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor confirmed by central review and with a qualifying Initial Stratum Assignment on APEC14B1.
Patients must receive a qualifying Initial Stratum Assignment on APEC14B1 by Day 14 post-diagnostic procedure (nephrectomy or biopsy), where that procedure is Day 0.
- Patients must enroll on AREN2231 by Day 14.
- Exceptions: If patient reaches Day 14 (post initial diagnostic nephrectomy or biopsy) without receiving an Initial Stratum Assignment on APEC14B1, patient will not be eligible for enrollment on AREN2231 unless all required materials (reports and Case Report Forms and specimens) for an Initial Stratum Assignment arrived by Day 7, but an Initial Stratum Assignment was not completed by Day 14. In these circumstances, after obtaining appropriate protocol consent, the patient may proceed with treatment according to local institutional staging and enroll within 5 calendar days of notification of the central Initial Stratum Assignment being issued, only if the AREN2231 Initial Stratum Assignment is in agreement with any treatment already initiated. If the Initial Stratum Assignment is not in agreement with the local institution's assessment then the patient will be ineligible for AREN2231.
All sites must have sent or plan to send diagnostic tumor sample for molecular testing through a Clinical Laboratory Improvement Act (CLIA)-certified (or equivalent if outside of the United States [US]) laboratory that can detect Loss of Heterozygosity (LOH) of chromosome 1p AND 16q, and gain of chromosome 1q. Patients potentially eligible for mVLR must also have LOH of chromosome 11p15 included.
- Note: Patients are eligible for enrollment before these results are available; however, molecular results must be returned and uploaded to APEC14B1 for integration into risk stratification by the required timepoints (specific timelines vary by treatment arm). Patients who do not have molecular results available by the arm-specific timepoints may be taken off protocol therapy.
Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible.
- Note: Lymph node sampling will also be required at delayed nephrectomy. Patients who do not have a lymph node sampled and confirmed as a lymph node by central pathology review at delayed nephrectomy will be taken off protocol therapy.
Karnofsky performance status must be 50 for patients > 16 years of age and the Lansky performance status must be 50 for patients ≤ 16 years of age.
Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR direct bilirubin ≤ 3X ULN for subjects with total bilirubin levels > 1.5 ULN (within 7 days prior to enrollment).
Aspartate aminotransferase (AST/serum glutamate oxaloacetic transaminase [SGOT]) OR alanine transaminase (ALT/serum glutamic pyruvate transaminase [SGPT]) ≤ 3X ULN OR ≤ 5 X ULN for patients with liver metastases (within 7 days prior to enrollment).
Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% (within 7 days prior to enrollment)
- Note: This criteria only applies to patients centrally classified as Stage IV. Stage II and III patients subsequently assigned to a doxorubicin arm will be off protocol therapy if they do not meet this criteria at time of cardiac function assessment.
Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
All patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion Criteria

