Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

Phase 2

Active, not recruiting

Conditions: Angiomatoid Fibrous Histiocytoma
Epithelioid Sarcoma
Intimal Sarcoma
Malignant Skin Granular Cell Tumor
Malignant Triton Tumor
Undifferentiated High Grade Pleomorphic Sarcoma of Bone
Atypical Fibroxanthoma
Clear Cell Sarcoma of Soft Tissue
Low Grade Myofibroblastic Sarcoma
Myxofibrosarcoma

Interventions: Drug: Pazopanib
Drug: Doxorubicin
Drug: Doxorubicin Hydrochloride
Drug: Ifosfamide
Radiation: Radiation Therapy
Drug: Pazopanib Hydrochloride
Procedure: Therapeutic Conventional Surgery

Registration Number: NCT02180867

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase II/III trial studies how well pazopanib, when combined with chemotherapy and radiation therapy or radiation therapy alone, work in the treatment of patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can eventually be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, 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. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether these therapies can be safely combined and if they work better when given together in treating patients with non-rhabdomyosarcoma soft tissue sarcomas.

Detailed Description: PRIMARY OBJECTIVES:

I. To identify the dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric and adult patients newly diagnosed with unresected intermediate- and high-risk non rhabdomyosarcoma soft tissue sarcomas (NRSTS).

II. To compare the rates of near complete pathologic response (\> 90% necrosis) with the addition of pazopanib to preoperative chemoradiation versus preoperative chemoradiation alone for potentially resectable \> 5 cm, grade 2 or 3 intermediate to high risk chemotherapy-sensitive NRSTS in the phase II portion of the study for this cohort.

III. To compare the rates of near complete pathologic response (\> 90% necrosis) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for potentially resectable intermediate to high risk adult and pediatric NRSTS in the phase II portion of the study for this cohort (using a phase II decision rule to go onto the phase III portion of the study).

IV. To compare the rates of event-free survival (EFS) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for localized intermediate to high risk adult and pediatric NRSTS in the phase III portion of the study for this cohort if the phase II decision rule is passed.

SECONDARY OBJECTIVES:

I. To estimate the rates of local failure, regional failure, distant metastasis free survival, disease-free survival, and overall survival with the addition of pazopanib to preoperative chemoradiation or preoperative radiation in intermediate to high risk adult and pediatric NRSTS.

II. To compare the pattern of recurrence (local, regional and distant) between preoperative chemoradiation or radiation with the addition of pazopanib for adult and pediatric NRSTS.

III. To define the toxicities of ifosfamide and doxorubicin chemotherapy and radiation when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.

IV. To define the toxicities of preoperative radiotherapy when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.

EXPLORATORY OBJECTIVES:

I. To gain insight into the disease biology of childhood and adult NRSTS through analysis of actionable mutations and whole genome sequencing.

II. To determine if microvessel density and circulating tumor deoxyribonucleic acid (DNA) predict response to pazopanib and outcome.

III. To determine the effect of pazopanib on doxorubicin exposure in children and adults with NRSTS.

IV. To evaluate change in fludeoxyglucose F 18 (FDG) positron emission tomography (PET) maximum standard uptake value (SUVmax) from baseline to week 10 or 13 in patients with unresected tumors and to correlate this change with pathologic response and EFS.

V. To compare the rate of response by standard imaging and pathologic assessment to determine which correlates better with local tumor control, distant tumor control, EFS, and overall survival.

OUTLINE: This study starts as a dose-escalation study of pazopanib.

CHEMOTHERAPY COHORT: Patients eligible for chemotherapy cohort are randomized to 1 of 2 treatment regimens.

REGIMEN A:

INDUCTION PHASE: Patients receive pazopanib orally (PO) once daily (QD) on weeks 1-12, ifosfamide intravenously (IV) over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10, and doxorubicin IV over 1-15 minutes on days 1-2 on weeks 1 and 4. At least 24 hours after the completion of week 4 doxorubicin, patients undergo radiation therapy on weeks 4-10.

