Procarbazine in Treating Patients With Recurrent Brain Tumor

Study Overview
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Brief Summary
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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 procarbazine in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme following treatment with radiation therapy.

Detailed Description
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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 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.

Official Title
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A Phase I/II Study of Oral Procarbazine in the Treatment of Recurrent High Grade Astrocytomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: procarbazine hydrochloride


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: procarbazine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma