Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors

BACKGROUND: * Histone deacetylase inhibitors (HDACi) have recently been shown to enhance the radiosensitivity of glioma cells both in vitro and in vivo. * Valproic acid has also recently been demonstrated to be a potent HDAC. * Valproic acid has a long clinical history in patients with and without brain tumors and is known to cross the blood-brain barrier. However, the use of valproic acid in combination with temozolomide and radiotherapy for patients with high-grade gliomas has never been tested. OBJECTIVES: -The primary measure of efficacy will be progression free survival and overall survival. ELIGIBILITY: * Patients greater than 18 years old * Diagnosis glioblastoma multiforme * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Patients who have not been previously treated with chemotherapy or radiation DESIGN: * This is a Phase II trial to determine the efficacy of valproic acid in combination with external beam radiation therapy and temozolomide in patients with high-grade gliomas. * Patients will be treated with external beam radiation therapy in a standard manner with temozolomide given daily during the radiation. The valproic acid will be administered daily beginning one week prior to the first day of irradiation and continuing until the completion of chemoradiation. * We anticipate that accrual to this trial of 41 patients will take approximately 1 year.