A Phase II Trial of Gemcitabine, Carboplatin and PS-341 (NSC-681239) in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

PRIMARY OBJECTIVES: I. To assess overall survival in chemo-naϊve patients with advanced non-small cell lung cancer (NSCLC) treated with combination of gemcitabine, carboplatin and PS-341. SECONDARY OBJECTIVES: I. To assess response rate (confirmed plus unconfirmed, complete plus partial), in the subset of patients with measurable disease, progression-free survival and quantitative toxicities in this group of patients treated with this regimen. II. To investigate in an exploratory manner, the association of levels of hypoxia-induced secreted proteins and tumor DNA in plasma levels of apoptosis-associated proteins in tumor tissue, and the changes in the levels of PS-341 modulated proteins in peripheral white blood cells with patient response and survival. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may continue to receive bortezomib alone on the above schedule for up to 1 year at the discretion of the treating physician. Patients are followed every 6 months for up to 3 years after registration. PROJECTED ACCRUAL: A total of 99 patients will be accrued for this study within 5 months.