Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma
Metastatic Ewing Sarcoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Neoplasm in the Bone Marrow
About this trial
This is an interventional treatment trial for Metastatic Ewing Sarcoma
Eligibility Criteria
Inclusion Criteria:
- Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site
For the purpose of this study metastatic disease is defined as one or more of the following:
- Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor; skip lesions in the same bone as the primary tumor do not constitute metastatic disease; skip lesions in an adjacent bone are considered bone metastases; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed
- Contralateral pleural effusion and/or contralateral pleural nodules
- Distant lymph node involvement
Patients with pulmonary nodules are considered to have metastatic disease if the patient has:
- Solitary nodule >= 0.5 cm or multiple nodules of >= 0.3 cm unless lesion is biopsied and negative for tumor
- Patients with solitary nodule < 0.5 cm or multiple nodules < 0.3 cm are not considered to have lung metastasis unless biopsy documents tumor
Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma based on hematoxylin and eosin (H&E) stains; in the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse-transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
- This study requires bilateral bone marrow biopsies at study entry; the suggested approach for patients with large pelvic tumors in which a posterior iliac crest bone marrow biopsy would track through the tumor is to instead undergo 2 marrow biopsies on the contralateral side (either 2 posterior biopsies or one posterior and one anterior biopsy)
- Bone metastasis: This study utilizes whole body FDG-PET scans to screen patients for bone metastases; areas suspicious for bone metastasis based on FDG-PET scans require confirmatory anatomic imaging with either MRI or computed tomography (CT) (whole body FDG-PET/CT or FDG-PET/magnetic resonance [MR] scan acceptable); whole body technetium bone scans may be performed at the discretion of the investigator and are not required; for patients without other sites of metastatic disease whose sole metastatic site to qualify for study entry is a single area suspicious for bone metastasis identified by FDG-PET, confirmatory biopsy or anatomic imaging evidence of an associated soft tissue mass at that site is required for study entry
- Patients must have adequate tumor tissue to meet the minimum requirement for submission
- Enrolling institutions are reminded that submission of pre-treatment serum, tumor tissue and whole blood is required
- Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery
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 (performed within 7 days prior to enrollment):
- Age < 6 months: Maximum serum creatinine (mg/dL): 0.4 for males and females
- Age 6 months to < 1 year: Maximum serum creatinine (mg/dL): 0.5 for males and females
- Age 1 to < 2 years: Maximum serum creatinine (mg/dL): 0.6 for males and females
- Age 2 to < 6 years: Maximum serum creatinine (mg/dL): 0.8 for males and females
- Age 6 to < 10 years: Maximum serum creatinine (mg/dL): 1 for males and females
- Age 10 to < 13 years: Maximum serum creatinine (mg/dL): 1.2 for males and females
- Age 13 to < 16 years: Maximum serum creatinine (mg/dL): 1.5 for males and 1.4 for females
- Age >= 16 years: Maximum serum creatinine (mg/dL): 1.7 for males and 1.4 for females
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment), and
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (except for patients with liver metastasis who may enroll if ALT < 5 times ULN for age)
- Shortening fraction of >= 27% or
- Ejection fraction of >= 50%
- Patients must have a normal blood sugar level for age to participate; if an initial random draw (ie. non-fasting) blood glucose value is out of range, it is acceptable to repeat this test as a fasting draw
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
- Patients with regional node involvement as their only site of disease beyond the primary tumor will not be eligible
- Patients whose primary tumors arise in the intra-dural soft tissue (e.g. brain and spinal cord) are not eligible
- Patients who have received prior chemotherapy or radiation therapy are not eligible
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained; lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of protocol therapy; sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of protocol therapy
- Patients with known pre-existing diabetes mellitus will be excluded from study
- Patients receiving chronic pharmacologic doses of corticosteroids are not eligible; for the purposes of eligibility, chronic exposure is defined as anticipated exposure of > 3 weeks, including the sum of both pre-enrollment and anticipated post-enrollment dosing; patients on acute corticosteroid therapy (=< 3 weeks of total planned exposure) must still meet the normal blood glucose requirement; patients receiving chronic inhaled corticosteroids or chronic physiologic replacement doses of corticosteroids are eligible
Sites / Locations
- Children's Hospital of Alabama
- USA Health Strada Patient Care Center
- Providence Alaska Medical Center
- Banner Children's at Desert
- Phoenix Childrens Hospital
- Banner University Medical Center - Tucson
- Yuma Regional Medical Center
- CHI Saint Vincent Cancer Center Hot Springs
- Arkansas Children's Hospital
- Kaiser Permanente Downey Medical Center
- City of Hope Comprehensive Cancer Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital Stanford University
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Rady Children's Hospital - San Diego
- UCSF Medical Center-Parnassus
- UCSF Medical Center-Mission Bay
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital Colorado
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Porter Adventist Hospital
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
- Mercy Medical Center
- Southwest Oncology PC
- Mountain Blue Cancer Care Center
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony Hospital
- Littleton Adventist Hospital
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- Rocky Mountain Cancer Centers - Pueblo
- Rocky Mountain Cancer Centers-Thornton
- Connecticut Children's Medical Center
- Yale University
- Alfred I duPont Hospital for Children
- MedStar Georgetown University Hospital
- Children's National Medical Center
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Nemours Children's Clinic-Jacksonville
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Hospital
- Nemours Children's Clinic - Pensacola
- Johns Hopkins All Children's Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Augusta University Medical Center
- Memorial Health University Medical Center
- Straub Clinic and Hospital
- Kaiser Permanente Moanalua Medical Center
- Kapiolani Medical Center for Women and Children
- Saint Luke's Cancer Institute - Boise
- Rush - Copley Medical Center
- Lurie Children's Hospital-Chicago
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Carle at The Riverfront
