Overview

This trial is active, not recruiting.

Conditions high grade gliomas, brain tumors
Treatments adjuvant therapy, temozolomide, valproic acid, radiation therapy
Phase phase 2
Target HDAC
Sponsor National Cancer Institute (NCI)
Start date March 2006
End date June 2013
Trial size 43 participants
Trial identifier NCT00302159, 06-C-0112, 060112, NCT00313664

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
adjuvant therapy
N/A
temozolomide Temodar
Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation.
valproic acid Depakote
Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
radiation therapy
External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Primary Outcomes

Measure
Median Progression Free Survival.
time frame: up to 51 months
Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months
time frame: 6, 12, and 24 months
Number of Participants With Best Response
time frame: up to 63.8 months
Median Overall Survival
time frame: up to 63.8 months
Percentage of Participants With Overall Survival at 6, 12, and 24 Months
time frame: 6, 12, and 24 months

Secondary Outcomes

Measure
Number of Participants With Adverse Events
time frame: 6 years, 7 months and 27 days

Eligibility Criteria

Male or female participants from 18 years up to 90 years old.

- INCLUSION CRITERIA: Histological diagnosis: Pathologically confirmed glioblastoma multiforme. Histologic diagnosis of glioblastoma multiforme (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 Eastern Cooperative Oncology Group (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 Radiation Oncology Branch (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 serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (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.

Additional Information

Official 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: Multi-Institutional Trial
Principal investigator Kevin A Camphausen, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by National Institutes of Health Clinical Center (CC).