This phase I protocol will evaluate the safety and toxicity of escalating doses of oral phenylbutyrate in adult ambulatory patients with refractory or recurrent malignant glioma. Phenylbutyrate, a potential tumor differentiating agent and possible cytotoxic agent, has safely been given for many years to adults and children with urea cycle disorders where it acts as a sink for glutamine and thereby enhances nitrogen loss and prevents hyperammonemia. Phase I and II studies of phenylbutyrate and its metabolite phenylacetate (phenylacetate is formed by oxidation of phenylbutyrate) are ongoing in patients with a variety of malignancies. Both preclinical and early clinical data suggests that phenylacetate and phenylbutyrate are active against malignant gliomas. Preliminary results of a completed trial of intravenous phenylacetate in patients with malignant gliomas described radiographic responses and stable disease in a small number of patients. In this trial, the safety and toxicity of incrementally increasing doses of oral phenylbutyrate will be tested. OBJECTIVES: + To determine the maximum tolerated dose of sodium phenylbutyrate taken orally three times a day in patients with refractory CNS tumors until evidence of tumor progression. + To describe the pharmacokinetic parameters of oral phenylbutyrate and to escalate the dose of phenylbutyrate in an attempt to achieve plasma levels of 2-6 mmol/L while evaluating patient tolerability on the continuous oral exposure schedule. + To seek preliminary evidence of therapeutic activity of phenylbutyrate when administered on this schedule to patients with refractory CNS tumors. + To correlate any observed responses and toxicity with results of bioassaya and tissue sampling for phenylbutyrate activity.
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