Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

Phase 2

Completed

Conditions: Childhood Hepatocellular Carcinoma
Papillary Thyroid Cancer
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Thyroid Cancer
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Recurrent Childhood Liver Cancer
Recurrent Childhood Rhabdomyosarcoma

Interventions: Drug: sorafenib tosylate
Other: pharmacological study
Other: laboratory biomarker analysis

Registration Number: NCT01502410

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial studies how well sorafenib tosylate works in treating younger patients with relapsed or refractory rhabdomyosarcoma, Wilms tumor, liver cancer, or thyroid cancer. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine the objective response rate to sorafenib tosylate (sorafenib) in children with relapsed or refractory rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), or papillary thyroid carcinoma (PTC).

SECONDARY OBJECTIVES:

I. To further define and describe the toxicities of sorafenib administered on an oral, twice-daily continuous schedule.

II. To further characterize the pharmacokinetics of sorafenib in children with refractory cancer.

III. To estimate the progression-free survival on sorafenib for rhabdomyosarcoma, Wilms tumor, and hepatocellular carcinoma and compare to a group of patients enrolled on selected closed Phase II studies of Children Oncology Group (COG).

IV. To assess the biologic activity of sorafenib on vascular endothelial growth factor (VEGF) and soluble vascular endothelial growth factor receptor-2 (VEGFR-2) in peripheral blood samples. (Exploratory) V. To evaluate the presence of BRAF mutations and RET/PTC rearrangements in patients with PTC. (Exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (rhabdomyosarcoma vs Wilms tumor vs hepatocellular carcinoma vs papillary thyroid carcinoma).

Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic studies, and VEGF and VEGFR-2 analysis by ELISA. Previously collected formalin-fixed paraffin-embedded tissue samples, from patients with papillary thyroid carcinoma, are also analyzed for BRAF mutation and RET/PTC rearrangements by PCR.

After completion of study treatment, patients are followed up for up to 5 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:
- Rhabdomyosarcoma (RMS)
- Wilms tumor
- Hepatocellular carcinoma (HCC)
- Papillary thyroid carcinoma (PTC)
Patients must have relapsed or refractory disease (RMS, Wilms tumor, HCC, PTC)
- Patients must have radiographically measurable disease; measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
  - The following do not qualify as measurable disease:
    - Malignant fluid collections (e.g., ascites, pleural effusions)
    - Bone marrow infiltration
    - Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or positron emission tomography [PET] scans)
    - Elevated tumor markers in plasma or cerebrospinal fluid(CSF)
    - Previously radiated lesions that have not demonstrated clear progression post radiation
    - Leptomeningeal lesions that do not meet the requirements noted above
Patients with HCC must be relapsed or refractory to conventional chemotherapy
Patients with PTC must be refractory to radioactive iodine (RAI)
Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Patients with known metastasis to the brain will be excluded from trial participation unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months
Rhabdomyosarcoma and Wilms strata: patients must be ≥ 24 months and ≤ 30 years of age at study enrollment
Hepatocellular carcinoma (HCC): patients must be ≥ 24 months and < 18 years of age at study enrollment
Papillary thyroid carcinoma (PTC): patients must be ≥ 24 months and ≤ 21 years of age at study enrollment
Patients must have a Lansky or Karnofsky performance status score of ≥ 50%, corresponding to ECOG categories 0, 1, or 2
- Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age
- Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
Platelet count ≥ 75,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
Hemoglobin 8.0 g/dL (may receive red blood cell[RBC] transfusions)
Creatinine clearance or radioisotope glomerular filtration rate(GFR) 70 mL/min OR a serum creatinine based on age/gender as follows:
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
SGPT (ALT) ≤ 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
PT, PTT, and INR < 1.5 times ULN
Normal serum lipase and amylase (per institutional normal values)
No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination
A blood pressure (BP) ≤ the 95^th percentile for age, height, and gender; and not receiving medication for treatment of hypertension
Patients who are pregnant or breast-feeding are not eligible
Negative pregnancy tests must be obtained in girls who are post-menarchal
Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of the informed consent until at least 30 days after the last dose of the study drug
Patients with clinical symptoms of hepatic encephalopathy or ascites are not eligible
Patients who have an uncontrolled infection are not eligible
Patients with evidence of bleeding diathesis are not eligible
Patients with known Gilbert syndrome are not eligible
Patients who, in the opinion of the investigator, may not be able to comply with the safety-monitoring requirements of the study are not eligible
No concurrent chemotherapy, radiation therapy, immunomodulating agents, or other investigational agents
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
At least 7 days must have elapsed since the completion of therapy with a growth factor (at least 14 days must have elapsed after receiving pegfilgrastim)
At least 7 days must have elapsed since completion of therapy with a biologic agent;
- For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
At least 2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); ≥ 3 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given
No evidence of active graft-vs-host disease and ≥ 2 months must have elapsed since transplant (stem cell transplant or rescue without total-body irradiation)
For patients with papillary thyroid carcinoma (PTC) only: ≥ 3 weeks from prior radioiodine (RAI) treatment
Patients requiring corticosteroids that have not been on a stable or decreasing dose of corticosteroid for 7 days prior to enrollment are not eligible
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial
Patients who take cytochrome P450 enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, grapefruit juice, or St. Johns wort will not be eligible for the trial
Patients who have received prior treatment with sorafenib are not eligible
Patients must not be on therapeutic anti-coagulation;
- Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial devices is allowed provided that the requirements for prothrombin time(PT), partial thromboplastin time(PTT), and international normalized ratio(INR) are met

