Trial Information

Pilot And Phase II Trial Of Irinotecan And Radiation Followed By Irinotecan And BCNU In Glioblastoma Multiforme Patients

OBJECTIVES:

- Determine the safety of adjuvant irinotecan when administered concurrently with
radiotherapy in patients with newly diagnosed glioblastoma multiforme.

- Determine survival of patients treated with this regimen followed by irinotecan and
carmustine.

- Assess the toxic effects of this regimen in these patients.

- Determine whether the dose of irinotecan chosen produces radiosensitizing plasma
concentrations of SN-38 in these patients.

- Assess individual variation in responses (toxicity and/or activity), pharmacokinetic
parameters, and/or biological correlates due to genetic differences in enzymes involved
in transport, metabolism, and/or mechanism of action of irinotecan in these patients
treated with this regimen.

OUTLINE: This is a pilot, dose-escalation study of irinotecan. Patients are stratified
according to receipt of concurrent enzyme-inducing anticonvulsants (EIACs) (yes vs no).

- Phase I (closed to accrual as of 3/5/2005): Patients receive carmustine IV over 2 hours
on day 1 of courses 2-5 and irinotecan IV over 90 minutes (beginning immediately after
carmustine infusion) on days 1, 8, 22, and 29 of courses 1-5. Patients also undergo
radiotherapy 5 days a week for 6 weeks concurrently with course 1 only. Treatment
repeats every 6 weeks for 5 courses in the absence of unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of irinotecan until the recommended dose for
phase II is determined. The recommended dose for phase II is defined as the dose at which no
more than 2 of 6 patients experience dose-limiting toxicity.

- Phase II (patients receiving concurrent EIACs or non-EIACs open to accrual as of
3/5/2005): Patients receive irinotecan at the recommended dose, carmustine, and cranial
irradiation as in phase I.

Patients with disease progression are followed every 3 months for 5 years and then annually
for up to 10 years.

Patients taken off study for reasons other than disease progression are followed every 3
months for 1 year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 12-48 patients (6-24 per stratum) will be accrued for phase I
within 2-4 months (phase I closed to accrual as of 3/5/2005). A total of 93 patients will be
accrued for phase II (open to accrual for patients receiving concurrent enzyme-inducing
anticonvulsants [EIACs] or non-EIACs as of 3/5/2005).