SURGERY: Patients undergo surgery on week 13.

CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 16-25, ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19, and doxorubicin IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. If applicable, patients undergo additional radiation therapy at week 16

REGIMEN B:

INDUCTION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10 and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 1 and 4. At least 24 hours after the completion of week 4 doxorubicin, patients undergo radiation therapy on weeks 4-10.

SURGERY: Patients undergo surgery on week 13.

CONTINUATION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19 and doxorubicin IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. If applicable, patients undergo additional radiation therapy at week 16.

NON-CHEMOTHERAPY COHORT: Patients eligible for non-chemotherapy cohort are randomized to 1 of 2 treatment regimens.

REGIMEN C:

INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7.

SURGERY: Patients undergo surgery on week 10.

CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.

REGIMEN D:

INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7.

SURGERY: Patients undergo surgery on week 10.

CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.

After completion of study treatment, patients are followed up at 6, 12, 18, 24, 30, 36, 48, and 60 months.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 140

Inclusion Criteria

Note: eligible patients must have a body surface area >= 0.5 m^2 AND be able to swallow whole tablets
Newly diagnosed and histopathologically confirmed, potentially resectable NRSTS of the extremity and trunk will be eligible for the chemotherapy or non-chemotherapy cohort based on:
- Evidence of chemotherapy sensitivity of the histologic sarcoma subtype based on existing evidence from prior clinical trials
- Sufficient risk of metastatic disease to warrant chemotherapy based on size and grade and
- Medically deemed able or unable to undergo chemotherapy
- Notes: an incisional biopsy or core biopsy is preferred; fine needle aspiration biopsy is not acceptable to establish the diagnosis
ELIGIBLE SITES:
- Extremities: upper (including shoulder) and lower (including hip)
- Trunk: body wall
INELIGIBLE SITES: Head and neck, visceral organs (with the exception of embryonal sarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines of the bony pelvis
ELIGIBILITY FOR CHEMOTHERAPY COHORT:
Stage T2a/b (> 5 cm) and grade 2 or 3 AND
One of the following chemosensitive histologies as defined in the World Health Organization (WHO) classification of soft tissue tumors (with some evidence of good response to chemoradiation and of sufficient high risk of metastases, or clear evidence of metastases):
- Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma not otherwise specified [NOS]")
- Synovial sarcoma
- Angiosarcoma of soft tissue
- Adult fibrosarcoma
- Mesenchymal (extraskeletal) chondrosarcoma
- Leiomyosarcoma
- Liposarcoma (excluding myxoid liposarcoma)
- Undifferentiated pleomorphic sarcoma
- Embryonal sarcoma of the liver
Patients meeting the above criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the chemotherapy cohort or the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort
Patients with the following histologies are only eligible for the chemotherapy cohort and cannot enroll on the non-chemotherapy cohort:
- Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma NOS") in patients < 30 years of age
- Synovial sarcoma
- Embryonal sarcoma of the liver
ELIGIBILITY FOR NON-CHEMOTHERAPY COHORT:
Patients with any size of grade 2 or 3 of the following "intermediate (rarely metastasizing)" or "malignant" tumors, as defined in the WHO classification of soft tissue tumors for which we have consensus data of chemotherapy-resistance are eligible only for the non-chemotherapy cohort:
- So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues
- Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma
- Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumor, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), intimal sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor
- Chondro-osseous tumors - extraskeletal osteosarcoma
- Pericytic (perivascular) tumors - malignant glomus tumor
- Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor
- Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
Patients meeting the criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort; note that tumors arising in bone are NOT eligible for this study
Extent of disease:
- Patients with non-metastatic and metastatic disease are eligible
- Initially unresectable patients, with or without metastatic disease, are eligible as long as there is a commitment at enrollment to resect the primary tumor
Sufficient tissue and blood must be available to submit for required biology studies
Lansky performance status score >= 70 for patients =< 16 years of age
Karnofsky performance status score >= 70 for patients > 16 years of age
Absolute neutrophil count >= 1500/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
Platelet count >= 100,000/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
Hemoglobin >= 8 g/dL for patients =< 16 years of age; >= 9 g/dL for patients > 16 years of age; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or normal serum creatinine based on age/gender as follows:
- 2 to < 6 years; 0.8 mg/dL male; 0.8 mg/dL female
- 6 to < 10 years; 1 mg/dL male; 1 mg/dL female
- 10 to < 13 years; 1.2 mg/dL male; 1.2 mg/dL female
- 13 to < 16 years; 1.5 mg/dL male; 1.4 mg/dL female
- >= 16 years; 1.5 mg/dL male; 1.4 mg/dL female
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age
Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by radionuclide angiogram
Corrected QT interval (QTc) < 480 msec
No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading > 94% on room air if there is clinical indication for determination
Patients on low molecular weight heparin or Coumadin (with a stable international normalized ratio [INR]) are eligible
Patient must have a life expectancy of at least 3 months with appropriate therapy
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

