Combination Chemotherapy Plus Dexrazoxane in Treating Patients With Newly Diagnosed Nonmetastatic Osteosarcoma
Cardiac Toxicity, Sarcoma
About this trial
This is an interventional treatment trial for Cardiac Toxicity focused on measuring localized osteosarcoma, cardiac toxicity
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically proven newly diagnosed moderate or high grade osteosarcoma without metastases No prior treatment, including complete resection No parosteal or periosteal sarcoma No osteosarcoma associated with Paget's disease No nonresectable tumors or tumors that may result in marginal or interlesion resection Must be enrolled on protocol POG-9851 PATIENT CHARACTERISTICS: Age: 30 and under Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times normal SGOT no greater than 3 times normal Renal: Creatinine normal Phosphate at least 3.0 mg/dL without supplementation Cardiovascular: Shortening fraction at least 28% by echocardiogram If echocardiogram unsatisfactory, must have ejection fraction at least 50% No history of pericarditis or myocarditis No symptomatic arrhythmia or symptomatic cardiac conduction disturbances PRIOR CONCURRENT THERAPY: See Disease Characteristics Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics
Sites / Locations
- University of Alabama at Birmingham Comprehensive Cancer Center
- MBCCOP - Gulf Coast
- Arizona Cancer Center
- University of Arkansas for Medical Sciences
- University of California San Diego Cancer Center
- Long Beach Memorial Medical Center
- Children's Hospital Los Angeles
- Jonsson Comprehensive Cancer Center, UCLA
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital at Stanford
- Sutter Cancer Center
- University of California Davis Medical Center
- Kaiser Permanente-Southern California Permanente Medical Group
- Children's Hospital and Health Center
- UCSF Cancer Center and Cancer Research Institute
- Kaiser Permanente Medical Center - Santa Clara
- David Grant Medical Center
- Children's Hospital of Denver
- Yale Comprehensive Cancer Center
- Children's National Medical Center
- Walter Reed Army Medical Center
- Shands Hospital and Clinics, University of Florida
- Nemours Children's Clinic
- Sylvester Cancer Center, University of Miami
- Miami Children's Hospital
- Baptist Hospital of Miami
- Walt Disney Memorial Cancer Institute
- All Children's Hospital
- CCOP - Florida Pediatric
- St. Mary's Hospital
- Emory University Hospital - Atlanta
- Cancer Research Center of Hawaii
- Tripler Army Medical Center
- Rush-Presbyterian-St. Luke's Medical Center
- Children's Memorial Hospital, Chicago
- University of Chicago Cancer Research Center
- Hope Children's Hospital
- CCOP - Illinois Oncology Research Association
- Saint Jude Midwest Affiliate
- Indiana University Cancer Center
- Holden Comprehensive Cancer Center at The University of Iowa
- University of Kansas Medical Center
- CCOP - Wichita
- Via Christi Regional Medical Center
- MBCCOP - LSU Health Sciences Center
- Tulane University School of Medicine
- CCOP - Ochsner
- Eastern Maine Medical Center
- Maine Children's Cancer Program
- Marlene & Stewart Greenebaum Cancer Center, University of Maryland
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Boston Floating Hospital Infants and Children
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- University of Massachusetts Memorial Medical Center
- University of Michigan Comprehensive Cancer Center
- Children's Hospital of Michigan
- St. John's Hospital and Medical Center
- Hurley Medical Center
- CCOP - Kalamazoo
- University of Minnesota Cancer Center
- Mayo Clinic Cancer Center
- University of Mississippi Medical Center
- Keesler Medical Center - Keesler AFB
- University of Missouri-Columbia Hospital and Clinics
- Children's Mercy Hospital
- Cardinal Glennon Children's Hospital
- Washington University School of Medicine
- University of Nebraska Medical Center
- Norris Cotton Cancer Center
- CCOP - Northern New Jersey
- Hackensack University Medical Center
- Cancer Institute of New Jersey
- University of New Mexico School of Medicine
- Roswell Park Cancer Institute
- Schneider Children's Hospital
- NYU School of Medicine's Kaplan Comprehensive Cancer Center
- Memorial Sloan-Kettering Cancer Center
- Mount Sinai School of Medicine
- Herbert Irving Comprehensive Cancer Center
- University of Rochester Cancer Center
- State University of New York Health Sciences Center - Stony Brook
- State University of New York - Upstate Medical University
- Mission Saint Joseph's Health System
- Lineberger Comprehensive Cancer Center, UNC
- Carolinas Medical Center
- Presbyterian Healthcare
- Duke Comprehensive Cancer Center
- East Carolina University School of Medicine
- Comprehensive Cancer Center at Wake Forest University
- Veterans Affairs Medical Center - Fargo
- CCOP - Merit Care Hospital
- Children's Hospital Medical Center - Cincinnati
- Ireland Cancer Center
- Children's Hospital of Columbus
- Oklahoma Memorial Hospital
- Natalie Warren Bryant Cancer Center
- Doernbecher Children's Hospital
- CCOP - Columbia River Program
- Legacy Emanuel Hospital and Health Center
- Children's Hospital of Philadelphia
- St. Christopher's Hospital for Children
- Children's Hospital of Pittsburgh
- Medical University of South Carolina
- Children's Hospital of Greenville Hospital System
- James H. Quillen College of Medicine
- Saint Jude Children's Research Hospital
- Vanderbilt-Ingram Cancer Center
- Texas Oncology P.A.
