RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Irinotecan may make the tumor cells more sensitive to radiation therapy.

PURPOSE: This phase I/II trial is studying the side effects of irinotecan given together with radiation therapy followed by irinotecan and carmustine and to see how well it works in treating patients with newly-diagnosed glioblastoma multiforme.

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.

• 18 years and older
• Histologically confirmed newly diagnosed grade IV astrocytoma or gliosarcoma
• No oligodendrogliomas/oligoastrocytomas
• Study entry must occur within 8 weeks after surgery
• Performance status - ECOG 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 130,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT ≤ 2 times ULN
• Creatinine ≤ 0.5 mg/dL above ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No other concurrent malignant disease except superficial skin cancers
• No other major medical problems
• No prior chemotherapy
• No prior radiotherapy for any tumor