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.

Condition	Treatment or Intervention	Phase
adult brain tumor	Drug: imatinib mesylate  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Austria
      Kaiser Franz Josef Hospital, Vienna,  A-1100,  Austria
Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre de Lutte Contre le Cancer, Georges-Francois Leclerc, Dijon,  21079,  France
      CRLCC Nantes - Atlantique, Nantes-Saint Herblain,  44805,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Italy
      Azienda Ospedaliera di Padova, Padova,  35100,  Italy
Netherlands
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland
United Kingdom, Scotland
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom

Study chairs or principal investigators

Eric Raymond, MD, PhD,  Institut Gustave Roussy   
Martin J. van Den Bent, MD,  Daniel Den Hoed Cancer Center at Erasmus Medical Center   

Study ID Numbers:  CDR0000069377; EORTC-16011; EORTC-26013
Record last reviewed:  October 2004
Last Updated:  October 13, 2004
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039364
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08