Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma
Localized Extraskeletal Ewing Sarcoma, Peripheral Primitive Neuroectodermal Tumor of Bone, Peripheral Primitive Neuroectodermal Tumor of Soft Tissues
About this trial
This is an interventional treatment trial for Localized Extraskeletal Ewing Sarcoma
Eligibility Criteria
Inclusion Criteria:
Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue are eligible for this study; note:
- For the purpose of this study, chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology or ipsilateral pleural based secondary tumor nodules will be considered localized disease
- Patients with regional node involvement, based on clinical suspicion confirmed by pathologic documentation are considered to be non-metastatic
- Patients with discontinuous osseous lesions within the same bone are considered to be non-metastatic
- Tumors arising in the bony skull (extra-dural) are considered to be extracranial
- Patient eligibility will be based on a diagnosis of Ewing sarcoma or PNET by institutional pathologist
- No prior chemotherapy or radiation therapy is allowed; 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 unplanned excision was attempted or accomplished as long as adequate imaging was obtained prior to surgery
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or serum creatinine based on age/gender as follows:
- 1 month to < 6 months: 0.4 mg/dL
- 6 months to < 1 year: 0.5 mg/dL
- 1 to < 2 years: 0.6 mg/dL
- 2 to < 6 years: 0.8 mg/dL
- 6 to < 10 years: 1 mg/dL
- 10 to < 13 years: 1.2 mg/dL
- 13 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
- >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
- Total bilirubin < 1.5 x upper limit of normal (ULN) for age
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 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 must have no evidence of metastatic disease; metastatic disease are lesions which are discontinuous from the primary tumor, are not regional lymph nodes and do not share a body cavity with the primary tumor; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be taken
- Skeletal lesions in adjacent bones (trans-articular)
- Contralateral pleural effusion and 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 biopsied and negative for Ewing's
- Biopsies of solitary nodule =< 0.5 cm or multiple nodules =< 0.3 cm are not required but if performed and positive indicate metastatic disease
- Patients whose tumors arise in the dural and intra-dural soft tissues of the cranium and spine are not eligible
- Patients with pathologic diagnoses other than Ewing sarcoma will be excluded
- Patients diagnosed with Ewing Sarcoma as a second malignant neoplasm are not eligible if they have received chemotherapy or radiation for the treatment of their primary malignancy
- Pregnant women will not be entered on this study; pregnancy tests must be obtained in female patients who are post-menarchal; lactating females may not participate unless they have agreed not to breastfeed their infants; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of the study treatment
- 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
Sites / Locations
- Children's Hospital of Alabama
- University of Alabama at Birmingham Cancer Center
- USA Health Strada Patient Care Center
- Providence Alaska Medical Center
- Phoenix Childrens Hospital
- Banner University Medical Center - Tucson
- Arkansas Children's Hospital
- University of Arkansas for Medical Sciences
- 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
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Cedars Sinai Medical Center
- Mattel Children's Hospital UCLA
- UCLA / Jonsson Comprehensive Cancer Center
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- 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
- Children's Hospital Colorado
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
- Connecticut Children's Medical Center
- Yale University
- Alfred I duPont Hospital for Children
- MedStar Georgetown University Hospital
- Children's National Medical Center
- Broward Health Medical Center
- Lee Memorial Health System
- 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
- Miami Cancer Institute
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Clinic - Orlando
- Orlando Health Cancer Institute
- 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
- University of Hawaii Cancer Center
- Kapiolani Medical Center for Women and Children
- Tripler Army Medical Center
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- Northwestern University
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Loyola University Medical Center
- Advocate Children's Hospital-Oak Lawn
- Advocate Children's Hospital-Park Ridge
- Advocate Lutheran General Hospital
- Saint Jude Midwest Affiliate
- Saint John's Hospital
- Southern Illinois University School of Medicine
- Memorial Medical Center
- Indiana University/Melvin and Bren Simon Cancer Center
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- Blank Children's Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Tulane University Health Sciences Center
- 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
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Michigan State University Clinical Center
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Bronson Methodist Hospital
