Trial Information

An Intergroup Pilot Study of Concurrent Carboplatin, Vincristine and Radiotherapy Followed by Adjuvant Chemotherapy in Patients With Newly Diagnosed High-Risk Central Nervous System Embryonal Tumors

OBJECTIVES:

- Determine the feasible dose and duration of carboplatin combined with craniospinal and
local radiotherapy and adjuvant chemotherapy in children with newly diagnosed,
high-risk CNS embryonal tumors (Phase I completed as of 11-25-03).

- Determine the feasibility of administering cyclophosphamide and vincristine with or
without cisplatin after concurrent carboplatin, vincristine, and radiotherapy in these
patients.

- Determine the overall and individual toxicity rates of this regimen in these patients.

- Determine the complete response rate in patients treated with this regimen.

- Obtain preliminary estimates of event-free survival of patients treated with this
regimen.

- Determine the prognostic significance of enhancing tumor after completion of
radiotherapy on event-free survival of these patients.

OUTLINE: This is a pilot, dose-escalation study of carboplatin. (Phase I completed as of
11-25-03.)

Within 31 days of definitive surgery, all patients receive vincristine IV weekly for 6 weeks
and carboplatin IV over 15-20 minutes (after completion of vincristine infusion) 5 days a
week for 6 weeks. Patients undergo radiotherapy (1-4 hours after carboplatin infusion) 5
days a week for 6 weeks.

Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which no more than 3 of 12
patients experience dose-limiting toxicity. (Phase I completed as of 11-25-03.)

At 6 weeks after completion of radiotherapy, patients are assigned to arm II for
adjuvant/maintenance chemotherapy. (Arm I closed to accrual as of 11-25-03.)

- Arm I (closed to accrual as of 11-25-03): Patients receive cyclophosphamide IV over 1
hour on days 0 and 1, vincristine IV on days 0 and 7, and filgrastim (G-CSF) IV or
subcutaneously (SC) beginning on day 2 and continuing for at least 10 days until blood
counts recover.

- Arm II: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2, vincristine
IV on days 0 and 7, cisplatin IV over 6 hours on day 0, and G-CSF IV or SC beginning on
day 3 and continuing for at least 10 days until blood counts recover.

In both arms, adjuvant/maintenance chemotherapy repeats every 4 weeks for 6 courses.

Patients are followed every 3 months for 8 months, every 4 months for 1 year, every 6 months
for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.