Bortezomib in Treating Patients With Recurrent Glioma

OBJECTIVES: I. Determine the maximum tolerated dose of bortezomib with or without anticonvulsant drugs known to be metabolized by the P450 hepatic enzyme complex in patients with recurrent glioma. II. Determine the biologic activity of this drug by measuring proteasome 20S activity in these patients. III. Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsants, on biologic activity of this drug in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent anticonvulsant drug use (phenytoin, carbamazepine, phenobarbital, primidone, or felbamate vs gabapentin, lamotrigine, valproic acid, or no anticonvulsant drugs). Patients receive bortezomib IV over 3-5 seconds twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated with bortezomib at the MTD. Patients are followed every 2 months.