High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma

Sarcoma Clinical Trial

Official title: Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma

Status Completed

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as vincristine, irinotecan, ifosfamide, etoposide, doxorubicin, cyclophosphamide, and dactinomycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving high-dose combination chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase III trial is studying how well giving high-dose combination chemotherapy together with radiation therapy works in treating patients with newly diagnosed metastatic rhabdomyosarcoma or ectomesenchymoma.

Clinical Trial Description

OBJECTIVES:

Primary

• Improve the early disease control interval for patients with newly diagnosed, high-risk, metastatic rhabdomyosarcoma or ectomesenchymoma using intensive, interval-compression therapy (comprising vincristine, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin) that permits maximal early exposure to known effective agents.

• Determine the feasibility and assess immediate- and short-term side effects of concurrent irinotecan hydrochloride and radiotherapy in these patients.

Secondary

• Expand the available data for response to irinotecan hydrochloride and vincristine in previously untreated patients with high-risk rhabdomyosarcoma.

• Evaluate, prospectively, and validate gene expression values with the intent to define the best diagnostic predictors and more powerful prognostic classifiers.

OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are stratified according to prognostic factors predictive of outcome (e.g. histology, bone/bone marrow involvement, and number of metastatic sites).

Patients receive high-dose chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; and ifosfamide IV over 1 hour and etoposide IV over 30-60 minutes on days 1-5 of weeks 9, 13, 17, 26, and 30. Patients also receive doxorubicin hydrochloride IV continuously over 24 hours on days 1 and 2 of weeks 7*, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; and dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44 in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously in weeks 7-9, 11-13, 15-17, 22, 26, 28-30, 32, 33, 35, 38, and 41-44 beginning 24-36 hours after the last chemotherapy dose and continuing until blood counts recover.

NOTE: *Patients undergoing early radiotherapy for intracranial extension do not receive doxorubicin in week 7.

Beginning at week 20 (or week 1 for patients with parameningeal tumors with intracranial extension [or spinal cord compression] requiring emergency radiotherapy), patients also undergo radiotherapy once a day, 5 days a week, for approximately 5½ weeks. Some patients may also undergo second-look surgery.

After completion of study treatment, patients are followed periodically for ≥ 10 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study. ;

Related Conditions & MeSH terms

• Rhabdomyosarcoma
• Sarcoma

• NCT number: NCT00354744
• Study type: Interventional
• Source: Children's Oncology Group
• Status: Completed
• Phase: Phase 3
• Start date: July 2006
• Completion date: June 30, 2019