Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas
- Determine the maximum tolerated dose of imatinib mesylate in patients with recurrent
malignant glioma or meningioma.
- Determine the safety profile of this drug in these patients.
- Determine the pharmacokinetics of this drug, with or without concurrent enzyme-inducing
anti-epileptic drugs (EIAEDs), in these patients. (Stratum of patients currently taking
EIAEDs closed to accrual as of 05/15/2003 for phase I and phase II)
- Determine angiogenic activity in vivo using functional neuro-imaging studies and in
vitro with assays of serum angiogenic peptides.
- Determine the efficacy of this drug, in terms of 6-month progression-free survival and
objective tumor response, in these patients.
OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
concurrent enzyme-inducing anti-epileptic drug use (yes [stratum closed to accrual as of
05/15/2003 for phase I and phase II] vs no).
- Phase I (patients with glioma or meningioma) Patients in cohorts 1 and 2 receive oral
imatinib mesylate (STI571) once daily on days 1-28. Patients in cohorts 3-5 receive
oral STI571 twice daily on days 1 and 3-28 of the first course and on days 1-28 of
subsequent courses. Courses repeat every 4 weeks in the absence of disease progression
or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of STI571 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.
- Phase II (patients with glioma) (glioblastoma multiforme patients excluded as of
05/15/2003) Patients receive oral STI571 at the MTD determined in phase I, 1-2 times
daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression
or unacceptable toxicity.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study within 6
months and a total of 39 patients will be accrued for phase II of the study within 6-8
months. (Glioblastoma multiforme patients excluded from phase II as of 05/13/2003).
Primary Purpose: Treatment
Patrick Y. Wen, MD
Dana-Farber Cancer Institute
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|
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|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|
|Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390-9063|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|