Gefitinib and Radiation Therapy in Treating Patients With Glioblastoma Multiforme

PRIMARY OBJECTIVES:

I. To identify the maximum tolerated dose of ZD 1839 (gefitinib) when given concurrently with cranial radiotherapy.

II. To determine if ZD 1839, given orally on a daily basis starting at the time of conventional radiation therapy (RT), may improve the overall survival of adults with newly-diagnosed supratentorial glioblastoma multiforme, compared with historical controls, stratifying by epidermal growth factor receptor (EGFR) status.

III. To determine, in a multi-institutional setting, the feasibility and toxicity of prescribing ZD 1839.

SECONDARY OBJECTIVES:

I. Whether ZD 1839 also improves progression-free survival in these patients.

OUTLINE: This is a phase I, dose-escalation study of gefitinib followed by a phase II study.

Patients receive gefitinib orally (PO) once daily (QD) for 7 weeks. Beginning 1 week after initiation of gefitinib, patients undergo radiation therapy QD 5 days a week for 6 weeks. Treatment with gefitinib continues for up to 18 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 2 years, and annually thereafter.

Inclusion criteria

• Histopathologically confirmed glioblastoma multiforme (with areas of necrosis)
• Diagnosis must be made by surgical biopsy or excision
• The tumor must be supratentorial in location
• The patient must have recovered from the effects of surgery, post-operative infection, or other complications before study entry
• Radiotherapy must begin =< five weeks after surgery, and Iressa (gefitinib) must begin one week prior to radiotherapy
• Patients must have an estimated survival of at least 8 weeks
• Zubrod performance status of 0-1
• A diagnostic contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) scan must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; preoperative and postoperative scans must be the same type
• Patients diagnosed only by stereotactic biopsy do not require the postoperative scan
• Patients unable to undergo magnetic resonance (MR) imaging because of non-compatible devices can be enrolled, provided pre and postoperative CT scans are obtained and are of sufficient quality
• Hemoglobin >= 10 grams
• Absolute neutrophil count >= 1500 (ANC) per mm^3
• Platelets >= 100,000 per mm^3
• Blood urea nitrogen (BUN) =< 25 mg
• Creatinine =< 1.5 mg
• Bilirubin =< 2.0 mg
• Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) =< 2 x normal range
• Patients must consent to submission of their tissue/serum
• The patient must sign a study-specific informed consent prior to study entry; if the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member

Exclusion criteria

• Recurrent or multifocal malignant gliomas
• Metastases detected below the tentorium or beyond the cranial vault
• Major medical illnesses or psychiatric impairments which, in the investigator's opinion, will prevent administration or completion of protocol therapy
• Previous radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
• Active connective tissue disorders, such as lupus or scleroderma which, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity
• Previous malignancies, except for non-melanomatous skin cancers and carcinoma in situ of the uterine cervix or bladder, unless disease-free for >= 3 years
• Prior chemotherapy or radiosensitizers for cancers of the head and neck region
• Patients with known acquired immune deficiency (AIDS); patients with AIDS require complex therapeutic regimens; the pharmacokinetic interactions of these regimens with ZD 1839 are unknown and therefore, pose a safety risk related to excess toxicity or interference with anti-viral effectiveness
• Patients with known multiple sclerosis, as these patients may have decreased tolerance for radiation therapy to the brain
• Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug
• Patients treated on any other clinical protocols within 30 days prior to study entry or during participation in the study