Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors
Condition: High Grade Gliomas; Brain Tumors
MeSH terms: Glioma; Brain Neoplasms
Intervention: adjuvant therapy; Temozolomide; Valproic Acid; Radiation therapy
Intervention description: Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation.; Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.; External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Intervention MeSH terms: Temozolomide; Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Chemotherapy; Radiation; Brain Tumor; GBM; Radiosensitizer; Glioblastoma; Glioblastoma Multiforme

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.
    

Eligibility criteria:

        -  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.