Trial Information

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

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.