A Phase III Prospective Randomized, Double-Blind, Placebo-Controlled Trial of the Epidermal Growth Factor Receptor Antagonist, ZD1839 (Iressa) in Completely Resected Primary Stage IB, II and IIIA Non-Small Cell Lung Cancer
- Compare the overall survival of patients with completely resected primary stage IB, II,
or IIIA non-small cell lung cancer treated with gefitinib vs placebo.
- Compare the disease-free survival of patients treated with these regimens.
- Determine the prognostic significance of epidermal growth factor receptor expression,
phosphorylation, and mutations in the primary tumor in predicting relative impact of
gefitinib on survival of these patients.
- Establish a comprehensive tumor bank linked to a clinical database for further study of
molecular markers in patients treated with these regimens.
- Determine the toxicity of gefitinib in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to disease stage (IB vs II vs IIIA), histological subtype (squamous
cell vs others), postoperative radiotherapy (yes vs no), prior adjuvant platinum-based
chemotherapy (yes vs no), and gender. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral gefitinib daily, unless otherwise directed by the
- Arm II: Patients receive oral placebo daily, unless otherwise directed by the
Treatment in both arms continues for up to 2 years in the absence of disease progression or
Patients are followed at 1 month, 3 months, and every 3 months for 30 months after
randomization, then every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 1,242 patients (621 per treatment arm) will be accrued for
this study within 3.5 years.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
The 3-year survival for the 60% of patients with stage IB and II together is about 63% for those who did not receive post-operative chemotherapy, and is 67% for those who had received post-operative chemotherapy. Assuming 75% of patients may receive post-operative chemotherapy, the corresponding median survival for this subgroup of patients is about 64 months (5.3 years)
approximately 6 years
Glenwood D. Goss, MD, BCh, FCP, FRCPC
Ottawa Regional Cancer Centre
United States: Food and Drug Administration