A Prospective Study of Metronomic Oral Vinorelbine in Combination With Sorafenib in Advanced Non-small Cell Lung Cancer a) A Phase I Dose-finding Study of the Combination of Metronomic Oral Vinorelbine and Sorafenib b) Pharmacokinetics Profiling of the Combination of Metronomic Oral Vinorelbine and Sorafenib at MTD
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.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
to determine the optimal combination of metronomic oral vinorelbine with sorafenib to achieve anti-angiogenic and hence anti-tumour effect in patients with advanced NSCLC
every 1-2 monthly with DCE-MR and circulating endothelial cells apart from routine CT scans
Yes
Eng-Huat Tan, MD
Principal Investigator
National Cancer Centre, Singapore
Singapore: Health Sciences Authority
08-3-LUN
NCT00870532
June 2008
June 2013
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