Patients with grade 1 NRSTS tumors of any size are not eligible
Patients with known central nervous system (CNS) metastases are not eligible; Note: brain imaging is not an eligibility requirement
Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: patients aged > 17 years with excess of 2.5 mL of hemoptysis are not eligible)
Patients with gross total resection of the primary tumor prior to enrollment on ARST1321 are NOT eligible; patients who have experienced tumor recurrence after a gross total tumor resection are NOT eligible
Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is defined as follows:
- Patients aged =< 17 years: greater than 95th percentile systolic and diastolic blood pressure based on age and height which is not controlled by one anti-hypertensive medication
- Patients aged > 17 years: systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg that is not controlled by one anti-hypertensive medication
Prior Therapy:
- Patients must have had no prior anthracycline (e.g., doxorubicin, daunorubicin) or ifosfamide chemotherapy
- Patients must have had no prior use of pazopanib or similar multi-targeted tyrosine kinase inhibitors (TKI)
- Patients must have had no prior radiotherapy to tumor-involved sites
- Note: patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements; patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded
Other types of invasive malignancy that are not disease free within 3 years except for non-melanoma skin cancer, lentigo maligna, any carcinoma-in-situ or prostate cancer with low risk factors
CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; Note: the use of fentanyl is permitted
CYP3A4 Inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin many non-nucleoside reverse-transcriptase inhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible
CYP3A4 Inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are not eligible (with the exception of glucocorticoids)
Certain medications that are associated with a risk for QTc prolongation and/or Torsades de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible
Subjects with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:
- Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
- Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
- Active peptic ulcer disease
- Malabsorption syndrome
Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:
- Active peptic ulcer disease
- Known intraluminal metastatic lesions
- Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
Subjects with any of the following cardiovascular conditions within the past 6 months
- Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
- Cardiac arrhythmia
- Admission for unstable angina
- Cardiac angioplasty or stenting
- Coronary artery bypass graft surgery
- Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
- Arterial thrombosis
- Symptomatic peripheral vascular disease
- Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
History of serious or non-healing wound, ulcer, or bone fracture
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Patients who are unable to swallow whole tablets are not eligible
Patients with a body surface area < 0.5 m^2 are not eligible
Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib; in addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy
Patients who are receiving any other investigational agent(s)
Pregnancy and breast feeding:
- Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
- Lactating females are not eligible unless they have agreed not to breastfeed their infants during treatment and for a period of 1 month following completion of treatment
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Unwillingness to use an effective contraceptive method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with reproductive potential

