Trial Information

MMT 98 Study For Metastatic Disease Rhabdomyosarcoma And Other Malignant Soft Tissue Sarcoma Of Childhood

OBJECTIVES:

- Determine the overall survival of children with metastatic rhabdomyosarcoma or other
malignant mesenchymal tumors treated with one of two different chemotherapy regimens
based upon risk group.

- Determine the role of low-intensity maintenance chemotherapy after intensive
conventional chemotherapy in standard-risk children.

- Determine the value of a therapeutic window in high-risk children.

- Determine the role of sequential high-dose chemotherapy with peripheral blood stem cell
transplantation in achieving complete response in high-risk children.

- Determine the complete response, overall survival, and event-free survival in high-risk
children.

OUTLINE: This is a multicenter study. Patients are stratified according to risk group
(standard vs high).

Standard-risk patients:

- Initial chemotherapy: Patients receive vincristine IV on day 1 for weeks 1-7. Patients
also receive dactinomycin IV on day 1 and ifosfamide IV over 1 hour on days 1-3 of week
1. Patients then receive carboplatin IV over 1 hour and epirubicin IV over 6 hours on
day 1 of week 4. Patients then receive ifosfamide IV over 1 hour and etoposide IV over
4 hours on days 1-3 of week 7. Treatment repeats every 8 weeks for 3 courses in the
absence of disease progression or unacceptable toxicity. After the second course,
patients with less than 50% partial response (PR) are removed from study.

Patients with parameningeal disease undergo radiotherapy 5 days a week for about 8 weeks
beginning at week 9.

- Maintenance chemotherapy: Patients receive cyclophosphamide IV over 1 hour, vincristine
IV, and dactinomycin IV on day 1. Treatment repeats every 3 weeks for 9 courses in the
absence of disease progression or unacceptable toxicity.

Patients who remain in PR at week 17 undergo radiotherapy for about 9 weeks beginning at
week 18.

High-risk patients:

- Initial chemotherapy: Patients receive window study drug carboplatin IV over 1 hour or
doxorubicin on day 1. Treatment repeats every 3 weeks for 2 courses.

Patients receive high-dose cyclophosphamide IV over 1 hour on days 1-3 of week 7. Beginning
on day 8, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) daily until day 13.
Patients may undergo peripheral blood stem cell (PBSC) collection.

Patients receive high-dose etoposide IV over 24 hours on days 15-17. Beginning on day 22,
patients receive G-CSF IV or SC daily until day 27.

Patients receive high-dose cyclophosphamide IV over 1 hour on days 29-31. Beginning on day
36, patients receive G-CSF IV or SC daily until day 42. Patients may undergo PBSC collection
if not previously performed. Patients who achieve complete response (CR) are removed from
study.

Patients receive high-dose carboplatin IV over 1 hour on days 44-48. Patients undergo PBSC
reinfusion on day 52. Beginning on day 55, patients receive G-CSF IV or SC daily until blood
counts recover.

- Maintenance chemotherapy: Patients receive maintenance chemotherapy comprising
cyclophosphamide, vincristine, and dactinomycin in the same manner as the standard-risk
patients.

Patients with parameningeal disease and those not achieving CR undergo radiotherapy
beginning at week 17. Patients achieving CR, unless metastatic disease is resected, undergo
radiotherapy beginning on week 15.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months
for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 8-30 standard-risk patients will be accrued for this study
within 4 years. A total of 15-75 high-risk patients will be accrued for this study within
4-5 years.