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 4 Papillary thyroid carcinoma	sorafenib tosylate	Patients with relapsed or refractory papillary thyroid carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 1 Relapsed/Refractory Rhabdomyosarcoma	sorafenib tosylate	Patients with relapsed or refractory rhabdomyosarcoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 1 Relapsed/Refractory Rhabdomyosarcoma	pharmacological study	Patients with relapsed or refractory rhabdomyosarcoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 1 Relapsed/Refractory Rhabdomyosarcoma	laboratory biomarker analysis	Patients with relapsed or refractory rhabdomyosarcoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 2 Relapsed/Refractory Wilms tumor	sorafenib tosylate	Patients with relapsed or refractory Wilms tumor receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 2 Relapsed/Refractory Wilms tumor	pharmacological study	Patients with relapsed or refractory Wilms tumor receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 2 Relapsed/Refractory Wilms tumor	laboratory biomarker analysis	Patients with relapsed or refractory Wilms tumor receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 3 Relapsed/Refractory hepatocellular carcinoma	sorafenib tosylate	Patients with relapsed or refractory hepatocellular carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 3 Relapsed/Refractory hepatocellular carcinoma	pharmacological study	Patients with relapsed or refractory hepatocellular carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 3 Relapsed/Refractory hepatocellular carcinoma	laboratory biomarker analysis	Patients with relapsed or refractory hepatocellular carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 4 Papillary thyroid carcinoma	pharmacological study	Patients with relapsed or refractory papillary thyroid carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies
Group 4 Papillary thyroid carcinoma	laboratory biomarker analysis	Patients with relapsed or refractory papillary thyroid carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28 pharmacological study: Optional correlative studies laboratory biomarker analysis: Optional correlative studies

Primary Outcome Measures

Name	Time	Method
Objective Response by RECIST Criteria v 1.1	6 cycles (168 days)	Response rates will be calculated as the number of evaluable patients who are responders. Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival According to RECIST Version 1.1	Six months after enrollment	Percent probability of being progression free six months following enrollment. Progression-free interval (PFI) will be calculated as the date of enrollment until the end PFI date, where that date is calculated as the date of disease progression, date of death, date of removal of all tumors by surgery or last patient contact, whichever occurs first.
The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity,	six cycles of chemotherapy; expected to be 126 days of treatment	Each patient is classified as having experienced grade 3 or higher CTC version 4 toxicity if at any time during protocol therapy such an event is observed for the individual.
Pharmacokinetic (PK) Parameters of Sorafenib Tosylate	Prior to administration of Sorafenib (baseline), day 15, day 56, day 112 and day 168	The trough sorafenib concentration is evaluated at baseline (prior to administration of Sorafenib) and 12 hours after administration of Sorafenib on day 15, day 56, day 112 and day 168 in micrograms/ml.
Change in VEGF and VEGFR-2	Prior to the administration of sorafenib (baseline) and day 15 of protocol therapy	Serum VEGF and VEGF receptor 2 Concentration is evaluated at baseline and at day 15 of protocol therapy in picograms/ml.
Presence of BRAF Mutation or RET/PTC Rearrangement	At baseline	Descriptive statistics including mean, median, standard deviation, and range will be calculated for baseline for patients with PTC, TG and TG antibody, and presence of BRAF mutation or RET/PTC rearrangement.

Trial Locations

Locations (92): Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
Nemours Children's Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
University of Hawaii
🇺🇸
Honolulu, Hawaii, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Childrens Hospital of Orange County
🇺🇸
Orange, California, United States
Southern California Permanente Medical Group
🇺🇸
Downey, California, United States
University of Illinois
🇺🇸
Chicago, Illinois, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Childrens Hospital-King's Daughters
🇺🇸
Norfolk, Virginia, United States
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Harvard Cancer Center
🇺🇸
Boston, Massachusetts, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
University of Minnesota Medical Center-Fairview
🇺🇸
Minneapolis, Minnesota, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸
Denver, Colorado, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦
Ste-Foy, Quebec, Canada
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Saint Joseph Children's Hospital of Tampa
🇺🇸
Tampa, Florida, United States
Mark O Hatfield-Warren Grant Magnuson Clinical Center
🇺🇸
Bethesda, Maryland, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Midwest Children's Cancer Center
🇺🇸
Milwaukee, Wisconsin, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Southern Illinois University
🇺🇸
Springfield, Illinois, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Morristown Memorial Hospital
🇺🇸
Morristown, New Jersey, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Medical City Dallas Hospital
🇺🇸
Dallas, Texas, United States
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
Miller Children's Hospital
🇺🇸
Long Beach, California, United States
Nemours Children's Clinic - Orlando
🇺🇸
Orlando, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸
Boise, Idaho, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
The Childrens Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
Washington University School of Medicine
🇺🇸
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
Carolinas Medical Center
🇺🇸
Charlotte, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Greenville Cancer Treatment Center
🇺🇸
Greenville, South Carolina, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Children's Oncology Group
🇺🇸
Philadelphia, Pennsylvania, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Sydney Children's Hospital
🇦🇺
Randwick, New South Wales, Australia
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States