Phase III Randomized, Placebo Controlled, Trial of Docetaxel Versus Docetaxel Plus ZD1839 (Iressa, Gefitinib) in Performance Status 2 or Previously Treated Patients With Recurrent or Metastatic Head and Neck Cancer
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,
I. To determine the time to progression, response rate, and quality of life parameters 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 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, TGF-alpha, Ki-67, ERK, p-ERK, p70s6, p- p70s6 , and p27.
III. To evaluate the frequency of common polymorphisms of 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 FHNSI-10
OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients
are stratified according to treatment with prior chemotherapy (pretreated vs untreated),
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 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.
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Overall survival in poor prognosis SCCHN patients treated with docetaxel with or without ZD1839 (Iressa, gefitinib)
Will be performed using a one-sided log-rank test stratified on the 4 stratification factors.
Up to 5 years
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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