Imatinib Mesylate in Treating Patients With Gliomas
Imatinib Mesylate in Treating Patients With Gliomas
RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and slow the growth
 of the tumor.

 PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients
 who have gliomas.
OBJECTIVES:

 -  Determine the therapeutic activity of imatinib mesylate (in terms of objective response
 and progression-free survival at 6 months) in patients with gliomas.

 -  Determine the safety of this drug in these patients.

 -  Determine the pharmacokinetics of this drug in these patients.

 OUTLINE: This is a multicenter study. Patients are stratified according to glioma
 (glioblastoma multiforme vs anaplastic oligodendroglioma or mixed oligoastrocytoma vs
 anaplastic astrocytoma or recurrent low-grade astrocytoma).

 Patients receive oral imatinib mesylate once or twice daily. Treatment repeats every 4 weeks
 for up to 9 courses in the absence of disease progression or unacceptable toxicity.

 Patients are followed every 2 months for 6 months and then every 3 months thereafter.

 PROJECTED ACCRUAL: A total of 77 patients (29 patients with glioblastoma multiforme, 24
 patients with anaplastic oligodendroglioma or mixed oligoastrocytoma, and 24 patients with
 anaplastic astrocytoma or recurrent low-grade astrocytoma) will be accrued for this study.
DISEASE CHARACTERISTICS:

 -  Histologically or cytologically confirmed glioblastoma multiforme

 -  Recurrent disease by CT scan or MRI

 -  No prior chemotherapy OR

 -  No more than 1 prior chemotherapy regimen in adjuvant setting or for recurrent
 disease OR

 -  Histologically or cytologically confirmed anaplastic oligodendroglioma, mixed
 oligoastrocytoma, anaplastic astrocytoma, or recurrent low-grade astrocytoma

 -  Failed prior radiotherapy

 -  No more than 1 prior chemotherapy regimen

 -  Failed adjuvant chemotherapy OR

 -  Failed first-line chemotherapy

 -  At least 1 bidimensionally measurable target lesion

 -  At least 2 cm on contrast-enhanced CT scan or MRI

 PATIENT CHARACTERISTICS:

 Age:

 -  18 and over

 Performance status:

 -  ECOG 0-2

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  Neutrophil count at least 2,000/mm^3

 -  Platelet count at least 100,000/mm^3

 Hepatic:

 -  Bilirubin no greater than 1.5 times upper limit of normal (ULN)

 -  AST and ALT no greater than 2.5 times ULN

 -  Alkaline phosphatase no greater than 2.5 times ULN

 Renal:

 -  Creatinine less than 1.7 mg/dL

 Cardiovascular:

 -  Cardiac function normal

 -  No ischemic heart disease within the past 6 months

 -  Normal 12-lead ECG

 Other:

 -  No other prior or concurrent malignancy except cone-biopsied carcinoma of the cervix
 or adequately treated basal cell or squamous cell skin cancer

 -  No unstable systemic disease

 -  No active uncontrolled infection

 -  No psychological, familial, sociological, or geographical condition that would
 preclude study compliance

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception during and for 3 months after study

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  No concurrent anticancer biologic agents

 -  No concurrent cytokines (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

 Chemotherapy:

 -  See Disease Characteristics

 -  At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea)

 -  No concurrent chemotherapy

 Endocrine therapy:

 -  Must be on stable or decreasing dose of corticosteroids for at least 2 weeks

 Radiotherapy:

 -  See Disease Characteristics

 -  At least 3 months since prior brain irradiation

 -  No prior high-dose radiotherapy (more than 65 Gy), stereotactic radiosurgery, or
 internal radiotherapy unless the recurrence is histologically confirmed

 -  No concurrent radiotherapy

 Surgery:

 -  Prior surgery for primary brain tumor within the past 3 months allowed provided one of
 the following conditions are present:

 -  Postoperative imaging within 72 hours after surgery shows a clearly limited
 target lesion of at least 2 cm

 -  Postoperative follow-up shows a progressive and measurable target lesion

 -  A second measurable target lesion is present outside the surgical area

 Other:

 -  No concurrent warfarin or other anticoagulants

 -  No other concurrent anticancer agents

 -  No other concurrent investigational agents