Protocol Number: 06-C-0112

Title:

A Phase II Clinical Trial of the Histone Deacetylase Inhibitor Valproic Acid in Combination with Temodar and Radiation Therapy in Patients with High Grade Gliomas

Number:

06-C-0112

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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Histological diagnosis:

Pathologically confirmed glioblastoma multiforme.

Histologic diagnosis of GBM will have been established by biopsy or resection no more than 6 weeks prior to enrollment.

The patient is a candidate for definitive external beam radiotherapy.

Patients must be older than 18 years with a life expectancy greater than 8 weeks.

Patients should have an ECOG performance status of 0, 1, or 2.

Patients must have a primary medical oncologist in the community who is willing to collaborate with the ROB staff in the clinical management of the patient, specifically in the prescription of Temozolomide and toxicity monitoring in the adjuvant phase.

Laboratory functions:

Adequate bone marrow function defined as a peripheral absolute granulocyte count of greater than 1500/mm(3), hemoglobin greater than 10gm/dL, and platelet count greater than 100,000/mm(3).

Adequate liver function, defined as bilirubin and SGOT/SGPT less than 2 x the upper limit of normal.

Serum creatinine less than 1.5 mg/dl.

Serum albumin greater than 0.75 x normal.

All patients or their legal guardian must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study BEFORE any of the protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility).

Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

EXCLUSION CRITERIA

Prior therapy:

Patients who have previously received valproic acid.

Patients who have previously received radiation therapy to the brain.

Patients who have received chemotherapy for the treatment of their high grade glioma or who are currently receiving other investigational chemotherapeutic agents.

Patients with a known history of disorders of urea metabolism.

Concurrent therapy:

The concurrent use of sulfamethoxazole, salicylates or naproxen is not allowed.

Patients with a history of or concurrent second malignancy other than non-melanoma skin cancer or cervical cancer less than 3 years since GBM diagnosis.

Pregnant or breast-feeding females are excluded because of the potential mutagenic effects on a developing fetus or newborn.

Clinically significant unrelated systemic illness which in the judgement of the Principal or Associate Investigator would compromise the patient's ability to tolerate this therapy or are likely to interfere with the study procedures or results, including but not limited to Insulin dependent diabetes.

Special Instructions:

Currently Not Provided

Keywords:

Chemotherapy

Radiation

Brain Tumor

GBM

Radiosensitizer

Recruitment Keyword(s):

Brain Tumor

Glioblastoma Multiforme

GBM

Condition(s):

High Grade Gliomas

Brain Tumors

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Procedure/Surgery: External beam radiation therapy

Drug: Temozolomide

Drug: Valporic Acid

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

The conditional probability of survival of patients with primary malignant brain tumors: surveillance, epidemiology, and end results (SEER) data. Cancer. 1999 Jan 15;85(2):485-91.

Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group.Cancer. 1981 Feb 15;47(4):649-52.

Radiosurgery as part of the initial management of patients with malignant gliomas. J Clin Oncol. 1992 Sep;10(9):1379-85.

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