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

Inclusion 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.