Talampanel in Treating Patients With Recurrent High-Grade Glioma
Talampanel in Treating Patients With Recurrent High-Grade Glioma
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