Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma
- Conditions
- Localized OsteosarcomaMetastatic Osteosarcoma
- Interventions
- Other: Quality-of-Life AssessmentBiological: Peginterferon Alfa-2bOther: Questionnaire AdministrationProcedure: Therapeutic Conventional Surgery
- Registration Number
- NCT00134030
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This randomized phase III trial is studying combination chemotherapy followed by surgery and two different combination chemotherapy regimens with or without PEG-interferon alfa-2b to compare how well they work in treating patients with osteosarcoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Biological therapies, such as PEG-interferon alfa-2b, may interfere with the growth of tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so it can be removed. Giving combination chemotherapy together with PEG-interferon alfa-2b after surgery may kill any remaining tumor cells. It is not yet known whether giving combination therapy together with PEG-interferon alfa-2b is more effective than two different combination chemotherapy regimens alone after surgery in treating osteosarcoma.
- Detailed Description
PRIMARY OBJECTIVES:
I. Compare whether adjuvant maintenance therapy comprising doxorubicin, cisplatin, and high-dose methotrexate (MAP) alone vs MAP combined with ifosfamide and etoposide improves event-free survival of patients with resectable high-grade osteosarcoma who achieve a poor histological response (HR) to neoadjuvant induction therapy comprising MAP.
II. Compare whether adjuvant maintenance therapy comprising MAP alone vs MAP and PEG-interferon alfa-2b improves event-free survival of patients with resectable high-grade osteosarcoma who achieve a good HR to neoadjuvant induction therapy comprising MAP.
SECONDARY OBJECTIVES:
I. Compare overall survival of patients treated with these regimens. II. Compare short- and long-term toxicity of these regimens in these patients. III. Compare quality of life of patients treated with these regimens. IV. Compare event-free survival and overall survival of patients with localized osteosarcoma treated with these regimens.
V. Correlate biological or clinical changes with histological response and outcomes in patients treated with these regimens.
VI. Determine outcomes of patients treated with these regimens.
OUTLINE: This is a randomized, controlled, multicenter study.
INDUCTION THERAPY: (MAP; weeks 1-10) Patients receive doxorubicin IV continuously over 48 hours on days 1-2 and cisplatin IV over 4 hours on days 1 and 2 in weeks 1 and 6. Patients also receive high-dose methotrexate (MTX)\* IV over 4 hours on day 1 in weeks 4, 5, 9, and 10. Patients then proceed to surgery.
NOTE: \*Patients must receive \>= 2 but =\< 6 doses of high-dose MTX.
SURGERY: Patients undergo amputation or limb salvage surgery in week 11. Tumor tissue is evaluated for histological response to induction therapy. Patients whose tumor is not amenable to macroscopically complete surgical resection undergo radiotherapy and/or other investigational therapy off study. Patients who undergo macroscopically complete surgical resection of the primary tumor or metastases AND who have no disease progression or unacceptable toxicity proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients are assigned to 1 of 2 groups according to histological response (good \[\< 10% viable tumor\] vs poor \[≥ 10% viable tumor\]). Patients in each group are stratified according to site of primary tumor and presence of metastases.
GROUP 1: (good histological response) Patient are randomized to 1 of 2 treatment arms within 35 days after surgery.
ARM I: (MAP; weeks 12-29) Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29.
ARM II: (MAPifn; weeks 12-104) Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104.
GROUP 2: (poor histological response) Patients are randomized to 1 of 2 treatment arms within 35 days after surgery.
ARM I: (MAP; weeks 12-29) Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I.
ARM II: (MAPIE; weeks 12-40) Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32.
In both groups, treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed periodically.
After completion of study treatment, patients are followed every 1½-3 months for 2 years, every 2-4 months for 2 years, every 6 months for 6 years, and then every 6-12 months thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1334
-
Histologically confirmed high-grade osteosarcoma, including second malignancies
-
Localized or metastatic disease
-
The primary tumor must be located in the limbs or axial skeleton, including any of the following sites*:
- Long bone of upper limb
- Short bone of upper limb
- Long bone of lower limb
- Short bone of lower limb
- Vertebral column
- Ribs, sternum, clavicle, or scapula
- Pelvic bones, sacrum, or coccyx
-
-
Tumor (primary, metastatic, or both) resectable OR is expected to become resectable after neoadjuvant induction chemotherapy
-
Suitable for neoadjuvant chemotherapy
-
Performance status - Lansky 50-100% (for patients under 16 years of age)
-
Performance status - Karnofsky 50-100%*
-
Performance status - WHO or ECOG 0-2*
-
Platelet count ≥ 100,000/mm³
-
Neutrophil count ≥ 1,500/mm³
-
WBC ≥ 3,000/mm³
-
Bilirubin ≤ 1.5 times upper limit of normal
-
Creatinine clearance ≥ 70 mL/min
-
Creatinine based on age as follows:
- No greater than 1.0 mg/dL (for patients 5 to 10 years of age)
- No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
- No greater than 1.5 mg/dL (for patients over 15 years of age)
-
Ejection fraction ≥ 50% by radionuclide angiogram
-
Shortening fraction ≥ 28% by echocardiogram
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
No known HIV positivity
-
No prior chemotherapy for any disease
-
Prior radiotherapy for another malignancy allowed
-
No prior treatment for osteosarcoma
-
No patients with any of the following:
- Craniofacial osteosarcoma
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Maintenance therapy group 1 arm II Therapeutic Conventional Surgery Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Maintenance therapy group 1 arm I Questionnaire Administration Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Maintenance therapy group 1 arm I Quality-of-Life Assessment Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Maintenance therapy group 1 arm I Therapeutic Conventional Surgery Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Maintenance therapy group 1 arm II Quality-of-Life Assessment Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Maintenance therapy group 2 arm II Quality-of-Life Assessment Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Maintenance therapy group 2 arm II Questionnaire Administration Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Maintenance therapy group 1 arm II Peginterferon Alfa-2b Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Maintenance therapy group 1 arm II Questionnaire Administration Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Maintenance therapy group 