NCT00003955

Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Metastatic Rhabdomyosarcoma or Sarcoma

A Phase II "Up-Front Window Study" of Irinotecan (CPT-11) Followed by Multimodal, Multiagent, Therapy for Selected Children and Adolescents With Newly Diagnosed Stage 4/Clinical Group IV Rhabdomyosarcoma: An IRS-V Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 77 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 49 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy combined with radiation therapy in treating patients who have metastatic rhabdomyosarcoma or sarcoma.

Detailed description

OBJECTIVES: * Determine the response rate of patients with newly diagnosed high-risk metastatic stage IV/clinical group IV rhabdomyosarcoma treated with upfront window therapy comprising irinotecan and vincristine. * Determine the toxic effects of this regimen in these patients. * Determine the toxic effects of this regimen when given in alternating courses with vincristine, dactinomycin, and cyclophosphamide (VAC) as continuation therapy in patients with partial or complete response. * Determine the overall and failure-free survival of patients treated with irinotecan and vincristine followed by VAC alone or VAC alternating with vincristine and irinotecan plus radiotherapy. * Determine the pharmacokinetics of irinotecan and vincristine in these patients. OUTLINE: * Upfront window therapy: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 60 minutes on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 2 courses. Patients experiencing partial or complete response proceed to regimen A. Patients experiencing stable or progressive disease proceed to regimen B. * Regimen A: Patients receive vincristine IV over 1 minute weekly on weeks 6-13, 15-19, 23-27, 29, 32-35, 38-39, and 41; dactinomycin IV over 1 minute weekly on weeks 6, 12, 23, 29, 35, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 12, 16, 19, 23, 29, 35, and 41. Patients also receive irinotecan IV over 1 hour daily, 5 days a week, on weeks 9, 10, 26, 27, 32, 33, 38, and 39 and undergo radiotherapy daily, 5 days a week, on weeks 15-22. * Regimen B: Patients receive vincristine as in regimen A; dactinomycin IV over 1 minute weekly on weeks 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41 and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients receive radiotherapy as in regimen A. Patients who do not receive upfront window irinotecan/vincristine therapy are treated with standard therapy. * Standard therapy: Patients receive vincristine IV over 1 minute weekly on weeks 0-13, 15-19, 23-27, 29, 32-35, 38, and 41; dactinomycin IV over 1 minute weekly on weeks 0, 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 0, 3, 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients without evidence of intracranial extension receive radiotherapy once daily, 5 days a week, during weeks 15-22. Patients with evidence of intracranial extension, or who require emergency radiotherapy, receive radiotherapy during weeks 0-6. Dactinomycin is withheld during radiotherapy. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) beginning 24 hours after completion of each course of chemotherapy and continuing until blood counts recover. Alternatively, patients may receive pegfilgrastim SC beginning 24-36 hours after completion of each course of chemotherapy and continuing until blood counts recover. Patients are followed every 2 months for 1 year, every 4 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 9-24 months.

Conditions

• Sarcoma

Interventions

Type	Name	Description
BIOLOGICAL	dactinomycin
BIOLOGICAL	filgrastim
BIOLOGICAL	pegfilgrastim
BIOLOGICAL	sargramostim
DRUG	cyclophosphamide
DRUG	irinotecan hydrochloride
DRUG	vincristine sulfate
RADIATION	radiation therapy

Timeline

• Start date: 1999-09-01
• Primary completion: 2005-01-01
• Completion: 2009-10-01
• First posted: 2003-01-27
• Last updated: 2014-02-14

Locations

237 sites across 7 countries: United States, Australia, Canada, Netherlands, New Zealand, Puerto Rico, Switzerland