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen A (pazopanib, chemoradiation)	Pazopanib Hydrochloride	See Regimen A Detailed Description.
Regimen B (chemoradiation)	Doxorubicin Hydrochloride	See Regimen B Detailed Description.
Regimen B (chemoradiation)	Ifosfamide	See Regimen B Detailed Description.
Regimen C (pazopanib, radiation therapy)	Pazopanib Hydrochloride	INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.
Regimen C (pazopanib, radiation therapy)	Pazopanib	INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.
Regimen B (chemoradiation)	Therapeutic Conventional Surgery	See Regimen B Detailed Description.
Regimen C (pazopanib, radiation therapy)	Radiation Therapy	INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.
Regimen A (pazopanib, chemoradiation)	Radiation Therapy	See Regimen A Detailed Description.
Regimen A (pazopanib, chemoradiation)	Doxorubicin	See Regimen A Detailed Description.
Regimen A (pazopanib, chemoradiation)	Therapeutic Conventional Surgery	See Regimen A Detailed Description.
Regimen B (chemoradiation)	Radiation Therapy	See Regimen B Detailed Description.
Regimen C (pazopanib, radiation therapy)	Therapeutic Conventional Surgery	INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.
Regimen D (radiation therapy)	Radiation Therapy	INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.
Regimen D (radiation therapy)	Therapeutic Conventional Surgery	INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.
Regimen A (pazopanib, chemoradiation)	Doxorubicin Hydrochloride	See Regimen A Detailed Description.
Regimen A (pazopanib, chemoradiation)	Ifosfamide	See Regimen A Detailed Description.
Regimen A (pazopanib, chemoradiation)	Pazopanib	See Regimen A Detailed Description.
Regimen B (chemoradiation)	Doxorubicin	See Regimen B Detailed Description.

Primary Outcome Measures

Name	Time	Method
Feasible Dose: Pediatric	After the first 6 weeks of Induction	The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and \< 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.
Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13	Week 13 after induction	A responder is defined by more than (90% tumor necrosis at week 13). A non-responder has less than 90% necrosis or progressive disease before week 13.
Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10	Week 10 after induction	A responder is defined by more than 90% tumor necrosis at week 10. A non-responder has less than 90% necrosis or progressive disease before week 10.
Percentage of Radiotherapy Patients Failure Free at 5 Years Following Study Entry	From enrollment to up to 60 months	Time to the first occurrence of relapse, progression, secondary cancer or death from any cause.
Feasible Dose: Adult	After the first 6 weeks of Induction	The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in adult unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and \< 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Local Failure Free at 5 Years Following Study Entry	From enrollment to up to 60 months	Defined as disease recurrence only at the primary site of disease at diagnosis. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model. Data were obtained from institutional reported data.
Percentage of Patients Distant Failure Free at 5 Years Following Study Entry	From enrollment to up to 60 months	Defined as disease recurrence at sites other than the primary site and diagnosis and nodes regional to that site (metastatic disease, whether or not present at diagnosis), with or without loco-regional failure. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model. Data were obtained from institutional reported data.
Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)	Reporting of adverse events was required from the start of protocol therapy and until 30 days from the last administration of study drugs; up to 1 year	Participants who experienced Grade 3 or higher toxicity was assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Percentage of Patients Regional Failure Free at 5 Years Following Study Entry	From enrollment to up to 60 months	Defined as disease recurrence at lymph nodes regional to the primary disease site, with or without local failure but without distant failure. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model. Data were obtained from institutional reported data.

Trial Locations

Locations (381): The Kirklin Clinic at Acton Road
🇺🇸
Birmingham, Alabama, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸
Nampa, Idaho, United States
Anchorage Associates in Radiation Medicine
🇺🇸
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸
Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸
Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸
Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Banner Children's at Desert
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Mesa, Arizona, United States
Phoenix Childrens Hospital
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Phoenix, Arizona, United States
Banner University Medical Center - Tucson
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Tucson, Arizona, United States
Arkansas Children's Hospital
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Little Rock, Arkansas, United States
Kaiser Permanente-Anaheim
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Anaheim, California, United States
AIS Cancer Center at San Joaquin Community Hospital
🇺🇸
Bakersfield, California, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸
Burbank, California, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
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Long Beach, California, United States
Children's Hospital Los Angeles
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Los Angeles, California, United States
Kaiser Permanente Los Angeles Medical Center
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Los Angeles, California, United States
Los Angeles General Medical Center
🇺🇸
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
UCLA / Jonsson Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Valley Children's Hospital
🇺🇸
Madera, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸
Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸
Palo Alto, California, United States
Kaiser Permanente-Riverside
🇺🇸
Riverside, California, United States
Sutter Medical Center Sacramento
🇺🇸
Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
Kaiser Permanente-San Diego Zion
🇺🇸
San Diego, California, United States
Rady Children's Hospital - San Diego
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San Diego, California, United States
UCSF Medical Center-Mission Bay
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San Francisco, California, United States
Kaiser Permanente-San Marcos
🇺🇸
San Marcos, California, United States
Kaiser San Rafael-Gallinas
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San Rafael, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸
Torrance, California, United States
Gene Upshaw Memorial Tahoe Forest Cancer Center
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Truckee, California, United States
Children's Hospital Colorado
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Aurora, Colorado, United States
UCHealth University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
UCHealth Memorial Hospital Central
🇺🇸
Colorado Springs, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸
Denver, Colorado, United States
Poudre Valley Hospital
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Fort Collins, Colorado, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
MedStar Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸
Meridian, Idaho, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸
Deerfield Beach, Florida, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville
🇺🇸
Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Nicklaus Children's Hospital
🇺🇸
Miami, Florida, United States
AdventHealth Orlando
🇺🇸
Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸
Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸
Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Saint Mary's Medical Center
🇺🇸
West Palm Beach, Florida, United States
Emory University Hospital Midtown
🇺🇸
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
🇺🇸
Atlanta, Georgia, United States
Augusta University Medical Center
🇺🇸
Augusta, Georgia, United States
Memorial Health University Medical Center
🇺🇸
Savannah, Georgia, United States
Straub Clinic and Hospital
🇺🇸
Honolulu, Hawaii, United States
Kaiser Permanente Moanalua Medical Center
🇺🇸
Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸
Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
🇺🇸
Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸
Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸
Twin Falls, Idaho, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
University of Illinois
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸
Geneva, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
SSM Health Good Samaritan
🇺🇸
Mount Vernon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸
New Lenox, Illinois, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸
