Vinorelbine Tartrate and Cyclophosphamide in Combination With Bevacizumab or Temsirolimus in Treating Patients With Recurrent or Refractory Rhabdomyosarcoma

Phase 2

Completed

Conditions: Childhood Alveolar Rhabdomyosarcoma
Childhood Pleomorphic Rhabdomyosarcoma
Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features
Recurrent Childhood Rhabdomyosarcoma
Adult Rhabdomyosarcoma
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Adult Soft Tissue Sarcoma

Interventions: Biological: Bevacizumab
Other: Laboratory Biomarker Analysis
Drug: Cyclophosphamide
Drug: Temsirolimus
Drug: Vinorelbine Tartrate

Registration Number: NCT01222715

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase II trial studies how well vinorelbine tartrate and cyclophosphamide work in combination with bevacizumab or temsirolimus in treating patients with recurrent or refractory rhabdomyosarcoma. Drugs used in chemotherapy, such as vinorelbine tartrate and cyclophosphamide, 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 bevacizumab, 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. Bevacizumab may also stop the growth of rhabdomyosarcoma by blocking blood flow to the tumor. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective when given together with bevacizumab or temsirolimus in treating rhabdomyosarcoma.

Detailed Description: PRIMARY OBJECTIVES:

l. To determine the feasibility of administering bevacizumab in combination with intravenous vinorelbine (vinorelbine tartrate) and cyclophosphamide (VC) in patients with recurrent rhabdomyosarcoma (RMS).

II. To determine the feasibility of administering temsirolimus in combination with VC in patients with recurrent RMS.

III. To estimate the event-free survival (EFS) of patients with recurrent/refractory RMS treated with bevacizumab and VC and compare with the EFS of those treated with temsirolimus and VC.

SECONDARY OBJECTIVES:

I. To estimate the initial (2 cycle) response rate of patients with recurrent/refractory RMS treated with bevacizumab and VC and compare with the response rate of those treated with temsirolimus and VC, and to also compare the best response rate on each regimen of protocol therapy.

II. To evaluate surrogate biological markers in patients with recurrent RMS and to estimate differences in these markers following treatment with bevacizumab and temsirolimus.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive vinorelbine tartrate intravenously (IV) over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.

ARM II: Patients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.

In both arms, treatment repeats every 21 days for 12 courses in the absence of disease progression or unacceptable toxicity.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 87

Inclusion Criteria

Diagnosis
- Patients with first relapse or progression of rhabdomyosarcoma are eligible
- Patients with primary refractory disease are eligible
  - Primary refractory disease is defined as first progression after receiving at least one course of cyclophosphamide or ifosfamide containing chemotherapy without prior demonstration of a radiographic response to chemotherapy (progression on irinotecan-containing chemotherapy without cyclophosphamide or ifosfamide containing chemotherapy will not be considered a first progression)
- Note: Patients without measurable or evaluable disease are eligible
Patients must have had a previous histological verification of rhabdomyosarcoma at original diagnosis
Patients must have a Karnofsky or Lansky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
Patients must have a life expectancy of >= 8 weeks
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Myelosuppressive chemotherapy: Must not have received within 3 weeks prior to entry onto this study (4 weeks if prior nitrosourea)
Biologic (anti-neoplastic agent):
- Patients may have received prior therapy with oral tyrosine kinase inhibitors or other similar agents; at least 7 days must have elapsed since the completion of therapy with a biologic agent and all toxicities must have resolved to < grade 2 prior to enrollment
- 3 half-lives (or 6 weeks) must have elapsed since previous monoclonal antibody therapy prior to enrollment on this study
Myeloid growth factor: Must not have received within 1 week prior to entry onto this study
Radiation therapy (RT): At least 4 weeks must have elapsed between RT and study entry; previously radiated lesions cannot be used to assess response unless those sites are the sites of disease progression
Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed; for allogeneic SCT, >= 6 months must have elapsed and no evidence of active graft vs. host disease
Patients must have recovered from any surgical procedure before enrolling on this study
- Minor surgical procedures (e.g., biopsies involving core or fine-needle aspiration procedures, infusaport or Broviac line placement, paracentesis, or thoracocentesis) need to have fully healed and occurred > 7 days prior to enrollment
- Patients who have had a major surgical procedure (such as laparotomy, thoracotomy, open biopsy, or resection of tumor) can only be enrolled on study > 28 days from such procedure
Peripheral absolute neutrophil count (ANC) >= 750/μL
Platelet count >= 75,000/μL (transfusion independent, defined as without transfusion for >= 1 week prior to enrollment)
Hemoglobin >= 8.0 g/dL (may receive packed red blood cells [PRBC] transfusions)
Bone marrow disease involvement of tumor is allowed, however, peripheral blood count criteria must still be met
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:
- =< 0.4 mg/dL (for patients aged 1 month to < 6 months)
- =< 0.5 mg/dL (for patients aged 6 months to < 1 year)
- =< 0.6 mg/dL (for patients aged 1 to < 2 years)
- =< 0.8 mg/dL (for patients aged 2 to < 6 years)
- =< 1 mg/dL (for patients aged 6 to < 10 years)
- =< 1.2 mg/dL (for patients aged 10 to < 13 years)
- =< 1.4 mg/dL (for female patients aged >= 13 years)
- =< 1.5 mg/dL (for male patients aged 13 to < 16 years)
- =< 1.7 mg/dL (for male patients aged >= 16 years)
Urine protein level:
- Patients aged =< 17 years: Urine protein to creatinine (UPC) ratio should be calculated; UPC ratio must be =< 1 for patient to be eligible
- Patients aged > 17 years: Urine protein should be screened by urine analysis; if protein is 2+ or higher, 24-hour urine protein must be obtained and the level must be < 1,000 mg for patient enrollment
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by radionuclide angiogram

