chemotherapy in treating patients with progressive or recurrent brain tumors

Conditions: Brain and Central Nervous System Tumors

Summary: 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.

Eligibility criteria:
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

Keywords: recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult giant cell glioblastoma adult gliosarcoma