Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically proven malignant glioma of one of the following types: - Anaplastic astrocytoma.

• - Anaplastic oligodendroglioma.

• - Glioblastoma multiforme.

• - Progressive or recurrent disease after radiotherapy with or without chemotherapy.

• - Measurable disease by serial MR or CT.

PATIENT CHARACTERISTICS: Age:

• - 18 and over.

Performance status:

• - Karnofsky 60-100% Life expectancy: - Greater than 2 months.

Hematopoietic:

• - Absolute neutrophil count at least 1500/mm^3.

• - Platelet count at least 100,000/mm^3.

Hepatic:

• - Bilirubin no greater than 1.5 mg/dL.

• - SGPT/SGOT no greater than 4 times upper limit of normal.

Renal:

• - Creatinine no greater than 1.7 mg/dL.

Other:

• - No serious concurrent infection.

• - No other illness that would preclude study.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - No prior malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix.

PRIOR CONCURRENT THERAPY: Biologic therapy:

• - No concurrent filgrastim (G-CSF) during the first course.

Chemotherapy:

• - See Disease Characteristics.

• - No more than 1 prior chemotherapy regimen.

• - At least 3 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas) - No more than 2 prior courses of carmustine or lomustine and no greater than 460 mg/m2 or 220 mg/m2, respectively.

• - No prior procarbazine.

Endocrine therapy:

• - Not specified.

Radiotherapy:

• - See Disease Characteristics.

• - At least 3 months since prior radiotherapy.

Surgery:

• - Prior surgery allowed.

Other:

• - Recovered from toxicity of prior therapy.

• - At least 10 days since prior anticonvulsants for patients in Arm II.

• - No concurrent investigational agents.

• - No concurrent ethanol, ephedrine, isoproterenol, epinephrine, tricyclic antidepressants, paragyliline, narcotic analgesics, antihistamines, phenothiazines, hypotensives, or barbiturates.

- At least 14 days since prior antidepressants (e.g., SSRI and/or MAO inhibitor) - Must avoid foods high in tyramine (i.e., dark beer, wine, yogurt, cheese, bananas)

OBJECTIVES:

• - Determine the maximum tolerated dose of oral procarbazine when administered to patients with recurrent glioma receiving or not receiving anticonvulsants metabolized by the P450 hepatic enzyme complex.

• - Determine the pharmacokinetics of oral procarbazine, including any effects of hepatic enzyme inducing drugs, in these patients.

• - Assess the response rate to procarbazine in these patients.

• - Evaluate this regimen in terms of overall survival and duration of disease free survival in these patients.

• - Evaluate the toxicity of this regimen in these patients.

OUTLINE: Phase I of this study is a dose escalation study. Patients are stratified according to concurrent use of anticonvulsant drugs that induce cytochrome P450 (yes vs.#46; no drugs or modest-induction drugs).

• - Phase I: Patients receive oral procarbazine once daily for 5 days.

Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of oral procarbazine until the maximum tolerated dose (MTD) is determined.

• - Phase II: Once the MTD is determined, patients receive procarbazine as in Phase I.

Patients are followed every 2 months until death. PROJECTED ACCRUAL: A total of 24-35 patients will be accrued for this study.