Exclusion Criteria

Patients with botryoid histology, any stage or group, are ineligible
Patients with embryonal histology, stage I or clinical group 1 at initial disease presentation, who present with local or regional recurrence, are ineligible
Patients who previously received craniospinal irradiation are ineligible
Patients who previously received vinorelbine, bevacizumab, temsirolimus, or any other direct vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR-) or mammalian target of rapamycin (mTOR-) targeting agents are ineligible
Patients with known central nervous system (CNS) disease (excluding intracranial/intraspinal extension secondary to local progression of a parameningeal or paraspinal primary), except for those with treated brain metastasis, are ineligible
- Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]); stable dose of anticonvulsants are allowed; treatment for brain metastases may include whole-brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent), or a combination as deemed appropriate by the treating physician
- Patients with CNS metastases treated within 3 months prior to enrollment by neurosurgical resection or brain biopsy are ineligible
Patients who receive radiation or chemotherapy (inclusive of palliative intent) for first disease progression or relapse of rhabdomyosarcoma prior to enrollment are ineligible
Female patients who are pregnant are ineligible
Lactating females are not eligible unless they have agreed to discontinue breastfeeding
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
Patients with a documented chronic non-healing wound, ulcer, or significant trauma injury (those with bone fractures, including pathological fractures, or requiring surgical intervention) within 28 days prior to beginning therapy are ineligible
Patients with evidence of intratumoral hemorrhage, gastrointestinal bleeding, or on anticoagulation for thrombosis or history of thrombosis are ineligible
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 that is not controlled by one antihypertensive medication
- Patients aged > 17 years: systolic blood pressure >= 160 mm Hg and/or diastolic blood pressure >= 90 mm Hg that is not controlled by one antihypertensive medication
Patients currently taking anticoagulants or antiplatelet agents with the exception of aspirin (=< 81 mg/day) are ineligible
Patients with history of central venous catheter (CVC)-associated thrombosis requiring systemic anticoagulation are ineligible; Note: Patients with history of sluggish flow from CVC or CVC-associated thrombosis treated with tissue plasminogen activator (TPA) only are not excluded
Patients with clinically significant cardiovascular disease are excluded:
- History of cerebrovascular accident (CVA) within the prior 6 months
- Myocardial infarction or unstable angina within the prior 6 months
- New York Heart Association grade 2 or greater congestive heart failure
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
- Clinically significant peripheral vascular disease
Patients diagnosed with rhabdomyosarcoma as a second malignant neoplasm are not eligible
Patients with history of any second malignant neoplasm who have received chemotherapy or radiation for the treatment of that malignancy are not eligible

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (vinorelbine tartrate, cyclophosphamide, bevacizumab)	Vinorelbine Tartrate	Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.
Arm II (vinorelbine tartrate, cyclophosphamide, temsirolimus)	Vinorelbine Tartrate	Patients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.
Arm II (vinorelbine tartrate, cyclophosphamide, temsirolimus)	Laboratory Biomarker Analysis	Patients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.
Arm I (vinorelbine tartrate, cyclophosphamide, bevacizumab)	Bevacizumab	Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.
Arm I (vinorelbine tartrate, cyclophosphamide, bevacizumab)	Laboratory Biomarker Analysis	Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.
Arm I (vinorelbine tartrate, cyclophosphamide, bevacizumab)	Cyclophosphamide	Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.
Arm II (vinorelbine tartrate, cyclophosphamide, temsirolimus)	Cyclophosphamide	Patients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.
Arm II (vinorelbine tartrate, cyclophosphamide, temsirolimus)	Temsirolimus	Patients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.

Primary Outcome Measures

Name	Time	Method
Event Free Survival Probability	1 year	Probability of no relapse, secondary malignancy, or death after 1 year in the study.
Rate of Dose-Limiting Toxicities	From the date of randomization until a maximum of 12 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities.	The following events will be considered dose-limiting toxicities (DLTs): Toxicity causing delays \> 14 days in delivery of a 21-day cycle of therapy; Grade ≥ 3 mucositis \> 3 days duration; Grade ≥ 3 thromboembolic events; Grade ≥ 3 bleeding events; Grade ≥ 3 pulmonary events; Grade ≥ 3 hypertension; Grade 3 hyperglycemia (uncontrolled); Grade ≥ 4 hyperglycemia; Grade ≥ 4 hyperlipidemia (including cholesterol and triglycerides) that does not return to ≤ Grade 2 levels with appropriate medical management within 35 days; Grade ≥ 2 perforation including fistula or leak (gastrointestinal or any other organ); Grade ≥ 3 proteinuria; Grade ≥ 3 cardiac toxicity; Grade ≥ 3 intra-abdominal abscess/infection; Grade ≥ 3 wound complication (wound infection or dehiscence); Grade ≥ 1 Reversible Posterior Leukoencephalopathy Syndrome (RPLS); Grade ≥ 1 Microangiopathy, or Hemolytic-uremic syndrome (HUS) or Thrombotic thrombocytopenic Purpura (TTP).

