Phase III Trial Of Docetaxel Versus Docetaxel Plus ZD1839 In Head And Neck Cancer

PRIMARY OBJECTIVES: I. To determine the survival of poor prognosis patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with docetaxel with or without ZD1839 (Iressa, gefitinib). SECONDARY OBJECTIVES: I. To determine the time to progression and response rate in poor prognosis patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with docetaxel with or without ZD1839 (Iressa, gefitinib). II. To correlate the expression and activation status of the epidermal growth factor receptor (EGFR) signaling pathway with clinical outcome in the above patient population. The following specific biomarkers will be measured by immunohistochemistry on paraffin-embedded tumor tissue: EGFR, p-EGFR, AKT, p-AKT, Transforming growth factor (TGF)-alpha, Ki-67, extracellular-signal-regulated kinase (ERK), p-ERK, p70s6, p- p70s6 , and p27. III. To evaluate the frequency of common polymorphisms of Cytochrome P450 3A (CYP3A) and EGFR in this study population and the impact of these polymorphisms on survival, time to progression, response rate, and toxicities. IV. To analyze docetaxel and ZD1839 (Iressa, gefitinib) pharmacokinetics and to correlate polymorphisms with pharmacokinetic variability, response, toxicity, and other endpoints. V. To evaluate disease-related symptoms and overall quality of life among patients receiving docetaxel only to those receiving docetaxel and ZD1839 (Iressa, gefitinib). VI. To evaluate whether additional clinical benefit associated with ZD1839 (Iressa, gefitinib) can be detected as an improvement in patient-reported symptoms on the FACT Head and Neck Symptom Index (FHNSI)-10 and GP5. OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to treatment with prior chemotherapy (pretreated vs untreated), Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), weight loss within the past 6 months (\< 5% vs ≥ 5%), and prior cetuximab treatment (yes or no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive docetaxel intravenously (IV) over 30-60 minutes on days 1, 8, and 15 and oral placebo once daily on days 1-28. Arm II: Patients receive docetaxel as in arm I and oral gefitinib once daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in arm I who have disease progression may receive single-agent oral gefitinib once daily until further disease progression (which is called step 2 in the study). Quality of life is assessed at baseline, on days 15 and 28 of course 1, on day 28 of all subsequent courses, and at 2-4 weeks after completion of study treatment. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 330 patients (165 per treatment arm) will be accrued for this study within 31.5 months.