Combination Chemotherapy Plus Dexrazoxane in Treating Patients With Newly Diagnosed Nonmetastatic Osteosarcoma

Sarcoma Clinical Trial

Official title: Protocol for Patients With Newly-Diagnosed Non-Metastatic Osteosarcoma - A POG/CCG Pilot Intergroup Study

Status Completed

Clinical Trial Summary

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 may kill more tumor cells. Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase III trial to study the effectiveness of three combination chemotherapy regimens plus dexrazoxane in treating patients who have newly diagnosed nonmetastatic osteosarcoma.

Clinical Trial Description

OBJECTIVES: I. Compare the efficacy of three intensification regimens (doxorubicin vs doxorubicin plus ifosfamide vs doxorubicin plus ifosfamide and etoposide) in patients with newly diagnosed, previously untreated, nonmetastatic osteosarcoma. II. Determine the effect of postoperative dose intensification on outcome in patients with standard response to preoperative chemotherapy. III. Determine the effect of dexrazoxane cardioprotection during standard induction therapy on histologic response in these patients. IV. Evaluate biological factors that may predict outcome in these patients. V. Determine the safety of dexrazoxane administered with doxorubicin in combination with cisplatin or cisplatin and ifosfamide in these patients. VI. Determine the effect of dexrazoxane on cytotoxicity as measured by tumor necrosis at definitive surgery in these patients. VII. Assess the feasibility of administering doxorubicin with dexrazoxane cardioprotection or high dose ifosfamide with etoposide to standard risk patients who are also receiving methotrexate and cisplatin.

OUTLINE: This is a multicenter study. Patients are enrolled sequentially on 1 of 3 pilot intensification regimens. After surgery to completely remove the primary tumor, patients are assigned to 1 of 2 adjuvant chemotherapy groups based on percent necrosis at limb salvage. Pilot 1: (Closed to accrual as of 6/2/2000) Patients receive dexrazoxane IV followed immediately by doxorubicin IV over 20 minutes plus cisplatin IV over 4 hours on days 1 and 2 of weeks 1 and 6. Methotrexate IV over 4 hours is administered 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 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 for 6 courses. Pilot 2: Patients receive preoperative therapy comprised of dexrazoxane, doxorubicin, and methotrexate as in pilot 1. Ifosfamide IV over 4 hours is also administered 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, and doxorubicin 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, and doxorubicin 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. Pilot 3: (Open to accrual as of 6/2/2000) Patients receive preoperative therapy comprised of methotrexate, dexrazoxane, 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, 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 and doxorubicin are administered on weeks 17, 20, 30, and 33. Patients are followed every 3 months for 1 year, every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 180 patients will be accrued for this study within 2 years. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Toxicity
• Osteosarcoma
• Sarcoma

• NCT number: NCT00003937
• Study type: Interventional
• Source: Children's Oncology Group
• Status: Completed
• Phase: Phase 3
• Start date: September 1999
• Completion date: June 2008