Imatinib Mesylate in Treating Patients With Gliomas

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Completed; Phase 2

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: imatinib mesylate

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00039364

EORTC-26013

EORTC-16011-26013

EORTC-16011

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 112 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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