Trial Information

Treatment of Newly Diagnosed Medulloblastoma and Supratentorial PNET in Patients At Least 3 Years With a Phase II Topotecan Window (High-Risk Patients Only), Risk-Adapted Radiation Therapy, and Dose-Intensive Chemotherapy With Peripheral Blood Stem Cell Support

OBJECTIVES:

- Estimate the response rate to topotecan in children with newly diagnosed
medulloblastoma or supratentorial primitive neuroectodermal tumors who have measurable
residual disease after surgery. (Topotecan window closed to accrual 9/10/2001)

- Determine the feasibility of four courses of high-dose chemotherapy (vincristine,
cisplatin, and cyclophosphamide) with peripheral blood stem cell support after
craniospinal irradiation (CSI) in these patients.

- Estimate the 5-year overall survival and progression-free survival in patients treated
with risk-adapted CSI and high-dose chemotherapy.

- Compare changes in intellectual functioning in patients treated with reduced-dose vs
standard-dose CSI.

- Estimate the incidence of ototoxicity associated with risk-adapted CSI and posterior
fossa boost(s) given by 3-D conformal radiotherapy technique combined with amifostine
and cisplatin.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups based
on risk status.

- Group 1 (average-risk): Patients receive filgrastim (G-CSF) subcutaneously (SC) or IV
daily until peripheral blood stem cells (PBSC) are harvested. PBSC are harvested when
blood counts recover. Patients then receive craniospinal irradiation (CSI) 5 days a
week for 6 weeks. Beginning 6 weeks after completion of CSI, patients receive high-dose
chemotherapy comprising vincristine IV followed by cisplatin IV over 6 hours on day -4
and cyclophosphamide IV over 1 hour on days -3 and -2. Patients receive amifostine IV
over 1 minute a maximum of 5 minutes prior to cisplatin infusion and then 3 hours into
cisplatin infusion. PBSC are reinfused on day 0. Patients receive G-CSF SC beginning on
day 1 and continuing for a minimum of 7 days or until blood counts recover. Vincristine
IV is administered on day 6. G-CSF is stopped 48 hours prior to beginning subsequent
courses of chemotherapy. High-dose chemotherapy repeats every 4 weeks for 4 courses.

- Group 2 (high-risk): Patients receive topotecan IV over 4 hours on days 1-5 and G-CSF
SC or IV beginning 24 hours after completion of the first course of topotecan and
continuing until PBSC are harvested. Treatment repeats every 3 weeks for 2 courses. If
an adequate number of PBSC are not harvested, the patient undergoes a second harvest of
PBSC after the second course of topotecan. Patients then receive CSI, high-dose
chemotherapy, amifostine, and PBSC support as in group 1. (Topotecan window closed to
accrual 9/10/2001) Patients undergo neuropsychological testing prior to radiotherapy
and chemotherapy and then at 1, 2, and 5 years.

Patients are followed at 1, 2, 4, 6, 9, 12, 15, 18, and 24 months and then every 6 months
for 3 years.

PROJECTED ACCRUAL: A total of 12-36 patients will be accrued for this study within 5 years.