- Beaumont Children's Hospital-Royal Oak
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Columbia Regional
- Children's Mercy Hospitals and Clinics
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Children's Hospital and Medical Center of Omaha
- University of Nebraska Medical Center
- University Medical Center of Southern Nevada
- Sunrise Hospital and Medical Center
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Nevada Cancer Research Foundation NCORP
- Saint Mary's Regional Medical Center
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Hackensack University Medical Center
- Saint Barnabas 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
- Overlook Hospital
- University of New Mexico Cancer Center
- Albany Medical Center
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- 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
- Novant Health Presbyterian Medical Center
- Duke University Medical Center
- Wake Forest University Health Sciences
- Sanford Broadway Medical Center
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- 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
- Mercy Children's Hospital
- University of Oklahoma Health Sciences Center
- Natalie Warren Bryant Cancer Center at Saint Francis
- Providence Saint Vincent Medical Center
- Legacy Emanuel Children's Hospital
- Legacy Emanuel Hospital and Health Center
- Oregon Health and Science University
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Penn State Children's Hospital
- Children's Hospital of Philadelphia
- Fox Chase Cancer Center
- 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
- BI-LO Charities Children's Cancer Center
- Greenville Cancer Treatment Center
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- East Tennessee Childrens Hospital
- Saint Jude Children's Research Hospital
- Vanderbilt University/Ingram Cancer Center
- Dell Children's Medical Center of Central Texas
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- El Paso Children's Hospital
- Brooke Army Medical Center
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- M D Anderson Cancer Center
- Covenant Children's Hospital
- 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
- University of Vermont and State Agricultural College
- University of Virginia Cancer Center
- Inova Fairfax Hospital
- Children's Hospital of The King's Daughters
- Naval Medical Center - Portsmouth
- Virginia Commonwealth University/Massey Cancer Center
- Carilion Children's
- Seattle Children's Hospital
- University of Washington Medical Center - Montlake
- Providence Sacred Heart Medical Center and Children's Hospital
- Mary Bridge Children's Hospital and Health Center
- Madigan Army Medical Center
- United Hospital Center
- West Virginia University Charleston Division
- West Virginia University Healthcare
- Camden Clark Medical Center
- Saint Vincent Hospital Cancer Center Green Bay
- University of Wisconsin Carbone Cancer Center
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- Medical College of Wisconsin
- John Hunter Children's Hospital
- Sydney Children's Hospital
- The Children's Hospital at Westmead
- Royal Brisbane and Women's Hospital
- Royal Children's Hospital-Brisbane
- Queensland Children's Hospital
- Women's and Children's Hospital-Adelaide
- Princess Margaret Hospital for Children
- 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
- Allan Blair Cancer Centre
- Saskatoon Cancer Centre
- Centre Hospitalier Universitaire de Quebec
- Starship Children's Hospital
- Christchurch Hospital
- San Jorge Children's Hospital
- King Faisal Specialist Hospital and Research Centre
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (combination chemotherapy)
Arm B (combination chemotherapy, topotecan hydrochloride)
INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6, 9, and 10; doxorubicin hydrochloride IV over 1-15 minutes (or as per institutional policies up to 60-minutes) on days 1 and 2 and cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 5, and 9; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 7, and 11. CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7, 8, 9, 10, 13, 14, 17, 18, 21, and 22; doxorubicin hydrochloride IV on days 1 and 2 in weeks 1 and 9; cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 7, 9, 13, 17, and 21; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 5, 11, 15, and 19. Patients received Dexrazoxane with doxorubicin hydrochloride in weeks 1 and 9.
INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6, 9, 10, 11 and 12; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 9; cyclophosphamide IV over 15-30 minutes on days 1-5 in weeks 1 and 9, and over 30-60 minutes on day 1 of weeks 5 and 11; ifosfamide and etoposide as in arm A; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 5 and 11. CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7-10, 13-16, 19, and 20; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1, 7, and 15; cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1, 7, and 15, and over 30-60 minutes on day 1 in weeks 9, 13, and 19; ifosfamide IV over 1 hour and etoposide IV over 1- 2 hours on days 1-5 in weeks 3, 5, 11, 17, and 21; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 9,13, and 19. Patients received Dexrazoxane with doxorubicin hydrochloride in weeks 13 and 19.