Patient with a diagnosis of Stage V Bilateral Wilms Tumor.
Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible.
Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure.
Patients with Stage I FHWT with a known or suspected Wilms Tumor predisposition syndrome or condition (contralateral nephrogenic rests and/or unilateral multicentric tumors) are excluded from treatment on the mVLR (Nephrectomy Only) arm.
- Notes:
  - In the context of the renal tumor protocols, multicentric tumors and multifocal tumors are equivalent terms, and refer to the occurrence of two or more tumors arising within one kidney.
  - Exclusion from the Nephrectomy Only arm applies to two groups of patients:
    - Patients < 4 years with Stage I FHWT other than epithelial subtype AND
    - Stage I patients of any age with Epithelial WT
  - For the purpose of exclusion from the Nephrectomy Only Arm, known or suspected WT predisposition syndromes or conditions are defined as follows:
    - WT Predisposition Syndromes: Beckwith Wiedemann Spectrum, Denys Drash, Trisomy 18, Idiopathic Hemihypertrophy/Isolated Lateralized Overgrowth, WAGR, Simpson-Golabi-Behmel, Bohring-Opitz, or other conditions considered by treating physician to predispose to WT.
    - WT Predisposing Conditions:
      - A unilateral WT and (radiologic or pathologic) determination of contralateral nephrogenic rest(s) AND/OR
      - Unilateral multicentric WT
Patients treated with partial nephrectomy at initial diagnosis are excluded from mVLR (Nephrectomy Only) arm.
Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor.
- Please note: Those with lung metastases as the only metastatic site who have complete resection of all radiologically evident lung nodules after enrollment but prior to the lung imaging following Cycle 2 of DD-4A will be inevaluable for lung assessment and subsequent stratum assignment and will, therefore, come Off Protocol Therapy.
Patients who have had prior tumor-directed chemotherapy or radiotherapy for the current diagnosis except for therapy delivered for an emergent issue, as medically indicated.
Patients who will potentially require doxorubicin on this study and have previously received doxorubicin for another diagnosis.
Patients receiving concurrent chemotherapy for a different diagnosis.
Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
Lactating females who plan to breastfeed their infants.
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stage III, Arm X-Upfront/Delayed (M)	Cyclophosphamide	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Dactinomycin	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Doxorubicin	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Etoposide	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Magnetic Resonance Imaging	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Positron Emission Tomography	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage I, Arm I (EE-4A)	Computed Tomography	Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Ultrasound Imaging	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Vincristine	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	X-Ray Imaging	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)	Computed Tomography	Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)	Dactinomycin	Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)	Doxorubicin	Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm I (EE-4A)	Dactinomycin	Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm I (EE-4A)	Magnetic Resonance Imaging	Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm I (EE-4A)	Patient Observation	Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm I (EE-4A)	Ultrasound Imaging	Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm I (EE-4A)	Vincristine	Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm I (EE-4A)	X-Ray Imaging	Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage I, Arm II (nephrectomy)	Nephrectomy	Patients undergo nephrectomy on study.
Stage I, Arm II (nephrectomy)	Patient Observation	Patients undergo nephrectomy on study.
Stage II, Arm I (EE-4A)	Computed Tomography	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm I (EE-4A)	Dactinomycin	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm I (EE-4A)	Magnetic Resonance Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm I (EE-4A)	Ultrasound Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm I (EE-4A)	Vincristine	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm I (EE-4A)	X-Ray Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)	Magnetic Resonance Imaging	Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)	Ultrasound Imaging	Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)	Vincristine	Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A)	X-Ray Imaging	Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Bone Scan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage II, Arm II (EE-4A, DD-4A)	Computed Tomography	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Carboplatin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage II, Arm II (EE-4A, DD-4A)	Dactinomycin	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm II (EE-4A, DD-4A)	Doxorubicin	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm II (EE-4A, DD-4A)	Magnetic Resonance Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm II (EE-4A, DD-4A)	Ultrasound Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm II (EE-4A, DD-4A)	Vincristine	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm II (EE-4A, DD-4A)	X-Ray Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, VIVA)	Computed Tomography	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, VIVA)	Dactinomycin	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, VIVA)	Doxorubicin	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, VIVA)	Magnetic Resonance Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, VIVA)	Ultrasound Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, VIVA)	Vincristine	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage II, Arm III (EE-4A, VIVA)	X-Ray Imaging	Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I (DD-4A, EE-4A)	Computed Tomography	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I (DD-4A, EE-4A)	Dactinomycin	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I (DD-4A, EE-4A)	Magnetic Resonance Imaging	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I (DD-4A, EE-4A)	Ultrasound Imaging	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I (DD-4A, EE-4A)	Vincristine	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I (DD-4A, EE-4A)	X-Ray Imaging	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)	Computed Tomography	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)	Dactinomycin	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)	Doxorubicin	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)	Magnetic Resonance Imaging	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)	Ultrasound Imaging	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)	Vincristine	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II (DD-4A)	X-Ray Imaging	Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Carboplatin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Cyclophosphamide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Cyclophosphamide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Etoposide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Irinotecan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Positron Emission Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Bone Scan	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Computed Tomography	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Etoposide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Irinotecan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm IIA (MVI)	Bone Scan	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Computed Tomography	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Cyclophosphamide	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Dactinomycin	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Doxorubicin	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Etoposide	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Irinotecan	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Cyclophosphamide	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Magnetic Resonance Imaging	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Positron Emission Tomography	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Ultrasound Imaging	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	Vincristine	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm III-Upfront-Delayed (DD-4A, MVI)	X-Ray Imaging	Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Bone Scan	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Computed Tomography	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Dactinomycin	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Doxorubicin	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Etoposide	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Magnetic Resonance Imaging	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Positron Emission Tomography	