Clinical Trial Finder

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

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.#46;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.