Phase I-II Trial of CPT-11 and Temozolomide (Temodar) in Patients With Recurrent Malignant Glioma

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan when administered with temozolomide in patients with recurrent malignant glioma.
• Determine the safety profile of this regimen in this patient population.
• Determine the efficacy of this treatment regimen as measured by 6-month progression-free survival and objective tumor response in these patients.
• Characterize the pharmacokinetics of this treatment regimen in these patients.
• Determine the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., phenytoin, phenobarbital, carbamazepine, or primidone) (yes vs no).

In phase I of the study, patients receive oral temozolomide on days 1-5 and irinotecan IV over 90 minutes on days 1 and 14. Treatment continues every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients concurrently on EIAEDs undergo dose escalation of irinotecan. Cohorts of 3 to 6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.