Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma

Phase 2

Completed

Conditions: Untreated Childhood Rhabdomyosarcoma
Childhood Alveolar Rhabdomyosarcoma
Childhood Embryonal Rhabdomyosarcoma
Adult Rhabdomyosarcoma
Metastatic Childhood Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma

Interventions: Biological: Cixutumumab
Biological: Dactinomycin
Drug: Cyclophosphamide
Drug: Etoposide
Drug: Doxorubicin Hydrochloride
Drug: Ifosfamide
Drug: Irinotecan Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Temozolomide
Drug: Vincristine Sulfate Liposome

Registration Number: NCT01055314

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized pilot clinical trial is studying the side effects and how well giving temozolomide and cixutumumab together with combination chemotherapy works in treating patients with metastatic rhabdomyosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving temozolomide and cixutumumab together with combination chemotherapy may kill more tumor cells.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine the feasibility of administering IMC-A12 (cixutumumab) in combination with a multi-agent intensive chemotherapy regimen for the treatment of high-risk rhabdomyosarcoma (RMS).

II. To determine the feasibility of adding temozolomide to vincristine (vincristine sulfate)/irinotecan (irinotecan hydrochloride) cycles in patients with high-risk RMS.

III. To assess immediate and short-term side effects of delivery of concurrent temozolomide-vincristine-irinotecan with irradiation in patients with high-risk RMS.

SECONDARY OBJECTIVES:

I. To gain a preliminary estimate of the response rate to IMC-A12 or temozolomide plus vincristine/irinotecan in previously untreated high-risk RMS.

II. To obtain preliminary efficacy data for IMC-A12 or temozolomide in combination with a multi-agent interval compressed chemotherapy regimen in previously untreated high-risk RMS.

III. To determine the effectiveness of detecting metastatic disease with fludeoxyglucose F 18 positron emission tomography (FDG PET) and to compare assessment of response using standard imaging techniques with response assessed by FDG PET.

IV. To assess changes in serum levels of insulin-like growth factor (IGF)-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR inhibition.

OUTLINE: This is a dose-escalation study of cixutumumab. Patients are assigned to 1 of 2 treatment groups according to the timing of their enrollment onto the study.

GROUP 1: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy\* on days 1-5 of weeks 20-24.

GROUP 2: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy\* as in group 1. Patients also receive temozolomide orally (PO) on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.

GROUP 3: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and undergo radiation therapy\* as in group 1. Patients also receive temozolomide as in group 2. (Discontinued as of January 2013)

NOTE: \*Patients with parameningeal tumors and evidence of intracranial extension or those requiring emergency radiotherapy may receive radiation therapy starting in week 1; cixutumumab should be withheld during radiation therapy.

After completion of study therapy, patients are followed up at 3 weeks and then periodically for up to 5 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 175

Inclusion Criteria

Patients must be eligible for, and enrolled on D9902 prior to enrollment on ARST08P1
Patients with newly diagnosed, biopsy-proven metastatic rhabdomyosarcoma or ectomesenchymoma (stage IV, clinical group IV) are eligible for this study; patients with stage IV, clinical group IV RMS with parameningeal and paraspinal primary tumors, including those with intracranial extension (ICE) are eligible for ARST08P1; ICE is defined by contrast magnetic resonance imaging (MRI) showing that the primary tumor touches, displaces, invades, distorts, or otherwise causes signal abnormality of the dura in brain or spinal cord in contiguity to the primary site; ICE is also presumed to exist if the cerebrospinal fluid (CSF) cytopathology is positive for tumor at diagnosis
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
No prior chemotherapy or radiotherapy except for use of corticosteroids or emergent radiation therapy; patients requiring emergency radiation are eligible
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73m^2 OR maximum serum creatinine based on age/gender as follows:
- 0.4 mg/dL (for patients 1 to 5 months of age)
- 0.5 mg/dL (for patients 6 to 11 months of age)
- 0.6 mg/dL (for patients 1 year of age)
- 0.8 mg/dL (for patients 2 to 5 years of age)
- 1.0 mg/dL (for patients 6 to 9 years of age)
- 1.2 mg/dL (for patients 10 to 12 years of age)
- 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
- 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)
Patients with urinary tract obstruction by tumor must meet the renal function criteria listed above AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, unless there is evidence of biliary obstruction by the tumor
Shortening fraction >= 27% by echocardiogram (ECHO) OR ejection fraction >= 50% by radionuclide angiogram
Absolute neutrophil count (ANC) >= 750/uL; abnormal blood counts are permissible if there is bone marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma
Platelet count >= 75,000/uL; abnormal blood counts are permissible if there is bone marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma
Sexually active patients of childbearing potential must agree to use effective contraception during therapy (Pilots 1 and 2) and for at least 3 months after the last dose of IMC-A12 (Pilots 1)

Exclusion Criteria

Female patients who are pregnant are not eligible
Female patients who are breastfeeding are not eligible; female patients who are lactating must agree to stop breastfeeding to participate in this study
Patients receiving growth hormone therapy are not eligible
Patients with known type I or type II diabetes mellitus are not eligible for enrollment on Pilot 1
Patients with evidence of uncontrolled infection are not eligible
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Cixutumumab	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Laboratory Biomarker Analysis	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Dactinomycin	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Etoposide	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Laboratory Biomarker Analysis	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Dactinomycin	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Vincristine Sulfate Liposome	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Temozolomide	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Vincristine Sulfate Liposome	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Cyclophosphamide	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Doxorubicin Hydrochloride	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Etoposide	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Irinotecan Hydrochloride	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 1 (chemotherapy, radiation therapy, cixutumumab)	Ifosfamide	Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Cyclophosphamide	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Doxorubicin Hydrochloride	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Irinotecan Hydrochloride	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
Group 2 (chemotherapy, radiation therapy, temozolomide)	Ifosfamide	Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.

