Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma

Summary: 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: 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).

Eligibility: 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

Relevance to patient case: not relevant