talampanel in treating patients with recurrent high-grade glioma

Conditions: Brain and Central Nervous System Tumors

Summary: 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.

Eligibility criteria:
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

Keywords: recurrent adult brain tumor adult anaplastic astrocytoma adult glioblastoma adult anaplastic oligodendroglioma adult mixed glioma adult giant cell glioblastoma adult gliosarcoma adult brain stem glioma