Secondary Outcome Measures

Name	Time	Method
Response Rate (CR + PR)	From the date of randomization until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities.	Complete or partial anatomical response rate. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

Trial Locations

Locations (184): New York Medical College
🇺🇸
Valhalla, New York, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
University of Illinois
🇺🇸
Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
Southern California Permanente Medical Group
🇺🇸
Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸
Long Beach, California, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Memorial University Medical Center
🇺🇸
Savannah, Georgia, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸
Boise, Idaho, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Dana-Farber/Harvard Cancer Center
🇺🇸
Boston, Massachusetts, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
Michigan State University Clinical Center
🇺🇸
East Lansing, Michigan, United States
Kalamazoo Center for Medical Studies
🇺🇸
Kalamazoo, Michigan, United States
University of Missouri - Ellis Fischel
🇺🇸
Columbia, Missouri, United States
Saint Peter's University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸
Paterson, New Jersey, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸
New York, New York, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Columbia University/Herbert Irving Cancer Center
🇺🇸
New York, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Sanford Medical Center-Fargo
🇺🇸
Fargo, North Dakota, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Mercy Children's Hospital
🇺🇸
Toledo, Ohio, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸
Tulsa, Oklahoma, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
St. Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
Texas Tech University Health Science Center-Amarillo
🇺🇸
Amarillo, Texas, United States
Medical City Dallas Hospital
🇺🇸
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Brooke Army Medical Center
🇺🇸
Fort Sam Houston, 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
University of Vermont College of Medicine
🇺🇸
Burlington, Vermont, United States
Scott and White Memorial Hospital
🇺🇸
Temple, Texas, United States
University of Virginia Cancer Center
🇺🇸
Charlottesville, Virginia, United States
Childrens Hospital-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
Mary Bridge Children's Hospital and Health Center
🇺🇸
Tacoma, Washington, United States
West Virginia University Charleston
🇺🇸
Charleston, West Virginia, United States
The Children's Hospital at Westmead
🇦🇺
Westmead, New South Wales, Australia
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Sydney Children's Hospital
🇦🇺
Randwick, New South Wales, Australia
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Allan Blair Cancer Centre
🇨🇦
Regina, Saskatchewan, Canada
Saskatoon Cancer Centre
🇨🇦
Saskatoon, Saskatchewan, Canada
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Saint Vincent Hospital and Health Care Center
🇺🇸
Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Saint Mary's Hospital
🇺🇸
West Palm Beach, Florida, 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
Floating Hospital for Children at Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Nevada Cancer Research Foundation CCOP
🇺🇸
Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
Hackensack University Medical Center
🇺🇸
Hackensack, 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
Palmetto Health Richland
🇺🇸
Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, 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
Alberta Children's Hospital
🇨🇦
Calgary, Alberta, Canada
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Janeway Child Health Centre
🇨🇦
Saint John's, Newfoundland and Labrador, Canada
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦
Quebec, Canada
Children's Hospital
🇨🇦
London, Ontario, Canada
Starship Children's Hospital
🇳🇿
Grafton, Auckland, New Zealand
Christchurch Hospital
🇳🇿
Christchurch, New Zealand
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, 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
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Winthrop University Hospital
🇺🇸
Mineola, New York, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸
New Hyde Park, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Stony Brook University Medical Center
🇺🇸
Stony Brook, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Mission Hospital-Memorial Campus
🇺🇸
Asheville, North Carolina, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
Penn State Hershey Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Inova Fairfax Hospital
🇺🇸
Falls Church, Virginia, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸
Oakland, California, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Saint Barnabas Medical Center
🇺🇸
Livingston, New Jersey, United States
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
University of Minnesota/Masonic Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Phoenix Childrens Hospital
🇺🇸
Phoenix, Arizona, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸
Denver, Colorado, United States
Legacy Emanuel Children's Hospital
🇺🇸
Portland, Oregon, United States
Legacy Emanuel Hospital and Health Center
🇺🇸
Portland, Oregon, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Midwest Children's Cancer Center
🇺🇸
Milwaukee, Wisconsin, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸
Tampa, Florida, United States
Walter Reed National Military Medical Center
🇺🇸
Bethesda, Maryland, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸
Orlando, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸
Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
The Childrens Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Children's Hospital New Orleans
🇺🇸
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
Dell Children's Medical Center of Central Texas
🇺🇸
Austin, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Greenville Cancer Treatment Center
🇺🇸
Greenville, South Carolina, United States
Chedoke Hospital at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
The Toledo Hospital/Toledo Children's Hospital
🇺🇸
Toledo, Ohio, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States