Oak Lawn, Illinois, United States
Advocate Children's Hospital-Park Ridge
🇺🇸
Park Ridge, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Saint John's Hospital
🇺🇸
Springfield, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸
Springfield, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸
Warrenville, Illinois, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸
Indianapolis, Indiana, United States
Reid Health
🇺🇸
Richmond, Indiana, United States
Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
🇺🇸
Des Moines, Iowa, United States
Broadlawns Medical Center
🇺🇸
Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, United States
Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Methodist West Hospital
🇺🇸
West Des Moines, Iowa, United States
Newman Regional Health
🇺🇸
Emporia, Kansas, United States
Central Care Cancer Center - Garden City
🇺🇸
Garden City, Kansas, United States
Saint Catherine Hospital
🇺🇸
Garden City, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸
Great Bend, Kansas, United States
Saint Rose Ambulatory and Surgery Center
🇺🇸
Great Bend, Kansas, United States
HaysMed
🇺🇸
Hays, Kansas, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
The University of Kansas Cancer Center - Olathe
🇺🇸
Olathe, Kansas, United States
University of Kansas Cancer Center-Overland Park
🇺🇸
Overland Park, Kansas, United States
Mercy Hospital Pittsburg
🇺🇸
Pittsburg, Kansas, United States
Salina Regional Health Center
🇺🇸
Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus
🇺🇸
Topeka, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸
Westwood, Kansas, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
Norton Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Norton Hospital Pavilion and Medical Campus
🇺🇸
Louisville, Kentucky, United States
Norton Suburban Hospital and Medical Campus
🇺🇸
Louisville, Kentucky, United States
Children's Hospital New Orleans
🇺🇸
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Eastern Maine Medical Center
🇺🇸
Bangor, Maine, United States
Maine Children's Cancer Program
🇺🇸
Scarborough, Maine, United States
Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
🇺🇸
Bethesda, Maryland, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
UMass Memorial Medical Center - University Campus
🇺🇸
Worcester, Massachusetts, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Bronson Battle Creek
🇺🇸
Battle Creek, Michigan, United States
Henry Ford Cancer Institute-Downriver
🇺🇸
Brownstown, Michigan, United States
Henry Ford Macomb Hospital-Clinton Township
🇺🇸
Clinton Township, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Henry Ford Health Saint John Hospital
🇺🇸
Detroit, Michigan, United States
Michigan State University Clinical Center
🇺🇸
East Lansing, Michigan, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸
Grand Rapids, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸
Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸
Grand Rapids, Michigan, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Ascension Borgess Hospital
🇺🇸
Kalamazoo, Michigan, United States
University of Michigan Health - Sparrow Lansing
🇺🇸
Lansing, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸
Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸
Niles, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸
Reed City, Michigan, United States
Corewell Health Children's
🇺🇸
Royal Oak, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸
Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸
Saint Joseph, Michigan, United States
Munson Medical Center
🇺🇸
Traverse City, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸
West Bloomfield, Michigan, United States
Essentia Health Cancer Center
🇺🇸
Duluth, Minnesota, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸
Rochester, Minnesota, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Central Care Cancer Center - Bolivar
🇺🇸
Bolivar, Missouri, United States
University of Missouri Children's Hospital
🇺🇸
Columbia, Missouri, United States
Siteman Cancer Center at West County Hospital
🇺🇸
Creve Coeur, Missouri, United States
Freeman Health System
🇺🇸
Joplin, Missouri, United States
Children's Mercy Hospitals and Clinics
🇺🇸
Kansas City, Missouri, United States
The University of Kansas Cancer Center-South
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
University of Kansas Cancer Center - North
🇺🇸
Kansas City, Missouri, United States
University of Kansas Cancer Center - Lee's Summit
🇺🇸
Lee's Summit, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸
Rolla, Missouri, United States
Phelps Health Delbert Day Cancer Institute
🇺🇸
Rolla, Missouri, United States
Cardinal Glennon Children's Medical Center
🇺🇸
Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Radiation Oncology Centers of Nevada Central
🇺🇸
Las Vegas, Nevada, United States