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Dactinomycin	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Ultrasound Imaging	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	Vincristine	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IV-Upfront-Delayed (DD-4A, M)	X-Ray Imaging	Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Bone Scan	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Computed Tomography	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Doxorubicin	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Etoposide	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Irinotecan	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Magnetic Resonance Imaging	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Positron Emission Tomography	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Ultrasound Imaging	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	Vincristine	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIA (MVI)	X-Ray Imaging	Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Bone Scan	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Computed Tomography	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Cyclophosphamide	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Dactinomycin	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Doxorubicin	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Etoposide	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Irinotecan	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Magnetic Resonance Imaging	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Positron Emission Tomography	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Ultrasound Imaging	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	Vincristine	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm IX-Upfront-Delayed (MVI)	X-Ray Imaging	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)	Computed Tomography	Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)	Dactinomycin	Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)	Doxorubicin	Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)	Magnetic Resonance Imaging	Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)	Ultrasound Imaging	Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)	Vincristine	Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm V-Upfront-Delayed (DD-4A)	X-Ray Imaging	Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)	Computed Tomography	Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)	Dactinomycin	Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)	Doxorubicin	Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)	Magnetic Resonance Imaging	Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)	Ultrasound Imaging	Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)	Vincristine	Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VA-Upfront-Delayed (DD-4A)	X-Ray Imaging	Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Bone Scan	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Computed Tomography	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Cyclophosphamide	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Dactinomycin	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Doxorubicin	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Etoposide	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Magnetic Resonance Imaging	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Positron Emission Tomography	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Ultrasound Imaging	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	Vincristine	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VB-Upfront-Delayed (M)	X-Ray Imaging	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Bone Scan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Cyclophosphamide	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Dactinomycin	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Doxorubicin	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Etoposide	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Magnetic Resonance Imaging	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Positron Emission Tomography	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Ultrasound Imaging	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	Vincristine	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IIB (M)	X-Ray Imaging	Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Bone Scan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Cyclophosphamide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Etoposide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Irinotecan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Positron Emission Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm III-Upfront/Delayed (DD-4A, MVI)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Bone Scan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Cyclophosphamide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Etoposide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Positron Emission Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IV-Upfront/Delayed (DD-4A, M)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Bone Scan	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Computed Tomography	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Cyclophosphamide	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Dactinomycin	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Etoposide	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Irinotecan	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Magnetic Resonance Imaging	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Positron Emission Tomography	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Ultrasound Imaging	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	Vincristine	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm IX-Upfront/Delayed (MVI)	X-Ray Imaging	Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm V-Upfront/Delayed (DD-4A)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)	Computed Tomography	Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)	Dactinomycin	Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)	Doxorubicin	Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)	Magnetic Resonance Imaging	Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)	Ultrasound Imaging	Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)	Vincristine	Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VA-Upfront/Delayed (DD-4A)	X-Ray Imaging	Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Computed Tomography	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Cyclophosphamide	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Dactinomycin	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Doxorubicin	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Etoposide	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Magnetic Resonance Imaging	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Positron Emission Tomography	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	Ultrasound Imaging	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VB-Upfront/Delayed (M)	X-Ray Imaging	Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Bone Scan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Positron Emission Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Bone Scan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Cyclophosphamide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Etoposide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Positron Emission Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VII-Upfront/Delayed (DD-4A, M)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Bone Scan	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Carboplatin	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Computed Tomography	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Cyclophosphamide	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Doxorubicin	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Etoposide	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Irinotecan	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Magnetic Resonance Imaging	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Positron Emission Tomography	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Ultrasound Imaging	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	Vincristine	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm VIII-Upfront/Delayed (UH-3)	X-Ray Imaging	Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Bone Scan	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage III, Arm X-Upfront/Delayed (M)	Computed Tomography	Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Cyclophosphamide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Etoposide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Irinotecan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Positron Emission Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Bone Scan	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Computed Tomography	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Cyclophosphamide	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Dactinomycin	