Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme.

• - Progressive or recurrent disease previously treated with radiotherapy with or without chemotherapy.

• - Prior low-grade disease that progressed to high-grade after therapy 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/mm3.

• - Hemoglobin at least 8.5 g/dL.

Hepatic:

• - Bilirubin no greater than 1.5 mg/dL.

• - Transaminases no greater than 4 times upper limit of normal.

Renal:

• - Creatinine no greater than 1.7 mg/dL.

Other:

• - No other 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.

• - No serious concurrent infection.

• - No other medical illness that would preclude study.

• - Negative pregnancy test.

• - Not pregnant or nursing.

• - Fertile patients must use effective contraception.

PRIOR CONCURRENT THERAPY: Biologic therapy:

• - Not specified.

Chemotherapy:

• - See Disease Characteristics.

• - At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered.

• - No more than 1 prior chemotherapy regimen.

Endocrine therapy:

• - Must be on stable dose of steroids for at least 5 days.

Radiotherapy:

• - See Disease Characteristics.

• - At least 3 months since prior radiotherapy and recovered.

• - No more than 1 prior course of radiotherapy.

Surgery:

• - Not specified.

Other:

• - No other concurrent investigational agents.

- At least 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes

OBJECTIVES:

• - Determine the maximum tolerated dose of karenitecin in patients with recurrent malignant glioma who are receiving or not receiving anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.

• - Determine the pharmacokinetics of this drug in these patients.

• - Assess the preliminary evidence of therapeutic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to use of anticonvulsants known to be metabolized by the P450 hepatic enzyme complex (yes vs.#46;no). Patients receive karenitecin IV over 60 minutes on days 1-5. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of karenitecin according to the continual reassessment method until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose associated with a dose-limiting toxicity rate of 33%. Patients are followed every 2 months. PROJECTED ACCRUAL: Approximately 3-24 patients will be accrued for this study within 1 year.