Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed malignant primary glioma.

• - Glioblastoma multiforme.

• - Anaplastic astrocytoma.

• - Anaplastic oligodendroglioma.

• - Anaplastic mixed oligoastrocytoma.

• - Malignant astrocytoma not otherwise specified.

• - Stable or progressive disease.

• - Progressive disease after interstitial brachytherapy or stereotactic radiosurgery must be confirmed by positron emission tomography or thallium scan, magnetic resonance spectroscopy, or surgical biopsy.

• - Prior treatment for no more than 3 prior relapses allowed.

PATIENT CHARACTERISTICS: Age:

• - 18 and over.

Performance status:

• - Karnofsky 60-100% Life expectancy: - More than 8 weeks.

Hematopoietic:

• - WBC greater than 3,000/mm^3.

• - Absolute neutrophil count greater than 1,500/mm^3.

• - Platelet count greater than 120,000/mm^3.

• - Hemoglobin greater than 10 g/dL (transfusion allowed) Hepatic: - Bilirubin less than 1.5 times upper limit of normal (ULN) - SGOT less than 1.5 times ULN.

Renal:

• - Creatinine less than 1.5 mg/dL OR.

• - Creatinine clearance greater than 60 mL/min.

Other:

• - Not pregnant.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - No active infection.

• - No other concurrent significant medical illness that would preclude study participation.

• - No significant gastrointestinal risk factors (e.g., active ulcerative colitis) within the past 6 months.

• - No other malignancy within the past 3 years except non-melanoma skin cancer or carcinoma in situ of the cervix.

PRIOR CONCURRENT THERAPY: Biologic therapy:

• - At least 1 week since prior interferon.

• - No concurrent filgrastim (G-CSF) during the first course of study therapy.

Chemotherapy:

• - At least 2 weeks since prior vincristine.

• - At least 3 weeks since prior procarbazine.

• - At least 6 weeks since prior nitrosoureas.

• - Prior or concurrent temozolomide allowed if there is no evidence of progression while receiving therapy.

Endocrine therapy:

• - At least 1 week since prior tamoxifen.

• - Must be on a stable dose of corticosteroids for at least 5 days.

Radiotherapy:

• - See Disease Characteristics.

• - At least 3 weeks since prior radiotherapy.

Surgery:

• - See Disease Characteristics.

• - At least 1 week since prior surgical resection.

Other:

• - Recovered from all prior therapy.

• - No prior gefitinib.

• - At least 1 week since prior non-cytotoxic agents except radiosensitizers.

• - At least 4 weeks since prior cytotoxic therapy.

• - At least 4 weeks since prior investigational agents.

• - At least 3 years since prior therapy for other malignancy.

• - Concurrent therapeutic agents allowed at stable dosage.

- Concurrent enzyme-inducing anti-epileptic drugs allowed if continued during study participation

OBJECTIVES:

• - Determine the maximum tolerated dose of gefitinib when given in combination with temozolomide in patients with malignant primary glioma.

• - Determine the toxic effects of this regimen in these patients.

• - Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gefitinib. Patients are stratified according to use of concurrent enzyme-inducing anti-epileptic drugs (yes vs.#46; no). Patients receive oral gefitinib once daily on days 1-35 and oral temozolomide once daily on days 8-12 for the first course only. For the second and subsequent courses, patients receive oral gefitinib once daily on days 1-28 and oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib 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. Patients are followed every 2 months for 1 year and then every 3-6 months thereafter. PROJECTED ACCRUAL: Approximately 3-42 patients will be accrued for this study within 1-14 months.