A Phase I Study of Imatinib Mesylate in Combination With Temozolomide in Patients With Malignant Glioma
- Determine the maximum tolerated dose and dose-limiting toxicity, if attainable, of
imatinib mesylate in combination with temozolomide in patients with malignant glioma.
- Characterize the safety and tolerability of imatinib mesylate, including acute and
chronic toxicities, in these patients.
- Determine the effect of temozolomide on the pharmacokinetics (PK) of imatinib mesylate
at each dose level.
- Evaluate the impact of enzyme-inducing anti-epileptic drug (EIAED) coadministration on
the PK of imatinib mesylate using a population-based PK approach.
- Evaluate the antitumor activity of imatinib mesylate plus temozolomide.
OUTLINE: This is a dose-escalation study of imatinib mesylate. Patients are stratified
according to concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital,
carbamazepine, fosphenytoin, primidone, oxcarbazepine) (yes vs no).
Patients receive oral imatinib mesylate once or twice daily on days 1-8 and oral
temozolomide once daily on days 4-8. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of patients receive escalating doses of imatinib mesylate until the maximum
tolerated dose is determined.
On days 1 and 8 of course 1, blood is drawn for pharmacokinetic studies.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Primary Purpose: Treatment
Maximum tolerated dose
David A. Reardon, MD
Duke Cancer Institute
United States: Food and Drug Administration
|Duke Cancer Institute||Durham, North Carolina 27710|