Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00302159
First received: March 11, 2006
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

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.

Condition Intervention Phase
High Grade Gliomas
Brain Tumors
Procedure: adjuvant therapy
Drug: Temozolomide
Drug: Valporic Acid
Radiation: Radiation therapy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Progression-free survival. [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]

Enrollment: 35
Study Start Date: March 2006
Estimated Study Completion Date: June 2015
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: adjuvant therapy
    N/A
    Drug: Temozolomide
    N/A
    Drug: Valporic Acid
    N/A
    Radiation: Radiation therapy
    N/A
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
  • 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.
  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00302159

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-6056
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23284
Sponsors and Collaborators
Investigators
Principal Investigator: Kevin A Camphausen, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00302159     History of Changes
Obsolete Identifiers: NCT00313664
Other Study ID Numbers: 060112, 06-C-0112
Study First Received: March 11, 2006
Last Updated: November 26, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Chemotherapy
Radiation
Brain Tumor
GBM
Radiosensitizer
Glioblastoma
Glioblastoma Multiforme

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Valproic Acid
Temozolomide
Histone Deacetylase Inhibitors
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on April 17, 2014