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.

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