Phase I-II Trial of CPT-11 and Temozolomide (Temodar) in Patients With Recurrent Malignant Glioma
- 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.
In phase II of the study, patients receive the same treatment as in phase I at the MTD.
Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months
for 1 year, every 6 months until progression, and then every 4 months for survival.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for phase I within 10 months and
48 patients will be accrued for phase II within 6-8 months.
Primary Purpose: Treatment
Wai-Kwan A. Yung, MD
M.D. Anderson Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|
|Jonsson Comprehensive Cancer Center, UCLA||Los Angeles, California 90095-1781|
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|
|Hillman Cancer Center at University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15236|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|