RATIONALE: Drugs used in chemotherapy such as talampanel use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well talampanel works in treating patients with recurrent, progressive high-grade glioma.

OBJECTIVES:

• Determine the efficacy of talampanel, in terms of 6-month progression-free survival, in patients with recurrent high-grade gliomas.
• Determine, preliminarily, the toxic effects of this drug in these patients.
• Determine, preliminarily, the quality of life of patients treated with this drug.
• Determine the pharmacokinetics of this drug in patients who are and who are not receiving enzyme-inducing antiepileptic drugs.

OUTLINE: Patients are stratified according to type of glioma (anaplastic astrocytoma vs glioblastoma multiforme). Patients in each stratum are assigned to 1 of 3 treatment groups according to concurrent enzyme-inducing antiepileptic drug use (yes, no, or valproic acid).

Patients in each group receive different doses of oral talampanel 3 times daily on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 3 weeks during the first course, every 6 weeks before all subsequent courses, and then within 2 weeks of study completion.

Patients are followed within 2 weeks.

PROJECTED ACCRUAL: A total of 91 patients (50 with anaplastic astrocytoma and 41 with glioblastoma multiforme) will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed high-grade glioma, including any of the following:

  • Glioblastoma multiforme
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma

  • Malignant astrocytoma not otherwise specified

    • Patients with clinical and radiographic diagnosis of brain stem glioma are also eligible

• Evidence of tumor progression by MRI or CT scan

  • Scan must be performed while patient is on a stable steroid dose for at least 5 days
• Must have failed prior radiotherapy
• Residual disease after prior resection of recurrent or progressive tumor is allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3 (transfusion independent)
• Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic

• Bilirubin less than 2 times upper limit of normal (ULN)
• SGOT less than 2 times ULN
• No significant active hepatic disease

Renal

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min
• No significant active renal disease

Cardiac

• No significant active cardiac disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective methods of contraception during and for 2 months after study participation
• Able to swallow whole capsules
• No active infection requiring IV antibiotics
• No significant active psychiatric disease that would preclude use of the study drug
• No other significant uncontrolled medical illness that would preclude study participation
• No other active life-threatening malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 1 week since prior interferon or thalidomide
• No concurrent anticancer immunotherapy

Chemotherapy

• At least 2 weeks since prior vincristine
• At least 3 weeks since prior procarbazine
• At least 6 weeks since prior nitrosoureas
• No other concurrent anticancer chemotherapy

Endocrine therapy

• See Disease Characteristics
• At least 1 week since prior tamoxifen
• Concurrent steroids for the control of increased intracranial pressure allowed

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent anticancer radiotherapy

Surgery

• See Disease Characteristics
• Prior recent resection of recurrent or progressive disease allowed

Other

• Recovered from all prior therapy
• At least 1 week since prior noncytotoxic agents (e.g., isotretinoin), except for radiosensitizers
• At least 4 weeks since prior investigational agents
• At least 4 weeks since prior cytotoxic therapy
• No other concurrent investigational agents