Combination Chemotherapy and Surgery in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug or combining chemotherapy with surgery may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and surgery in treating patients who have newly diagnosed metastatic osteosarcoma.
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: trimetrexate glucuronate
Procedure: surgical procedure
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase II Window Study of Trimetrexate With Simultaneous Leucovorin Protection in the Treatment of Newly Diagnosed Patients With Metastatic Osteosarcoma|
|Study Start Date:||December 1998|
|Study Completion Date:||March 2000|
|Primary Completion Date:||March 2000 (Final data collection date for primary outcome measure)|
OBJECTIVES: I. Determine the efficacy of oral trimetrexate glucuronate with simultaneous leucovorin calcium protection in patients with newly diagnosed metastatic osteogenic sarcoma. II. Evaluate the toxicity of this regimen when administered prior to and following standard chemotherapy in patients with osteogenic sarcoma. III. Correlate response with in vitro determinants of chemotherapy resistance in tumor samples obtained from these patients.
OUTLINE: Patients receive induction therapy of oral trimetrexate glucuronate (TMTX) and leucovorin calcium every 12 hours for 21 days (weeks 0-2). Patients receive leucovorin calcium for 3 additional days after the last dose of TMTX. If age prevents compliance with oral administration, patients receive TMTX IV and leucovorin calcium IV. Patients undergo definitive surgery 7-10 days after the induction therapy (week 4). Patients undergo surgery for metastatic disease, if indicated, as soon as possible following recovery from definitive surgery. Patients then receive maintenance therapy every 3 weeks for 8-9 months according to the following schedule: Patients receive ifosfamide IV over 1 hour 4 times daily on days 1-4 plus doxorubicin IV over 48 hours on days 1-2 in weeks 6, 14, and 22, and ifosfamide alone in week 30. Patients receive cisplatin IV over 4 hours for 1 day, plus doxorubicin IV over 48 hours for 2 days beginning on the same day as the first dose of cisplatin, in weeks 10, 18, and 26. Patients receive cisplatin alone in week 34. Patients receive filgrastim subcutaneously daily for 2 weeks starting 24 hours after the completion of each course of ifosfamide and cisplatin therapy. Patients receive methotrexate IV over 4 hours for 1 day, plus oral leucovorin calcium every 6 hours for at least 10 doses beginning 20 hours after the last dose of methotrexate, in weeks 9, 13, 17, 21, 25, 29, 33, and 37. In severe cases, patients receive leucovorin calcium IV over 24 hours. Patients who respond to induction therapy receive a second course of the same therapy in weeks 38-40. Patients are followed every 4 months for 1 year, then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study over 2-3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003776
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|Study Chair:||Richard Gorlick, MD||Memorial Sloan Kettering Cancer Center|