Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas
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
II. Determine the biologic activity of this drug by measuring proteasome 20S activity in
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of bortezomib defined as the dose level below that at which > 1 of 3-6 patients experience DLT
Graded using the CTC version 2.0.
New Approaches to Brain Tumor Therapy Consortium
United States: Food and Drug Administration
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