Pemetrexed and LBH589 in Patients With Advanced Non-Small Cell Lung Cancer

Objectives 1. To determine the maximum tolerated dose of LBH589 given on a three times weekly schedule when combined with pemetrexed for the treatment of patients with advanced thoracic malignancies, except squamous cell carcinoma of the lung (phase I part). 2. To determine the overall response rate and non-progression rate (clinical benefit rate) and progression-free survival of the combination of LBH589 and pemetrexed in patients with previously-treated advanced NSCLC (phase II part). 3. To determine the pharmacodynamic effects of LBH589 and pemetrexed on levels of histone deacetylase (HDAC) 1 and 6 in peripheral blood mononuclear cells, as well as on levels of vascular endothelial growth factor (VEGF) levels in the blood. 4. To identify biomarkers in baseline, archival tumor tissue that may correlate with antitumor efficacy. Subject population Phase I: We will enroll patients treated with any number of prior regimen and all thoracic malignancies, except squamous cell carcinoma of the lung. Phase II: We will enroll patients with recurrent or progressive NSCLC who have received 1 prior chemotherapy regimen (1 additional regimen in the setting of initial curative treatment is allowed if completed \>1 year earlier). Treatment plan * Pemetrexed 500mg/m2 IV, day 1, every 21 days, on the first day of the week LBH589 is given. * LBH589 three-times-a-week (doses will be at least 2 days apart, e.g. Monday, Wednesday, Friday), until disease progression or intolerable toxicities LBH589 will start the week prior to the first pemetrexed cycle and pharmacodynamic (PD) studies will be performed (week -1) Study design and sample size: This is a phase I/II study. Phase I: 9-18 patients (estimated); Phase II: 17-41 patients (estimated).