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 procarbazine in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme following treatment with radiation therapy.
Detailed description
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.
Interventions
DRUGprocarbazine hydrochloride
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 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)
Countries
United States
Outcome results
None listed