Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients
Overview
- Phase
- Phase 3
- Intervention
- Biospecimen Collection
- Conditions
- Anaplastic Medulloblastoma
- Sponsor
- Children's Oncology Group
- Enrollment
- 379
- Locations
- 185
- Primary Endpoint
- Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.
Detailed Description
PRIMARY OBJECTIVES: I. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/primitive neuroectodermal tumor (PNET) patients. II. To determine whether isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients. SECONDARY OBJECTIVES: I. To compare residual disease response to radiation alone versus radiation plus carboplatin. II. To identify molecular prognostic indicators suitable for patient stratification in future trials. III. To evaluate the health-related quality of life (HRQOL) during phases of active treatment specific to treatment modalities. IV. To describe the neuropsychological functioning of the study population and to evaluate the relationship between neuropsychological status and health related quality of life. OUTLINE: Patients are randomized to Arm A or Arm B (Arms C and D closed to accrual as of Amendment 3 1/27/15). ARM A (standard chemoradiotherapy and standard maintenance therapy): CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD) five days a week for 6 weeks. Patients also receive vincristine sulfate intravenously (IV) over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim subcutaneously (SC) or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. ARM B (standard chemoradiotherapy plus carboplatin and standard maintenance therapy): CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm I. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm I. ARM C (standard chemoradiotherapy, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin - CLOSED TO ACCRUAL 1/27/15): CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin orally (PO) twice daily (BID) on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm I maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ARM D (standard chemoradiotherapy plus carboplatin, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin - CLOSED TO ACCRUAL 1/27/15): CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm II. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm III. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm III. After completion of study treatment, patients are followed up periodically for 1 year.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Newly diagnosed, previously untreated: (1) M0 medulloblastoma with \> 1.5 cm\^2 residual; (2) M+ medulloblastoma; patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor
- •As of amendment # 2, enrollment of patients with supratentorial PNET has been discontinued
- •All patients with M4 disease are not eligible
- •A pre-operative magnetic resonance imaging (MRI) scan of the brain with and without contrast is required; NOTE: computed tomography (CT) scans are NOT sufficient for study eligibility
- •Post-operative head MRI scan with and without contrast (preferably within 72 hours post-surgery); for patients who undergo stereotactic biopsy only, either a pre or post-operative MRI is sufficient; for patients with M2 and M3 disease, a post-op MRI is strongly encouraged, but not mandatory
- •Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done pre-operatively or within 28 days of surgery if done post-operatively; for posterior fossa tumors, pre-operative MRI scans are preferred
- •Lumbar cerebrospinal fluid (CSF) cytology examination must be obtained pre-operatively or within 31 days following surgery; the optimal time for obtaining CSF is prior to surgery or 1-3 weeks following surgery; ventricular CSF (either pre- or post-op) may be used only if a post-operative spinal tap is contraindicated; if a spinal tap is contraindicated and there is no ventricular CSF available, then CSF cytology can be waived for patients with supratentorial tumors or if there is documentation of spinal subarachnoid metastases (M3); patients who are categorized as M1 must have either an intra-operative positive CSF (via lumbar puncture at the end of the procedure) or a positive lumbar CSF obtained \> 7 days post-operatively
- •Patients must have a Karnofsky performance level of \>= 30 for patients \> 16 years of age or a Lansky performance scale of \>= 30 for patients =\< 16 years of age and life expectancy \> 8 weeks
- •No previous chemotherapy or radiation therapy
- •Corticosteroids should not be used during chemotherapy administration as an antiemetic
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Biospecimen Collection
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Cisplatin
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Cyclophosphamide
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Filgrastim
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Lumbar Puncture
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Magnetic Resonance Imaging
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Quality-of-Life Assessment
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Radiation Therapy
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Vincristine Sulfate
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Biospecimen Collection
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Carboplatin
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Cisplatin
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Cyclophosphamide
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Filgrastim
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Lumbar Puncture
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Magnetic Resonance Imaging
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Quality-of-Life Assessment
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Radiation Therapy
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
Intervention: Vincristine Sulfate
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Cyclophosphamide
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Filgrastim
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Isotretinoin
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Radiation Therapy
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Vincristine Sulfate
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Carboplatin
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Cisplatin
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Cyclophosphamide
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Filgrastim
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Isotretinoin
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Quality-of-Life Assessment
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Radiation Therapy
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
Intervention: Vincristine Sulfate
Outcomes
Primary Outcomes
Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
Time Frame: Up to 5 years
The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Time Frame: Up to 5 years
The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals.
Secondary Outcomes
- Tumor Response to Radiation Therapy for Patients With Medulloblastoma(12 weeks after treatment initiation)
- Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)(12 weeks after treatment initiation)
- Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma(Up to 5 years)
- Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)(Up to 5 years)
- The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients(6 - 12 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients(24 - 36 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients(48 - 72 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients(6 - 12 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients(24 - 36 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients(48 - 72 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients(6 - 12 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients(24 - 36 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients(48 - 72 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients(6 - 12 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients(24 - 36 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients(48 - 72 months post diagnosis)