2 arm I Questionnaire Administration Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Maintenance therapy group 2 arm I Therapeutic Conventional Surgery Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Maintenance therapy group 2 arm I Quality-of-Life Assessment Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Maintenance therapy group 2 arm II Therapeutic Conventional Surgery Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Maintenance therapy group 1 arm I Doxorubicin Hydrochloride Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Maintenance therapy group 1 arm I Cisplatin Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Maintenance therapy group 1 arm I Methotrexate Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Maintenance therapy group 1 arm II Cisplatin Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Maintenance therapy group 1 arm II Methotrexate Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Maintenance therapy group 1 arm II Doxorubicin Hydrochloride Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Maintenance therapy group 2 arm I Methotrexate Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Maintenance therapy group 2 arm I Cisplatin Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Maintenance therapy group 2 arm I Doxorubicin Hydrochloride Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Maintenance therapy group 2 arm II Cisplatin Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Maintenance therapy group 2 arm II Etoposide Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Maintenance therapy group 2 arm II Doxorubicin Hydrochloride Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Maintenance therapy group 2 arm II Methotrexate Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Maintenance therapy group 2 arm II Ifosfamide Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32.
- Primary Outcome Measures
Name Time Method Event-free Survival (EFS) From date of randomization to date of the event. EFS is defined as time from randomisation to the first of: death, detection of local recurrence or metastasis, progression of metastatic disease, or detection of a secondary malignancy.
EFS will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Follow up per participant will be assessed for up to 10 years. The 3 year EFS is provided as a summary.
- Secondary Outcome Measures
Name Time Method Percentage of Patients With Overall Survival From date of randomization to date of death. Overall survival is time from randomization until death from any cause.
Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Participants will be assessed for up to 10 years. 5 year overall survival is provided as a summary.Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Adverse events are assessed for up to 10 years per participant. Percentages of patients experiencing grade 3 and 4 adverse events. These will be compared using chi-square tests or Fisher's exact tests where appropriate.
Trial Locations
- Locations (218)
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Beaumont Children's Hospital-Royal Oak
🇺🇸Royal Oak, Michigan, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, 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
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
Brooklyn Hospital Center
🇺🇸Brooklyn, New York, United States
Mission Hospital
🇺🇸Asheville, North Carolina, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
John Hunter Children's Hospital
🇦🇺Newcastle, New South Wales, Australia
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, 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
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Care Center
🇺🇸Indianapolis, Indiana, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
University of Connecticut
🇺🇸Farmington, Connecticut, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
UMass Memorial Medical Center - University Campus
🇺🇸Worcester, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
William Beaumont Hospital-Royal Oak
🇺🇸Royal Oak, Michigan, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
West Virginia University Charleston Division
🇺🇸Charleston, West Virginia, United States
Cabell-Huntington Hospital
🇺🇸Huntington, West Virginia, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Royal Children's Hospital-Brisbane
🇦🇺Herston, Queensland, Australia
Queensland Children's Hospital
🇦🇺South Brisbane, Queensland, Australia
Women's and Children's Hospital-Adelaide
🇦🇺North Adelaide, South Australia, Australia
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Janeway Child Health Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
Victoria Hospital
🇨🇦London, Ontario, Canada
Children's Hospital
🇨🇦London, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, 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
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Starship Children's Hospital
🇳🇿Grafton, Auckland, New Zealand
Wellington Children's Hospital
🇳🇿Wellington, New Zealand
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
Swiss Pediatric Oncology Group - Geneva
🇨🇭Geneva, Switzerland
Swiss Pediatric Oncology Group - Lausanne
🇨🇭Lausanne, Switzerland
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Mattel Children's Hospital UCLA
🇺🇸Los Angeles, California, United States
UCLA / Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, 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
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Harbor-University of California at Los Angeles Medical Center
🇺🇸Torrance, California, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸Toledo, Ohio, United States
Mercy Children's Hospital
🇺🇸Toledo, Ohio, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Tech University Health Sciences Center-Amarillo
🇺🇸Amarillo, Texas, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Carilion Children's
🇺🇸Roanoke, Virginia, 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
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
University of Rochester
🇺🇸Rochester, New York, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Ascension Saint John Hospital
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, 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
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Swiss Pediatric Oncology Group - Bern
🇨🇭Bern, Switzerland
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Mayo Clinic in Rochester
🇺🇸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
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, 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
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
Yale University
🇺🇸New Haven, Connecticut, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Children's Mercy Hospitals and Clinics
🇺🇸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 Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Tripler Army Medical Center
🇺🇸Honolulu, Hawaii, 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
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States