Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas

OBJECTIVES:

• 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.