Primary Outcome Measures

Name	Time	Method
Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment	From start to week 26 of therapy	Proportion of no Grade 3+ cardiac toxicity.
Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0	Up to 54 weeks	Number of patients with grade 3+ adverse events (AE) during therapy. (Grade 3+) = (Grade 3 + Grade 4 + Grade 5) . Grade 3: Severe and undesirable AE; Grade 4: Life threatening or disabling AE; Grade 5: Death related to AE.
Event-Free Survival	3 years	Probability of no relapse, secondary malignancy, or death after 3 years in the study.
Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment	From start to week 26 of therapy	Proportion of no Grade 4+ non-hematologic toxicity.

Secondary Outcome Measures

Name	Time	Method
Response Rate (CR + PR)	From the start of treatment until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities	Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at \> 4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment; Overall Response (OR) = CR + PR.

Trial Locations

Locations (139): Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Nevada Cancer Research Foundation CCOP
🇺🇸
Las Vegas, Nevada, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
David Geffen School of Medicine at UCLA
🇺🇸
Los Angeles, California, United States
Southern California Permanente Medical Group
🇺🇸
Downey, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸
Long Beach, California, United States
Childrens Hospital of Orange County
🇺🇸
Orange, California, United States
Mattel Children's Hospital UCLA
🇺🇸
Los Angeles, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸
Oakland, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
University of New Mexico
🇺🇸
Albuquerque, New Mexico, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸
New Hyde Park, New York, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Royal Children's Hospital-Brisbane
🇦🇺
Herston, Queensland, Australia
Albany Medical Center
🇺🇸
Albany, New York, United States
Saint Joseph's Regional Medical Center
🇺🇸
Paterson, New Jersey, United States
Morristown Memorial Hospital
🇺🇸
Morristown, New Jersey, United States
New York University Langone Medical Center
🇺🇸
New York, New York, United States
Carolinas Medical Center
🇺🇸
Charlotte, North Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Starship Children's Hospital
🇳🇿
Grafton, Auckland, New Zealand
Royal Brisbane and Women's Hospital
🇦🇺
Herston, Queensland, Australia
Penn State Hershey Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
West Virginia University Charleston
🇺🇸
Charleston, West Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
University of Rochester
🇺🇸
Rochester, New York, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Phoenix Childrens Hospital
🇺🇸
Phoenix, Arizona, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Chedoke-McMaster Hospitals
🇨🇦
Hamilton, Ontario, Canada
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦
Quebec, Canada
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Midwest Children's Cancer Center
🇺🇸
Milwaukee, Wisconsin, United States
The Children's Hospital at Westmead
🇦🇺
Westmead, New South Wales, Australia
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Mercy Children's Hospital
🇺🇸
Toledo, Ohio, United States
Legacy Emanuel Children's Hospital
🇺🇸
Portland, Oregon, United States
Legacy Emanuel Hospital and Health Center
🇺🇸
Portland, Oregon, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Medical City Dallas Hospital
🇺🇸
Dallas, Texas, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Childrens Hospital-King's Daughters
🇺🇸
Norfolk, Virginia, United States
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Sydney Children's Hospital
🇦🇺
Randwick, New South Wales, Australia
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸
Tulsa, Oklahoma, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸
Denver, Colorado, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Broward Health Medical Center
🇺🇸
Fort Lauderdale, Florida, United States
MedStar Georgetown University Hospital
🇺🇸
Washington, D.C., District of Columbia, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
Memorial Healthcare System - Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
Children's National Medical Center
🇺🇸
Washington, D.C., District of Columbia, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸
Tampa, Florida, United States
Saint Mary's Hospital
🇺🇸
West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸
Boise, Idaho, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Southern Illinois University
🇺🇸
Springfield, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
Children's Hospital New Orleans
🇺🇸
New Orleans, Louisiana, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
🇺🇸
Bethesda, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Kalamazoo Center for Medical Studies
🇺🇸
Kalamazoo, Michigan, United States
The Childrens Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
University of Minnesota Medical Center-Fairview
🇺🇸
Minneapolis, Minnesota, United States
Cardinal Glennon Children's Medical Center
🇺🇸
Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Saint John's Mercy Medical Center
🇺🇸
Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
UMDNJ - Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Newark Beth Israel Medical Center
🇺🇸
Newark, New Jersey, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸
Tacoma, Washington, United States
Alberta Children's Hospital
🇨🇦
Calgary, Alberta, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
Children's Hospital of Eastern Ontario
🇨🇦
Ottawa, Ontario, Canada
Yale University
🇺🇸
New Haven, Connecticut, United States
Nemours Children's Hospital
🇺🇸
Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Greenville Cancer Treatment Center
🇺🇸
Greenville, South Carolina, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
St. Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
University of Vermont College of Medicine
🇺🇸
Burlington, Vermont, United States
Palmetto Health Richland
🇺🇸
Columbia, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸
Sioux Falls, South Dakota, United States
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Saskatoon Cancer Centre
🇨🇦
Saskatoon, Saskatchewan, Canada
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States