Brain and Central Nervous System Tumors
Conditions
Keywords
recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma
Brief 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.
Detailed description
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.
Interventions
DRUGirofulven
Sponsors
National Cancer Institute (NCI)
New Approaches to Brain Tumor Therapy Consortium
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed