Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors
Condition: High Grade Gliomas; Brain Tumors
MeSH terms: Glioma; Brain Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

        -  Radiation therapy with temozolomide (an anti-cancer drug) is standard therapy for
           treating brain tumors called glioblastomas.

        -  The drug valproic acid, currently approved for treating seizures, has been shown in
           laboratory tests to increase the radiosensitivity of glioma cells.

      Objectives:

      -To determine the effectiveness of adding valproic acid to standard treatment with radiation
      therapy and temozolomide for treating glioblastoma.

      Eligibility:

      -Patients 18 years of age and older with glioblastoma multiforme who have not been previously
      treated with chemotherapy of radiation.

      Design:

        -  This Phase II trial will enroll 41 patients.

        -  Patients will receive radiation therapy to the brain once a day, Monday through Friday,
           for 6 1/2 weeks.

        -  Patients will take temozolomide once a day by mouth, Monday through Friday, during the
           period of radiation treatment. Starting 4 weeks after radiation therapy, patients will
           take temozolomide once a day for 5 days every 28 days for a total of six cycles.

        -  Patients will receive valproic acid by mouth twice a day beginning 1 week prior to the
           first day of radiation therapy and continuing until the completion of chemotherapy and
           radiation therapy.

        -  Patients will have follow-up visits 1 month after completing therapy, then every 3
           months for 2 years, and then every 6 months for 3 years. Follow-up includes a physical
           examination, blood tests and magnetic resonance imaging of the brain.
    

Detailed description: 
      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.
    

Intervention name(s): adjuvant therapy; Temozolomide; Valproic Acid; Radiation therapy
Intervention type(s): Procedure; Drug; Drug; Radiation
Intervention description(s): Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation.; Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.; External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Other intervention name(s): Temodar; Depakote
Intervention MeSH terms: Temozolomide; Valproic Acid
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chemotherapy; Radiation; Brain Tumor; GBM; Radiosensitizer; Glioblastoma; Glioblastoma Multiforme