GenesisCare USA - Las Vegas
🇺🇸
Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸
Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Las Vegas, Nevada, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
Saint Mary's Regional Medical Center
🇺🇸
Reno, Nevada, United States
Radiation Oncology Associates
🇺🇸
Reno, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸
Lebanon, New Hampshire, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
Saint Peter's University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸
Newark, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸
Paterson, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
Montefiore Medical Center-Einstein Campus
🇺🇸
Bronx, New York, United States
Montefiore Medical Center-Weiler Hospital
🇺🇸
Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Glens Falls Hospital
🇺🇸
Glens Falls, New York, United States
NYU Langone Hospital - Long Island
🇺🇸
Mineola, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸
New Hyde Park, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸
New York, New York, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸
New York, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
Mission Hospital
🇺🇸
Asheville, North Carolina, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
East Carolina University
🇺🇸
Greenville, North Carolina, United States
Matthews Radiation Oncology Center
🇺🇸
Matthews, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center
🇺🇸
Fargo, North Dakota, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Miami Valley Hospital North
🇺🇸
Dayton, Ohio, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸
Beachwood, Ohio, United States
Indu and Raj Soin Medical Center
🇺🇸
Beavercreek, Ohio, United States
Dayton Physicians LLC-Miami Valley South
🇺🇸
Centerville, Ohio, United States
Miami Valley Hospital South
🇺🇸
Centerville, Ohio, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Kenwood
🇺🇸
Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Blue Ash
🇺🇸
Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Dayton Physician LLC - Englewood
🇺🇸
Dayton, Ohio, United States
Armes Family Cancer Center
🇺🇸
Findlay, Ohio, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
Orion Cancer Care
🇺🇸
Findlay, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Dayton Physicians LLC-Atrium
🇺🇸
Franklin, Ohio, United States
Dayton Physicians LLC-Wayne
🇺🇸
Greenville, Ohio, United States
Wayne Hospital
🇺🇸
Greenville, Ohio, United States
Greater Dayton Cancer Center
🇺🇸
Kettering, Ohio, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Springfield Regional Cancer Center
🇺🇸
Springfield, Ohio, United States
Springfield Regional Medical Center
🇺🇸
Springfield, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸
Toledo, Ohio, United States
Dayton Physicians LLC - Troy
🇺🇸
Troy, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Wright-Patterson Medical Center
🇺🇸
Wright-Patterson Air Force Base, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Mercy Hospital Oklahoma City
🇺🇸
Oklahoma City, Oklahoma, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸
Tulsa, Oklahoma, United States
Saint Charles Health System
🇺🇸
Bend, Oregon, United States
Clackamas Radiation Oncology Center
🇺🇸
Clackamas, Oregon, United States
Bay Area Hospital
🇺🇸
Coos Bay, Oregon, United States
Providence Portland Medical Center
🇺🇸
Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸
Portland, Oregon, United States
Legacy Emanuel Children's Hospital
🇺🇸
Portland, Oregon, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Drexel University School of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
🇺🇸
Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Lankenau Medical Center
🇺🇸
Wynnewood, Pennsylvania, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸
Boiling Springs, South Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Prisma Health Richland Hospital
🇺🇸
Columbia, South Carolina, United States
Greenville Health System Cancer Institute-Andrews
🇺🇸
Greenville, South Carolina, United States
Saint Francis Hospital
🇺🇸
Greenville, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
Prisma Health Cancer Institute - Butternut
🇺🇸
Greenville, South Carolina, United States
Prisma Health Cancer Institute - Faris
🇺🇸
Greenville, South Carolina, United States
Prisma Health Greenville Memorial Hospital
🇺🇸
Greenville, South Carolina, United States
Saint Francis Cancer Center
🇺🇸
Greenville, South Carolina, United States
Prisma Health Cancer Institute - Eastside
🇺🇸
Greenville, South Carolina, United States
Prisma Health Cancer Institute - Greer
🇺🇸
Greer, South Carolina, United States
Prisma Health Cancer Institute - Seneca
🇺🇸
Seneca, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸
Sioux Falls, South Dakota, United States
T C Thompson Children's Hospital