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Doxorubicin	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Etoposide	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Magnetic Resonance Imaging	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Positron Emission Tomography	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Ultrasound Imaging	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	Vincristine	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VII-Upfront-Delayed (DD-4A, M)	X-Ray Imaging	Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Bone Scan	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Carboplatin	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Computed Tomography	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Cyclophosphamide	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Doxorubicin	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Etoposide	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Irinotecan	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Magnetic Resonance Imaging	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Positron Emission Tomography	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Ultrasound Imaging	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	Vincristine	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm VIII-Upfront-Delayed (UH-3)	X-Ray Imaging	Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Bone Scan	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Computed Tomography	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Cyclophosphamide	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Dactinomycin	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Doxorubicin	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Etoposide	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Magnetic Resonance Imaging	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Positron Emission Tomography	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Ultrasound Imaging	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	Vincristine	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Arm X-Upfront-Delayed (M)	X-Ray Imaging	Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Bone Scan	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Dactinomycin	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Etoposide	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Irinotecan	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	Vincristine	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm I (DD-4A, MVI)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Bone Scan	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Dactinomycin	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Etoposide	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	Vincristine	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm II (DD-4A, M)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Bone Scan	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Etoposide	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Irinotecan	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	Vincristine	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm III (DD-4A, MVI)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Bone Scan	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Dactinomycin	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Etoposide	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	Vincristine	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IV (DD-4A, M)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Bone Scan	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Dactinomycin	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Etoposide	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Irinotecan	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	Vincristine	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm IX (MVI)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Bone Scan	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Carboplatin	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Dactinomycin	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Etoposide	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Irinotecan	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	Vincristine	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm V (DD-4A, UH-3)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Bone Scan	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Dactinomycin	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Etoposide	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Irinotecan	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	Vincristine	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VI (DD-4A, MVI)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Bone Scan	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Dactinomycin	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Etoposide	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	Vincristine	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VII (DD-4A, M)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Bone Scan	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Carboplatin	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Etoposide	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Irinotecan	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	Vincristine	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm VIII (UH-3)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Bone Scan	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Computed Tomography	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Cyclophosphamide	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Doxorubicin	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Etoposide	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Magnetic Resonance Imaging	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Positron Emission Tomography	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Ultrasound Imaging	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	Vincristine	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Extrapulmonary Arm X (M)	X-Ray Imaging	Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm I (DD-4A)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm I (DD-4A)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm I (DD-4A)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm I (DD-4A)	Magnetic Resonance Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm I (DD-4A)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm I (DD-4A)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm I (DD-4A)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Bone Scan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Computed Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Cyclophosphamide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Dactinomycin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Doxorubicin	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Etoposide	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Irinotecan	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Positron Emission Tomography	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Ultrasound Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	Vincristine	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm II (DD-4A, M)	X-Ray Imaging	Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Bone Scan	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Computed Tomography	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Cyclophosphamide	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Dactinomycin	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Doxorubicin	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Etoposide	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Magnetic Resonance Imaging	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Positron Emission Tomography	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Ultrasound Imaging	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	Vincristine	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.
Stage IV Lung Metastases Arm III (DD-4A, MVI)	X-Ray Imaging	Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Primary Outcome Measures

Name	Time	Method
Event-free survival	From randomization (randomized cohorts) or first diagnostic nephrectomy or biopsy (non-randomized cohorts) to the earliest time of relapse, progression, secondary malignancy, or death due to any cause, assessed up to 10 years

Secondary Outcome Measures

Name	Time	Method
Overall survival	From randomization (randomized cohorts) or first diagnostic nephrectomy or biopsy (non-randomized cohorts) to death due to any cause, assessed up to 10 years

Trial Locations

Locations (8): East Carolina University
🇺🇸
Greenville, North Carolina, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸
Las Vegas, Nevada, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸
Toledo, Ohio, United States
Prisma Health Richland Hospital
🇺🇸
Columbia, South Carolina, United States
Dell Children's Medical Center of Central Texas
🇺🇸
Austin, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States

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