Clinical Trial Finder

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

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.#46;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).