• Progression-free survival (PFS) as assessed by neuroimaging and clinical evaluations at 6 months [ Designated as safety issue: No ]
  

• Overall survival (OS) as assessed by neuroimaging and clinical evaluations at 12 months [ Designated as safety issue: No ]
  
• Response as assessed by neuroimaging and clinical evaluations [ Designated as safety issue: No ]
  
• Time to progression as assessed by neuroimaging and clinical evaluations [ Designated as safety issue: No ]
  
• PFS as assessed by neuroimaging and clinical evaluations at 12 and 24 months [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the maximum tolerated dose of imatinib mesylate in patients with recurrent oligodendroglioma or mixed oligoastrocytoma who are currently on enzyme-inducing anticonvulsant therapy. (Phase I)
• Determine the efficacy of imatinib mesylate, as measured by response, survival, and progression-free survival, in patients with recurrent oligodendroglioma or mixed oligoastrocytoma. (Phase II)
• Compare pilot data of patients who have undergone > 2 prior chemotherapy regimens for recurrent, progressive, or mixed oligodendroglioma with traditional patients with recurrent or mixed oligodendroglioma. (Phase II and pilot study)
• Determine the toxicity and safety of this drug in these patients. (Phases I, II, and pilot study)
• Correlate, preliminarily, 1p/19q alterations, alpha-PDFGR gene amplification, and levels of related downstream signaling elements in tumor tissue with clinical response in patients treated with this drug. (Phases I, II, and pilot study)

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II and a pilot study.

• Phase I: Patients receive oral imatinib mesylate twice daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate 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:

  • Group 1 (concurrent enzyme-inducing anticonvulsants [EIACs]): Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.
  • Group 2 (non EIACs): Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.

In both groups, treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

• Pilot study: Patients are stratified and assigned to treatment groups as in phase II. Patients receive oral imatinib as in phase II.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 93 patients will be accrued to this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed oligodendroglioma or mixed oligoastrocytoma

  • Grade 2-4
  • Recurrent disease
• Patients with mixed gliomas must have > 25% oligodendrogliomatous component

• Failed prior surgery, radiotherapy, and temozolomide or nitrosourea-based therapy

  • Progressive disease by MRI or CT scan
• Measurable or evaluable disease by MRI or CT scan
• More than 2 prior chemotherapy regimens for progressive or recurrent disease (pilot study only)
• Currently taking anticonvulsants which can induce cytochrome p450 (e.g., phenytoin, carbamazepine, barbituates, or primidone (Phase I only)
• No prior or concurrent significant intratumoral hemorrhage

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 3 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No myocardial infarction within the past 6 months
• No congestive heart failure requiring maintenance therapy for life-threatening ventricular arrhythmias
• No New York Heart Association class III or IV heart disease

Other

• No active uncontrolled infection
• No other severe concurrent disease that would preclude study or interfere significantly with interpreting potential drug-induced toxic effects
• No other active malignancy except nonmelanoma skin cancer
• No concurrent serious immunocompromised status unless related to concurrent steroids
• HIV-positive patients allowed
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 2 weeks since prior biologic noncytotoxic agents (e.g., thalidomide or interferon)
• No concurrent biologic therapy or immunotherapy for brain cancer

Chemotherapy

• See Disease Characteristics
• No prior interstitial chemotherapy, including carmustine wafers, unless separate lesion seen on MRI outside of prior treatment field
• At least 2 weeks since prior vincristine
• At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy for brain cancer

Endocrine therapy

• At least 2 weeks since prior tamoxifen
• Concurrent corticosteroids allowed if dose stable for at least 1 week prior to study entry
• No concurrent hormonal therapy for brain cancer

Radiotherapy

• See Disease Characteristics
• At least 12 weeks since prior radiotherapy
• No prior stereotactic radiosurgery or interstitial brachytherapy unless separate lesion seen on MRI outside of prior treatment field
• No concurrent radiotherapy for brain cancer

Surgery

• See Disease Characteristics
• At least 2 weeks since prior surgery for initial or progressive disease and recovered
• No concurrent surgery for brain cancer

Other

• At least 2 weeks since prior isotretinoin
• At least 4 weeks since prior investigational agents

• No concurrent therapeutic warfarin or heparin

  • Low-dose warfarin and heparin (1 mg daily) allowed
• No other concurrent investigational or noninvestigational therapy for brain cancer