Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

Phase 2

Active, not recruiting

Conditions: Recurrent Adrenal Cortical Carcinoma
Recurrent Clear Cell Sarcoma of Soft Tissue
Recurrent Ewing Sarcoma
Recurrent Osteosarcoma
Recurrent Primary Malignant Central Nervous System Neoplasm
Recurrent Renal Cell Carcinoma
Refractory Malignant Solid Neoplasm
Refractory Wilms Tumor
Alveolar Soft Part Sarcoma
Central Nervous System Neoplasm

Interventions: Drug: Cabozantinib
Drug: Cabozantinib S-malate
Other: Pharmacological Study

Registration Number: NCT02867592

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial studies how well cabozantinib-s-malate works in treating younger patients with sarcomas, Wilms tumor, or other rare tumors that have come back, do not respond to therapy, or are newly diagnosed. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth and tumor blood vessel growth.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine the objective response rate (complete response + partial response) of cabozantinib-s-malate (XL184) in children and young adults with Ewing sarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, and Wilms tumor.

II. To estimate whether XL184 therapy either improves the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to a historical Childrens Oncology Group (COG) experience or produces an objective response rate.

SECONDARY OBJECTIVES:

I. To further define XL184 related toxicities in pediatric, adolescent and young adult patients.

II. To further define XL184 pharmacokinetics in the pediatric and adolescent patients.

III. To estimate 1-year time to progression, progression free survival (PFS) and overall survival for each stratum, and if feasible to compare to historical controls.

EXPLORATORY OBJECTIVES:

I. To assess the effect of XL184 on patients' immune cell subsets. II. To obtain tumor tissue (snap frozen, formalin-fixed and paraffin-embedded \[FFPE\] blocks, or unstained slides) from diagnosis, recurrence, or both, for possible future studies.

OUTLINE:

Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 6 months for 1 year and then annually for up to 5 years.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 109

Inclusion Criteria

Upper age limit of =< 18 years of age for medullary thyroid carcinoma (MTC), renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) =< 30 years for all other diagnoses
Patients must have a body surface area >= 0.35 m^2
Patients must have recurrent or refractory disease, or newly diagnosed disease with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:
- Ewing sarcoma
- Rhabdomyosarcoma (RMS)
- Non-rhabdomyosarcoma soft tissue sarcomas (STS) including microphthalmia transcription factor associated STS (alveolar soft part sarcoma [ASPS] and clear cell sarcoma [CCS])
- Osteosarcoma
- Wilms tumor
- Rare tumors
  - Medullary thyroid carcinoma (MTC)
  - Renal cell carcinoma (RCC)
  - Hepatocellular carcinoma (HCC)
  - Hepatoblastoma
  - Adrenal coertex carcinoma
  - Pediatric solid tumors (including central nervous system [CNS] tumors) with known molecular alterations in the targets of XL184 (i.e., MET amplification, overexpression, activating mutation, MET translocation, MET exon skipping mutations, activating RET mutations, RET rearrangement, overexpression or activation of AXL); documentation of the alteration from a Clinical Laboratory Improvement Act (CLIA) certified laboratory will be required
    - Note: Documentation of any known tumor molecular alterations and RET mutation status for patients with MTC (germline) must be uploaded via the RAVE system
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)
- Note: 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 measurement parameters noted above
Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (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
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
Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
>= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of M-Iodobenzylguanidine (MIBG); >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total-body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
- Subjects should not have any clinically relevant ongoing complications from prior radiation therapy (i.e., radiation esophagitis or other inflammation of the viscera)
No evidence of active graft versus (vs.) host disease and >= 2 months must have elapsed since transplant
Not previously received XL184 or another MET/HGF inhibitor (tivantinib or crizotinib); there are no limits on number of prior therapeutic regimens; patients who have been treated with prior VEGF pathway, or RET inhibitors (except XL184) may be eligible
Peripheral absolute neutrophil count (ANC) >= 1000/uL for patients with solid tumors without bone marrow involvement
Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment) for patients with solid tumors without bone marrow involvement
Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) for patients with solid tumors without bone marrow involvement
Peripheral absolute neutrophil count (ANC) >= 750/uL for patients with solid tumors and known bone marrow metastatic disease
Platelet count >= 50,000/uL for patients with solid tumors and known bone marrow metastatic disease
Hemoglobin >= 8.0 g/dL for patients with solid tumors and known bone marrow metastatic disease
Transfusions are permitted to meet both the platelet and hemoglobin criteria for patients with known bone marrow metastatic disease; patients must not be known to be refractory to red blood cell or platelet transfusions
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- 2 to < 6 years of age
  - Male and female: 0.8 (maximum serum creatinine [mg/dL])
- 6 to < 10 years of age
  - Male and female: 1 (maximum serum creatinine [mg/dL])
- 10 to < 13 years of age
  - Male and female: 1.2 (maximum serum creatinine [mg/dL])
- 13 to < 16 years of age
  - Male 1.5 (maximum serum creatinine [mg/dL])
  - Female: 1.4 (maximum serum creatinine [mg/dL])
- >= 16 years of age
  - Male: 1.7 (maximum serum creatinine [mg/dL])
  - Female: 1.4 (maximum serum creatinine [mg/dL])
Urine protein: =< 30 mg/dl in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour (h) urine sample
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3 x ULN) (for the purpose of this study, the ULN for SGPT is 45 U/L)
Serum albumin >= 2.8 g/dL
No history of congenital prolonged corrected QT (QTc) syndrome, New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)
No clinically significant cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to enrollment
QTc =< 480 msec; Note: Patients with grade 1 prolonged QTc (450- 480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)
Patients with a known seizure disorder who are receiving non-enzyme inducing anticonvulsants and have well-controlled seizures may be enrolled
CNS toxicity =< grade 2 with the exception of decreased tendon reflex (DTR); any grade of DTR is eligible
A blood pressure (BP) =< the 95th percentile for age, height, and gender for pediatric patients < 18 years old and =< 140/90 mmHg for patients >= 18 years old; patients should not be receiving medication for treatment of hypertension (except patients with Wilms tumor and RCC who may be eligible if on stable doses of no more than one anti-hypertensive medication with a baseline BP =< ULN for pediatric patients and =< 140/90 for adult patients); please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP
International normalized ratio (INR) =< 1.5
Serum amylase =< 1.5 x ULN
Serum lipase =< 1.5 x ULN

