Phase I/II Trial of Oxaliplatin as Neoadjuvant Treatment in Adults With Newly Diagnosed Glioblastoma Multiforme
I. Determine the maximum tolerated dose of oxaliplatin in patients with newly diagnosed
glioblastoma multiforme who are receiving or not receiving anticonvulsants known to be
metabolized by P450.
II. Determine the dose-limiting toxicity and safety profile of this drug in this patient
III. Assess the pharmacokinetics of this drug on this schedule and determine the effects of
P450-inducing anticonvulsants on the pharmacokinetics in these patients.
IV. Determine the radiographic response rate in patients treated with this drug.
V. Determine survival and drug toxicity in these patients.
OUTLINE: This is a phase I dose-escalation study of oxaliplatin followed by a phase II
study. Patients are stratified according to whether concurrent anticonvulsant drugs induce
P450 (yes vs modest/no or no drugs).
Phase I: Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14
days for a maximum of 6 courses in the absence of unacceptable toxicity or disease
Cohorts of 3-6 patients (per stratum) receive escalating doses of oxaliplatin until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity.
Phase II: Patients receive oxaliplatin as in phase I at the MTD determined in phase I.
Patients are followed at 1 month, every 2 months until disease progression, and then monthly
PROJECTED ACCRUAL: Approximately 24 patients (12 per stratum) will be accrued for the phase
I part of this study within 8-12 months. A total of 18-35 patients will be accrued for the
phase II part of this study within 5-12 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose (MTD) defined as the dose level at which 2 out of 6 or the dose level below that at which >= 2 of 3 or > 2 of 6 patients experience dose-limiting toxicity (DLT) assessed by Common Toxicity Criteria (CTC) version 2.0 (Phase I)
New Approaches to Brain Tumor Therapy Consortium
United States: Food and Drug Administration
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