Conditions: Recurrent Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 94
Healthy volunteers: no

Brief summary:
This randomized phase II trial is studying carboplatin, paclitaxel, and vorinostat to see how well they work compared with carboplatin, paclitaxel, and a placebo in treating patients with stage III or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carboplatin and paclitaxel together with vorinostat is more effective than giving carboplatin and paclitaxel together with a placebo in treating non-small cell lung cancer

Detailed description:
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.

Arms:
arm 1: Patients receive oral vorinostat (SAHA) at 400 mg once daily on days 1-14 and paclitaxel IV 200 mg/m2 over 3 hours and carboplatin IV dosed to achieve an area under the concentration versus time curve of 6 mg/mLXmin over 30 minutes on day 3. arm 2: Patients receive an oral placebo once daily on days 1-14 and paclitaxel and carboplatin as in arm l.

Interventions: intervention 1: vorinostat intervention 2: paclitaxel intervention 3: carboplatin intervention 4: placebo intervention 5: laboratory biomarker analysis
Intervention descriptions: intervention 1: Given PO intervention 2: Given IV intervention 3: Given IV intervention 4: Given PO intervention 5: Correlative studies

Protocol document: