Trial Information

Treatment of High Risk Central Nervous System Embryonal Tumors With Conventional Radiotherapy and Intensive Consolidation Chemotherapy With Peripheral Blood Progenitor Cell (PBSC) Support

OBJECTIVES:

- Determine the safety of postradiotherapy high-dose consolidation chemotherapy with
peripheral blood stem cell (PBSC) support in patients with high-risk primitive
neuroectodermal tumors.

- Determine the safety of delaying radiotherapy by approximately one month in these
patients.

- Determine the maximum tolerated dose of thiotepa in these patients.

- Determine the toxic effects of intensive chemotherapy with PBSC support in these
patients.

- Assess the time to hematopoietic recovery after PBSC infusion when intensive
chemotherapy is used after craniospinal radiotherapy in these patients.

- Determine the overall and event-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of thiotepa during consolidation therapy.

- Induction: Within 31 days of initial surgery, patients receive induction therapy
comprising vincristine IV on day 0, cyclophosphamide IV over 2 hours on days 0 and 1,
and filgrastim (G-CSF) subcutaneously (SC) beginning on day 2 and continuing for at
least 7-10 days. Peripheral blood stem cells (PBSC) are then collected.

- Chemoradiotherapy: After blood cell counts recover, and within 28 days of starting
induction, patients begin chemoradiotherapy. Patients receive vincristine IV once
weekly for 8 doses. Radiotherapy is administered 5 days a week, for 6 weeks, beginning
within the same week as the start of vincristine.

- Consolidation: Therapy begins 4-6 weeks after the last radiation treatment in the
absence of disease progression. The first and third course are the same and comprise
vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, thiotepa IV over 3
hours on days 2-4, and G-CSF SC daily beginning on day 7. PBSC are reinfused on day 7.
The second course comprises vincristine IV on day 0, carboplatin IV over 1 hour on days
0 and 1, cyclophosphamide IV over 2 hours on days 2 and 3, and G-CSF SC daily beginning
on day 5. PBSC are reinfused on day 5. Each course lasts 21 days.

For consolidation therapy, cohorts of 6-12 patients each receive escalating doses of
thiotepa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose at which no more than 2 of 12 patients experience dose-limiting toxicity.

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

PROJECTED ACCRUAL: A total of 24-56 patients will be accrued for this study.