Vorinostat, Carboplatin, and Paclitaxel in Treating Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

PRIMARY OBJECTIVES: I. To compare the response rate associated with the combination of vorinostat, carboplatin, paclitaxel versus carboplatin, paclitaxel and placebo for patients with previously untreated, advanced NSCLC. SECONDARY OBJECTIVES: I. To determine the time to progression and overall survival for the two regimens. II. To assess the safety profile of the regimen of vorinostat, carboplatin and paclitaxel for patients with advanced NSCLC. III. To understand mechanistic aspects of drug effect by conducting correlative science studies on peripheral blood, archived tumor tissue, and paired biopsies in consenting patients. OUTLINE: This is a multicenter, randomized study. Patients are stratified according to gender and brain metastasis (present vs absent). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral vorinostat (SAHA) once daily on days 1-14 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 3. Arm II: Patients receive an oral placebo once daily on days 1-14 and paclitaxel and carboplatin as in arm l. In both arms, treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.