Phase I/II Trial of Temozolomide and Carboplatin in Recurrent Glioblastoma Multiforme
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of temozolomide and carboplatin in
patients with recurrent glioblastoma multiforme. II. Determine the acute and long-term toxic
effects of this regimen in these patients. III. Determine the pharmacokinetics of this
regimen in these patients. IV. Determine the potential of either a pharmacokinetic- or
pharmacodynamic-mediated drug interaction in patients treated with this regimen. V.
Determine the objective response rate in patients treated with the established MTD of this
regimen. VI. Determine time to tumor progression and survival in patients treated with this
OUTLINE: This is a dose-escalation study. Patients are stratified according to prior
nitrosourea-based chemotherapy (yes vs no). Patients receive carboplatin IV over 30 minutes
on day 1 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for a
maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with a persistent response may continue to receive temozolomide only for an
additional 6 courses. Cohorts of 3-6 patients receive escalating doses of carboplatin and
temozolomide 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, additional patients are accrued to receive carboplatin and
temozolomide at the recommended phase II dose.
PROJECTED ACCRUAL: A total of 13-70 patients (3-30 for phase I and 10-40 for phase II) will
be accrued for this study.
Primary Purpose: Treatment
Michael L. Gruber, MD
New York University School of Medicine
United States: Federal Government
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