🇺🇸
Chattanooga, Tennessee, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial
🇺🇸
Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
🇺🇸
Austin, Texas, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸
Dallas, Texas, United States
Parkland Memorial Hospital
🇺🇸
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
El Paso Children's Hospital
🇺🇸
El Paso, Texas, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Covenant Children's Hospital
🇺🇸
Lubbock, Texas, United States
UMC Cancer Center / UMC Health System
🇺🇸
Lubbock, Texas, United States
Texas Tech University Health Sciences Center-Lubbock
🇺🇸
Lubbock, Texas, United States
Children's Hospital of San Antonio
🇺🇸
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Scott and White Memorial Hospital
🇺🇸
Temple, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
South Jordan Health Center
🇺🇸
South Jordan, Utah, United States
Central Vermont Medical Center/National Life Cancer Treatment
🇺🇸
Berlin, Vermont, United States
University of Vermont Medical Center
🇺🇸
Burlington, Vermont, United States
University of Vermont and State Agricultural College
🇺🇸
Burlington, Vermont, United States
University of Virginia Cancer Center
🇺🇸
Charlottesville, Virginia, United States
Inova Fairfax Hospital
🇺🇸
Falls Church, Virginia, United States
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
Carilion Children's
🇺🇸
Roanoke, Virginia, United States
Providence Regional Cancer System-Aberdeen
🇺🇸
Aberdeen, Washington, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸
Bellingham, Washington, United States
Providence Regional Cancer System-Centralia
🇺🇸
Centralia, Washington, United States
Providence Regional Cancer Partnership
🇺🇸
Everett, Washington, United States
Swedish Cancer Institute-Issaquah
🇺🇸
Issaquah, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸
Kennewick, Washington, United States
Providence Regional Cancer System-Lacey
🇺🇸
Lacey, Washington, United States
PeaceHealth Saint John Medical Center
🇺🇸
Longview, Washington, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Swedish Medical Center-Ballard Campus
🇺🇸
Seattle, Washington, United States
Kaiser Permanente Washington
🇺🇸
Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Madigan Army Medical Center
🇺🇸
Tacoma, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸
Vancouver, Washington, United States
Providence Saint Mary Regional Cancer Center
🇺🇸
Walla Walla, Washington, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸
Yakima, Washington, United States
West Virginia University Charleston Division
🇺🇸
Charleston, West Virginia, United States
West Virginia University Healthcare
🇺🇸
Morgantown, West Virginia, United States
Aurora Cancer Care-Southern Lakes VLCC
🇺🇸
Burlington, Wisconsin, United States
Aurora Health Center-Fond du Lac
🇺🇸
Fond Du Lac, Wisconsin, United States
Aurora Health Care Germantown Health Center
🇺🇸
Germantown, Wisconsin, United States
Aurora Cancer Care-Grafton
🇺🇸
Grafton, Wisconsin, United States
Aurora BayCare Medical Center
🇺🇸
Green Bay, Wisconsin, United States
Aurora Cancer Care-Kenosha South
🇺🇸
Kenosha, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸
Madison, Wisconsin, United States
Aurora Bay Area Medical Group-Marinette
🇺🇸
Marinette, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸
Marshfield, Wisconsin, United States
Aurora Cancer Care-Milwaukee
🇺🇸
Milwaukee, Wisconsin, United States
Aurora Saint Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Aurora Sinai Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Vince Lombardi Cancer Clinic - Oshkosh
🇺🇸
Oshkosh, Wisconsin, United States
Aurora Cancer Care-Racine
🇺🇸
Racine, Wisconsin, United States
Vince Lombardi Cancer Clinic-Sheboygan
🇺🇸
Sheboygan, Wisconsin, United States
Aurora Medical Center in Summit
🇺🇸
Summit, Wisconsin, United States
Vince Lombardi Cancer Clinic-Two Rivers
🇺🇸
Two Rivers, Wisconsin, United States
Aurora Cancer Care-Waukesha
🇺🇸
Waukesha, Wisconsin, United States
Aurora Cancer Care-Milwaukee West
🇺🇸
Wauwatosa, Wisconsin, United States
Aurora West Allis Medical Center
🇺🇸
West Allis, Wisconsin, United States
Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Janeway Child Health Centre
🇨🇦
Saint John's, Newfoundland and Labrador, Canada
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
Children's Hospital
🇨🇦
London, Ontario, Canada
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
CIUSSSEMTL-Hopital Maisonneuve-Rosemont
🇨🇦
Montreal, Quebec, Canada
CHUM - Centre Hospitalier de l'Universite de Montreal
🇨🇦
Montreal, Quebec, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Allan Blair Cancer Centre
🇨🇦
Regina, Saskatchewan, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
🇨🇦
Quebec, Canada
San Jorge Children's Hospital
🇵🇷
San Juan, Puerto Rico
University Pediatric Hospital
🇵🇷
San Juan, Puerto Rico