Study of Combination of Metronomic Oral Vinorelbine and Sorafenib in Patients With Advanced Non-small Cell Lung Cancer

Phase I Dose-finding study: The patients will be divided into 3 cohorts (15 patients per cohort), each cohort receiving a fixed metronomic (thrice a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, and 120 mg/week respectively. Each patient within each cohort will receive a starting dose of sorafenib at 200 mg bid for 4 weeks. In the absence of dose-limiting toxicities, the dose of sorafenib will be escalated to 400 mg bid for another 4 weeks, 600 mg bid for 4 weeks and then finally 800 mg bid. We should arrive at 3 different MTDs from the 3 cohorts. Once the MTD has been determined for each cohort, we will recruit an additional 12 patients for each cohort and study the PK profile of both drugs. The 12 patients in each cohort will be sequentially alternated to group 1 or group 2 treatment schedules. Group 1 (N=6 patients in each cohort) will receive vinorelbine three times per week starting on Monday (Day 1) followed by Wednesday (Day 3) and Friday (Day 5). In the subsequent weeks vinorelbine will be given on the same working days (i.e. Monday, Wednesday and Friday). The first PK profile of vinorelbine (without concomitant sorafenib) will be determined on Day 15 under steady state conditions.