Exclusion Criteria

Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; 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 two methods of birth control- a medically accepted barrier method of contraceptive method (e.g., male or female condom) and a second effective method of birth control-during protocol therapy and for at least 4 months after the last dose of XL184; abstinence is an acceptable method of birth control
Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)
Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Previous treatment with XL184 (cabozantinib) or another MET/HGF inhibitor (tivantinib, crizotinib)
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 must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort
Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin, and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) are prohibited
- Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted; anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen
Patients must not have received enzyme-inducing anticonvulsants within 14 days prior to enrollment
Patients who are receiving drugs that prolong QTc are not eligible
Patients who are unable to swallow intact tablets are not eligible
Patients who have an uncontrolled infection 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
Patients with active bleeding are not eligible; specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment; patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with evidence of resolving hemorrhage will be eligible); in patients with CNS tumors, an MRI with ECHO gradient sequences would be required to exclude presence of petechial hemorrhages
Patients who have had or are planning to have the following invasive procedures are not eligible:
- Major surgical procedure, laparoscopic procedure, or open biopsy within 28 days prior to enrollment
- Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g., Hickman or Broviac catheter, peripherally inserted central catheter [PICC]) and at least 7 days prior to enrollment for a subcutaneous port
- Core biopsy within 7 days prior to enrollment
- Fine needle aspirate within 7 days prior to enrollment
- Surgical or other wounds must be adequately healed prior to enrollment
- NOTE: For purposes of this study, bone marrow aspirate and biopsy are not considered surgical procedures and therefore are permitted within 14 days prior to start of protocol therapy
Patients who have had significant traumatic injury within 28 days prior to enrollment are not eligible
Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of the study drug are not eligible

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (cabozantinib s-malate)	Cabozantinib S-malate	Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (cabozantinib s-malate)	Pharmacological Study	Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (cabozantinib s-malate)	Cabozantinib	Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Objective Response (Non-Osteosarcoma Strata)	Up to the first 6 cycles of therapy	Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Response rates will be calculated as the percent of evaluable patients who are responders (Overall Best Response of Partial Response or Complete Response), and confidence intervals will be constructed accounting for the two-stage design.
Objective Response (Osteosarcoma Stratum)	Up to the first 6 cycles of therapy.	Will be assessed by the Response Evaluation Criteria in Solid Tumors version 1.1 and Disease Control (see section 9.3.2 of the ADVL1622 Protocol). Response + Disease Control rate will be calculated as the percent of evaluable patients who are responders or who met the definition of disease control, and confidence intervals will be constructed accounting for the two-stage design.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Cmax	Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1	Day 1 PK peak concentration will be summarized by the mean and the standard deviation.
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Tmax	Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1	Day 1 PK time to peak concentration will be summarized by the mean and the standard deviation.
Overall Survival (OS)	Up to 1 year	The 1-year Overall Survival will be estimated using Kaplan-Meier methodology.
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: AUC	Prior to dose, 2, 4, 8 and 20-28 hours after dose on day 1	Day 1 PK area under the curve will be summarized by the mean and the standard deviation.
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Accumulation	Cycle 1, Day 1 (20-28 hours after dose) and Cycle 1, Day 22	PK accumulation will be summarized by the mean and the standard deviation.
Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Half-life	Cycle 1, Day 1 (20-28 hours after dose) and Cycle 1, Day 22	PK half-life will be summarized by the mean and the standard deviation.
Time to Progression (TTP)	Up to 1 year	Percent of patients not yet progressed at 1 year as estimated by the Kaplan-Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as a \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Clinical progression was also counted as an event for this analysis.
Progression Free Survival (PFS)	Up to 1 year	The 1-year Progression Free Survival will be estimated using Kaplan-Meier methodology. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as a \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Percentage of Participants With Adverse Events	Up to 5 years (duration of protocol therapy plus 30 days after last dose of therapy)	Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy

Trial Locations

Locations (142): UCSF Medical Center-Mission Bay
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San Francisco, California, United States
Henry Ford Health Saint John Hospital
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Detroit, Michigan, United States
Huron Medical Center PC
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Port Huron, Michigan, United States
Corewell Health Children's
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Royal Oak, Michigan, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
Providence Alaska Medical Center
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Anchorage, Alaska, 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
Kaiser Permanente-Bellflower
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Bellflower, California, United States
Kaiser Permanente Downey Medical Center
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Downey, California, United States
Kaiser Permanente-Fontana
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Fontana, California, United States
Loma Linda University Medical Center
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Loma Linda, 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
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
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
Kaiser Permanente-San Diego Mission
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San Diego, California, United States
Rady Children's Hospital - San Diego
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San Diego, California, United States
Children's Hospital Colorado
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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
Yale University
🇺🇸
New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Kaiser Permanente-Capitol Hill Medical Center
🇺🇸
Washington, District of Columbia, United States
MedStar Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Golisano Children's Hospital of Southwest Florida
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Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville
🇺🇸
Gainesville, Florida, United States
Nemours Children's Clinic-Jacksonville
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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
Arnold Palmer Hospital for Children
🇺🇸
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
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Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
🇺🇸
Atlanta, 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
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Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
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Boise, Idaho, United States
Lurie Children's Hospital-Chicago
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Chicago, Illinois, United States
University of Illinois
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Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, United States
Carle at The Riverfront
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Danville, Illinois, United States
Carle Physician Group-Effingham
🇺🇸
Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸
Mattoon, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
The Carle Foundation Hospital
🇺🇸
Urbana, Illinois, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸
Indianapolis, Indiana, United States
Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
Iowa Methodist 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
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
Norton Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Children's Hospital New Orleans
🇺🇸
New Orleans, Louisiana, United States
Eastern Maine Medical Center
🇺🇸
Bangor, Maine, United States
Lafayette Family Cancer Center-EMMC
🇺🇸
Brewer, Maine, United States
Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, United States
National Institutes of Health Clinical Center
🇺🇸
Bethesda, Maryland, United States
Massachusetts General Hospital Cancer Center
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Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
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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
Siteman Cancer Center at West County Hospital
🇺🇸
Creve Coeur, Missouri, United States
Children's Mercy Hospitals and Clinics
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Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center
🇺🇸
Saint Louis, Missouri, United States
Barnes-Jewish Hospital
🇺🇸
Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸
Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
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Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸
Saint Peters, Missouri, United States
Children's Hospital and Medical Center of Omaha
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Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Comprehensive Cancer Centers of Nevada-Horizon Ridge
🇺🇸
Henderson, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸
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
Hope Cancer Care of Nevada-Pahrump
🇺🇸
Pahrump, 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
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, 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
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸
Clinton, North Carolina, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Southeastern Medical Oncology Center-Goldsboro
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Goldsboro, North Carolina, United States
Wayne Memorial Hospital
🇺🇸
Goldsboro, North Carolina, United States
East Carolina University
🇺🇸
Greenville, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
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Jacksonville, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
ProMedica Flower Hospital
🇺🇸
Sylvania, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Saint Francis Hospital
🇺🇸
Greenville, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
Saint Francis Cancer Center
🇺🇸
Greenville, South Carolina, 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
Medical City Dallas 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
Texas Tech University Health Sciences Center-El Paso
🇺🇸
El Paso, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
Children's Hospital of San Antonio
🇺🇸
San Antonio, Texas, United States
University of Vermont and State Agricultural College
🇺🇸
Burlington, Vermont, United States
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Gundersen Lutheran Medical Center
🇺🇸
La Crosse, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸
Madison, Wisconsin, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States