A Phase I/II Trial of Leflunomide in Combination With Vemurafenib in Patients With V600 Mutant Metastatic Melanoma
In this study we are looking for the highest dose of the study drug that can be administered
safely without severe or unmanageable side effects in participants that have metastatic
melanoma. For this reason, not everyone who participates in this research study will receive
the same dose of the study drug. The dose you get will depend on the number of participants
who have been enrolled in the study before you and how well they have tolerated their doses.
Both leflunomide and vemurafenib will be given as a pill to take by mouth. We will instruct
you to take leflunomide pills once a day and vemurafenib pills twice a day. We will give you
a study drug dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days (4
At the start of the study you will take leflunomide alone for the first 14 days of cycle 1.
For the first 3 days of cycle 1, you will receive a dose of leflunomide larger than you will
be receiving for the rest of the research study (loading dose). These first few larger doses
will introduce a certain amount of leflunomide into your body. The doses you receive after
Day 3 will be lower but will be used to maintain that level of leflunomide in your body.
Starting on Day 15, you will begin the twice-a-day Vemurafenib treatment while you continue
to take leflunomide once daily.
During all cycles you will have routine blood tests, a physical exam and you will be asked
questions about your general health and specific questions about any problems that you might
be having and any medications you may be taking. These procedures will be performed once
every cycle throughout the study.
If you have a skin lesion that can be surgically removed, the study doctor may ask you to
undergo additional skin punch biopsies as part of this research study. These samples will be
taken at three times throughout the study: before you begin the study treatment, after the
initial 2-week study treatment of leflunomide alone, and then 2 weeks after starting the
leflunomide and vemurafenib combination. We will assess your tumor by either CT scan or MRI
scan once every eight weeks while you are in this research study.
After you have completed participation in this study we would like to keep track of your
medical condition for the rest of your life. We would like to do this by calling you on the
telephone once every 4 weeks to see how you are doing. Keeping in touch with you and
checking your condition every year helps us to look at the long-term effects of the research
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I: Determine maximum tolerated dose of Vemurafenib + Leflunomide
To determine the maximum tolerated dose of vemurafenib plus leflunomide in patients with metastatic melanoma with V600 mutation with a requirement that fewer than one third of patients have dose-limiting toxicities. The goal of the study is to combine vemurafenib and leflunomide at their respective FDA approved doses and schedules.
United States: Institutional Review Board
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Brigham and Women's Hospital||Boston, Massachusetts 02115|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|