Clinical trial NCT00302159
Conditions: High Grade Gliomas Brain Tumors
Keywords: Chemotherapy Radiation Brain Tumor GBM Radiosensitizer Glioblastoma Glioblastoma Multiforme
Sponsor: National Cancer Institute (NCI)
Start date: 2006-03-01; Completion date: 2014-11-01
Enrollment: 43 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
Interventions: intervention 1: adjuvant therapy intervention 2: Temozolomide intervention 3: Valproic Acid intervention 4: Radiation therapy
Intervention descriptions: intervention 1: None intervention 2: Orally 75mg/m\^2 first day of radiation until completion. Restart 4 weeks post radiation. intervention 3: Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. intervention 4: External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Protocol documents: