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).

DISEASE CHARACTERISTICS:

• Histologically confirmed recurrent or unresectable malignant glioma

  • Glioblastoma multiforme (phase I only)
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
  • Malignant astrocytoma not otherwise specified
  • Gliosarcoma
  • Low-grade histology with subsequent diagnosis of malignant glioma allowed (phase I only) OR
• Histologically confirmed recurrent or unresectable benign or malignant meningioma (phase I only)
• No prior intracranial hemorrhage
• Failed prior radiotherapy

• Progressive or recurrent disease by MRI or CT scan and/or resection

  • PET or thallium scan, MR spectroscopy, or surgical documentation required in patients who have received prior interstitial brachytherapy or stereotactic radiosurgery
  • Stable dose of steroids for 5-7 days prior to MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• More than 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• SGOT less than 2 times ULN
• No significant hepatic disease

Renal:

• Creatinine less than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• No significant renal disease

Cardiovascular:

• No significant cardiac disease
• No deep venous or arterial thrombosis within the past 6 weeks

Pulmonary:

• No pulmonary embolism within the past 6 weeks

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for up to 6 months after study participation
• No other serious concurrent medical illness
• No serious active infection
• No concurrent disease that would obscure toxicity or alter drug metabolism
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior interferon or thalidomide and recovered
• No concurrent immunotherapy
• No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy:

• Recovered from prior chemotherapy
• At least 4 weeks since prior cytotoxic therapy
• At least 2 weeks since prior vincristine
• At least 6 weeks since prior nitrosoureas
• At least 4 weeks since prior temozolomide
• At least 3 weeks since prior procarbazine
• Prior polifeprosan 20 with carmustine implant (Gliadel wafer) allowed
• Prior radiosensitizers allowed
• No other concurrent chemotherapy

• Phase I only:

  • Prior chemotherapy required for anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic mixed oligoastrocytoma
  • Prior treatment for up to 3 relapses allowed

• Phase II only:

  • Prior chemotherapy not required
  • Prior treatment for up to 2 relapses allowed

Endocrine therapy:

• See Disease Characteristics
• At least 1 week since prior tamoxifen and recovered
• No concurrent anticancer hormonal therapy

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Recovered from prior surgical resection of recurrent or progressive disease

Other:

• At least 1 week since prior non-cytotoxic agents and recovered
• At least 1 week since prior tretinoin and recovered
• At least 2 weeks since prior drugs that affect hepatic metabolism
• No other concurrent investigational agents
• No concurrent warfarin