- Carle Physician Group-Effingham
- Carle Physician Group-Mattoon/Charleston
- Loyola University Medical Center
- Good Samaritan Regional Health Center
- Advocate Children's Hospital-Oak Lawn
- Advocate Children's Hospital-Park Ridge
- Saint Jude Midwest Affiliate
- Saint John's Hospital
- Southern Illinois University School of Medicine
- Memorial Medical Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Rush-Copley Healthcare Center
- Deaconess Clinic Downtown
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- Franciscan Saint Anthony Health-Michigan City
- Woodland Cancer Care Center
- Chancellor Center for Oncology
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Blank Children's Hospital
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- University of Iowa/Holden Comprehensive Cancer Center
- Mercy Medical Center-West Lakes
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- University of Kentucky/Markey Cancer Center
- Saint Joseph London
- Jewish Hospital
- Norton Children's Hospital
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Children's Hospital New Orleans
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Maine Children's Cancer Program
- University of Maryland/Greenebaum Cancer Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- Baystate Medical Center
- UMass Memorial Medical Center - University Campus
- C S Mott Children's Hospital
- University of Michigan Comprehensive Cancer Center
- Bronson Battle Creek
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Trinity Health Muskegon Hospital
- Lakeland Hospital Niles
- Huron Medical Center PC
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- Beaumont Children's Hospital-Royal Oak
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Munson Medical Center
- Essentia Health Cancer Center
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Central Care Cancer Center - Bolivar
- Cox Cancer Center Branson
- Columbia Regional
- Freeman Health System
- Mercy Hospital Joplin
- Children's Mercy Hospitals and Clinics
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Cardinal Glennon Children's Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Nebraska Medicine-Bellevue
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Children's Hospital and Medical Center of Omaha
- Nebraska Medicine-Village Pointe
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- University of Nebraska Medical Center
- Midlands Community Hospital
- Carson Tahoe Regional Medical Center
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
- University Medical Center of Southern Nevada
- Sunrise Hospital and Medical Center
- Ann M Wierman MD LTD
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Hope Cancer Care of Nevada-Pahrump
- Renown Regional Medical Center
- Saint Mary's Regional Medical Center
- Radiation Oncology Associates
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Hackensack University Medical Center
- Morristown Medical Center
- Saint Peter's University Hospital
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Newark Beth Israel Medical Center
- Saint Joseph's Regional Medical Center
- Albany Medical Center
- Montefiore Medical Center-Einstein Campus
- Montefiore Medical Center-Weiler Hospital
- Children's Hospital at Montefiore
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- Glens Falls Hospital
- NYU Winthrop Hospital
- The Steven and Alexandra Cohen Children's Medical Center of New York
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- New York Medical College
- Mission Hospital
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Duke University Medical Center
- Wake Forest University Health Sciences
- Sanford Broadway Medical Center
- Children's Hospital Medical Center of Akron
- Good Samaritan Hospital - Cincinnati
- Cincinnati Children's Hospital Medical Center
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Rainbow Babies and Childrens Hospital
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Oklahoma Health Sciences Center
- Mercy Hospital Oklahoma City
- Legacy Emanuel Children's Hospital
- Oregon Health and Science University
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Penn State Children's Hospital
- Drexel University School of Medicine
- Children's Hospital of Philadelphia
- Saint Christopher's Hospital for Children
- Children's Hospital of Pittsburgh of UPMC
- Rhode Island Hospital
- Medical University of South Carolina
- Prisma Health Richland Hospital
- Saint Francis Hospital
- BI-LO Charities Children's Cancer Center
- Saint Francis Cancer Center
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- East Tennessee Childrens Hospital
- Saint Jude Children's Research Hospital
- The Children's Hospital at TriStar Centennial
- Vanderbilt University/Ingram Cancer Center
- Memorial GYN Plus
- Dell Children's Medical Center of Central Texas
- Saint Joseph Regional Cancer Center
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- El Paso Children's Hospital
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- M D Anderson Cancer Center
- Covenant Children's Hospital
- UMC Cancer Center / UMC Health System
- Texas Tech University Health Sciences Center-Lubbock
- Children's Hospital of San Antonio
- Methodist Children's Hospital of South Texas
- University of Texas Health Science Center at San Antonio
- Scott and White Memorial Hospital
- Primary Children's Hospital
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- University of Vermont and State Agricultural College
- Inova Fairfax Hospital
- Children's Hospital of The King's Daughters
- Naval Medical Center - Portsmouth
- Virginia Commonwealth University/Massey Cancer Center
- Carilion Children's
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Saint Elizabeth Hospital
- Saint Francis Hospital
- Saint Clare Hospital
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Franciscan Research Center-Northwest Medical Plaza
- Mary Bridge Children's Hospital and Health Center
- Northwest Medical Specialties PLLC
- Madigan Army Medical Center
- West Virginia University Healthcare
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Marinette
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- Alberta Children's Hospital
- University of Alberta Hospital
- British Columbia Children's Hospital
- CancerCare Manitoba
- Janeway Child Health Centre
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Children's Hospital
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
- San Jorge Children's Hospital
- University Pediatric Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Regimen A (VDC/IE)
Regimen B (VDC/IE + ganitumab)
See Design Details.
INDUCTION THERAPY: Patients receive Induction therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11. LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy. CONSOLIDATION THERAPY: Patients receive Consolidation therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15. METASTATIC SITE IRRADIATION: Patients with lung metastases undergo whole lung radiation and patients with bone metastases undergo definitive SBRT or EBRT. MAINTENANCE: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes every 3 weeks for 8 cycles.