NCT00870532

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

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: National Cancer Centre, Singapore · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

Targeting the blood supply of cancer, called anti-angiogenesis is a new but proven treatment strategy. There are two ways of achieving this effect. The first way to specifically target the molecular pathways that promote new blood vessel formation in cancer. An example of such an agent is sorafenib, which is an oral agent and which is already in use worldwide for the treatment of kidney and liver cancers. The second way is to target the cells lining the blood vessels by using low dose of chemotherapy agents administered at frequent intervals. This strategy is called metronomic chemotherapy. It is possible that combining agents like sorafenib and metronomic chemotherapy may further enhance anti-cancer effects. This study aims to determine the optimal way of combining oral vinorelbine in metronomic doses and sorafenib. Oral vinorelbine is a chemotherapy agent that is already approved for use in cancer treatment such as lung cancer. By combining both oral anti-cancer agents to optimize their anti-angiogenic effects in this study, the potential benefit to the patients can be tremendous and far-reaching. Special radiologic imagings and blood tests will be incorporated into this study to help further the understanding of the anti-angiogenic processes of both agents.

Detailed description

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.

Conditions

• Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	oral vinorelbine	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. We should arrive at 3 different MTDs from the 3 cohorts.
DRUG	sorafenib	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.

Timeline

• Start date: 2008-06-01
• Primary completion: 2013-08-01
• Completion: 2013-09-01
• First posted: 2009-03-27
• Last updated: 2013-11-04

Locations

1 site across 1 country: Singapore