Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors
- Conditions
- High Grade GliomasBrain Tumors
- Interventions
- Registration Number
- NCT00302159
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Valproic Acid adjuvant therapy Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Valproic Acid Temozolomide Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Valproic Acid Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Valproic Acid Radiation therapy Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Overall Survival at 6, 12, and 24 Months 6, 12, and 24 months Percentage of participants who were alive at 6, 12, and 24 months.
Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months 6, 12, and 24 months Percentage of participants who were progression free by 6, 12, or 24 months. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.
Number of Participants With Best Response up to 63.8 months Best response recorded from the start of treatment until disease progression/recurrence. Complete response is complete resolution of all contrast enhancing tumor documented at initiation of treatment on protocol, with no appearance of new lesions. Partial response is a \>50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Minor response is a \>25%, but \<50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Stable disease is a change in tumor size less than MR but not demonstrating progressive disease. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol. Not evaluable means the participant cannot be evaluated (e.g., quality of scan).
Median Overall Survival up to 63.8 months Survival is the interval from the initiation of treatment on protocol to date of death.
Median Progression Free Survival. up to 51 months Progression free survival is the interval from initiation of treatment on protocol to symptomatic or radiographic progression. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events 6 years, 7 months and 27 days Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Trial Locations
- Locations (3)
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States