Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: imatinib mesylate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult pilocytic astrocytoma, recurrent adult brain tumor, adult meningioma, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult subependymoma, adult grade III meningioma, adult giant cell glioblastoma, adult gliosarcoma