Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Meningioma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and may be an
      effective treatment for recurrent glioma and meningioma.

      PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate in treating
      patients who have progressive, recurrent, or unresectable malignant glioma or meningioma.
    

Detailed description: 
      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.

        -  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).
    

Intervention name(s): imatinib mesylate
Intervention type(s): Drug
Intervention MeSH terms: Imatinib Mesylate
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: recurrent adult brain tumor; adult meningioma; adult glioblastoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult mixed glioma; adult pilocytic astrocytoma; adult subependymoma; adult grade III meningioma; adult giant cell glioblastoma; adult gliosarcoma