Phase III Randomized, Double-Blind Study of CAI and Placebo in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

PRIMARY OBJECTIVES: I. To determine whether oral administration of the carboxyaminoimidazole (CAI) is more effective than placebo in prolonging the overall survival in patients with non-small cell lung cancer stage III or stage IV non-small cell lung cancer who have been stable or had tumor regression following chemotherapy. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of oral CAI following chemotherapy. II. To determine whether CAI prolongs time-to-disease progression relative to a placebo. III. To evaluate whether a substantive effect in quality of life (QOL) can be detected between the CAI and placebo groups using the FACT-L and the UNISCALE. IV. To document the response rate to CAI in patients with measurable or evaluable disease. TERTIARY OBJECTIVES: I. To evaluate genotypes at GSH-related loci as predictors of overall survival. OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to timing of first-line therapy (prior to registration vs after registration), disease stage (IIIA vs IIIB vs IV), therapy components (chemotherapy and thoracic radiotherapy vs chemotherapy only), ECOG performance status (0 vs 1 vs 2) and participating center. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral carboxyamidotriazole daily. ARM II: Patients receive oral placebo daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and then monthly during study. Patients are followed every 3 months for 5 years.