Chemotherapy in Treating Patients With Progressive or Recurrent Brain Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of irofulven in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme.

OBJECTIVES: Determine the maximum tolerated dose (MTD) of irofulven alone or combined with anticonvulsants known to be metabolized by cytochrome P450 in patients with progressive or recurrent high-grade anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme. Assess the pharmacokinetics of this drug on this schedule and determine the effects of P450-inducing anticonvulsants on the pharmacokinetics in these patients. Determine the response rate of patients treated with this drug administered at the MTD. Determine the duration of progression-free survival and overall survival of patients treated with this drug. Determine the toxic effects of this drug in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent use of anticonvulsant drugs that induce cytochrome P450 (yes vs no drugs or modest-induction drugs). Patients receive irofulven IV over 30 minutes on days 1-4 or 1-5 (depending on dose-escalation level). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients (per stratum) receive escalating doses of irofulven until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with irofulven at the recommended phase II dose. Patients are followed at 1 week and then every 2 months thereafter. PROJECTED ACCRUAL: Approximately 18 patients (9 per stratum) will be accrued for the phase I portion of the study. Approximately 17-35 patients will be accrued for the phase II portion of the study within 6-12 months.

recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma

DISEASE CHARACTERISTICS: Histologically proven malignant high-grade glioma that is progressive or recurrent after radiotherapy and/or chemotherapy Anaplastic astrocytoma Anaplastic oligodendroglioma Glioblastoma multiforme Prior low-grade glioma that has progressed to high-grade glioma after radiotherapy and/or chemotherapy allowed Measurable disease by MRI or CT scan PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL Transaminases no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No serious concurrent infection or medical illness that would preclude study therapy No other prior malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast Mini mental score at least 15 PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No more than 2 prior chemotherapy regimens At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered Endocrine therapy: Maintained on a stable corticosteroid regimen for at least 5 days before and during study Radiotherapy: See Disease Characteristics At least 3 months since prior radiotherapy and recovered Surgery: Recovered from prior surgery Other: No other concurrent investigational agents