- Medical City Dallas Hospital
- Simmons Cancer Center - Dallas
- University of Texas Medical Branch
- University of Texas - MD Anderson Cancer Center
- Baylor College of Medicine
- San Antonio Military Pediatric Cancer and Blood Disorders Center
- MBCCOP - South Texas Pediatric
- University of Texas Health Science Center at San Antonio
- Scott and White Clinic
- Vermont Cancer Center
- Cancer Center at the University of Virginia
- Inova Fairfax Hospital
- Naval Medical Center, Portsmouth
- Massey Cancer Center
- Carilion Roanoke Community Hospital
- Children's Hospital and Regional Medical Center - Seattle
- Fred Hutchinson Cancer Research Center
- Madigan Army Medical Center
- West Virginia University Medical School-Charleston
- West Virginia University Hospitals
- St. Vincent Hospital
- University of Wisconsin Comprehensive Cancer Center
- Midwest Children's Cancer Center
- Royal Children's Hospital
- Princess Margaret Hospital for Children
- Alberta Children's Hospital
- Cross Cancer Institute
- British Columbia Children's Hospital
- IWK Health Centre
- Children's Hospital
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- McGill University Health Center - Montreal Children's Hospital
- Hopital Sainte Justine
- Centre Hospitalier de L'Universite Laval
- Academisch Ziekenhuis Groningen
- San Jorge Childrens Hospital
- Swiss Pediatric Oncology Group Bern
- Clinique de Pediatrie
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Pilot 1 - Doxorubicin Intensification without Ifosfamide
Pilot 2 - Doxorubicin Intensification with Ifosfamide
Pilot 3 - Ifosfamide/Etoposide Intensification
Dexrazoxane hydrochloride IV followed by doxorubicin hydrochloride IV plus cisplatin IV on days 1 and 2 of weeks 1 and 6. Methotrexate IV on day 1 of weeks 4, 5, 9, and 10. Patients undergo surgery on week 11. Adjuvant chemotherapy begins on day 1 of week 13. Group 1 (good response to neoadjuvant chemotherapy): Patients receive methotrexate IV over 4 hours every 3 weeks for 6 courses, beginning on week 13. Patients also receive dexrazoxane and doxorubicin hydrochloride every 3 weeks for 4 courses, beginning on week 14. Cisplatin is administered with the first 2 courses of dexrazoxane and doxorubicin. Group 2 (standard response to neoadjuvant chemotherapy): Patients receive methotrexate and cisplatin as in group 1 plus dexrazoxane and doxorubicin hydrochloride for 6 courses.
Preoperative therapy comprised of dexrazoxane hydrochloride, doxorubicin hydrochloride, and methotrexate as in pilot 1. Ifosfamide IV on days 1-5 of week 1. Patients undergo surgery on week 11, then begin adjuvant chemotherapy on week 13. Group 1: Patients receive methotrexate, dexrazoxane hydrochloride, and doxorubicin hydrochloride as in pilot 1, group 1. Ifosfamide is also administered on weeks 14 and 20. Cisplatin is administered on weeks 17, 23, and 26. Group 2: Patients receive methotrexate, dexrazoxane hydrochloride, and doxorubicin hydrochloride as in pilot 1, group 2. Ifosfamide is administered on weeks 14, 20, 26, and 31. Cisplatin is administered on weeks 17, 23, and 29
Preoperative therapy comprised of methotrexate, dexrazoxane hydrochloride, doxorubicin, ifosfamide, and cisplatin as in pilot 2. Patients undergo surgery on week 11, then begin adjuvant chemotherapy on week 13. Group 1: Patients receive methotrexate, dexrazoxane hydrochloride, doxorubicin, ifosfamide, and cisplatin as in pilot 2, group 1. Group 2: Patients receive methotrexate on weeks 13, 19, 29, 32, 35, and 36, high dose ifosfamide and etoposide IV over 4 hours on days 1-5 of weeks 14, 23, and 26, and cisplatin on weeks 20, 30, and 33. Dexrazoxane hydrochloride and doxorubicin hydrochloride are administered on weeks 17, 20, 30, and 33