Leflunomide+Vemurafenib in V600 Mutant Met. Melanoma

• Status: Terminated
• Trial end date: 2014-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This research study was intended to be a Phase I/II clinical trial, but the trial was terminated before the phase 1 portion was completed. Phase I clinical trials test the safety of an investigational combination of drugs. Phase I studies also try to define the appropriate dose of the investigational drug combination to use for the Phase II portion of the study, which will enroll more participants and continue to study the effects of the drug and the safest dose. "Investigational" means that the combination of vemurafenib and leflunomide is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved this drug combination for your type of cancer.

Genes are a specific part of your cell materials which send code messages to determine what the investigators bodies look like, such as eye color, and instruct cells to control growth and development of the body. Researchers have found that a large number of melanoma cells have mutations in the BRAF gene. Normally, the BRAF gene helps to control how cells grow. Mutations in the BRAF gene may disrupt this control and allow cells in the skin to change into cancer cells, in which case, the cells keep dividing and growing out of control. Specifically, it has been shown that vemurafenib blocks the effects of these mutations in the BRAF gene, and, as a result, may help to prevent cancer growth. The FDA has approved vemurafenib for use in patients with BRAF mutation positive melanoma that is unable to be removed by surgery (unresectable) or that has spread (metastatic).

Leflunomide is in a class of medications called disease-modifying antirheumatic drugs (DMARDs). It is FDA approved for the treatment of rheumatoid arthritis and it is believed to decrease inflammation in that setting. However it is not approved for treatment of melanoma. The researchers of this study believe this agent may help prevent cancer growth as well as enhance the properties of drugs that target the BRAF gene (such as vemurafenib) based on recently published laboratory research, and would like to learn more about any effects this combination may have on your disease.

The main purposes of this study are to determine the highest dose of vemurafenib and leflunomide that can be given in combination without causing severe side effects, to see whether the combination of vemurafenib and leflunomide is safe in participants with BRAF mutant metastatic melanoma and to learn if the combination of vemurafenib and leflunomide shows any signs of effectively treating your disease.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: Leflunomide; Vemurafenib

Criteria

Inclusion Criteria:

• Histological or cytological confirmation of metastatic or unresectable melanoma

• Melanoma must be documented to contain a BRAF V600 mutation by a CLIA approved assay

• Measurable disease

• Less than or equal to 2 prior systemic treatment regimens for distant metastatic disease

Exclusion Criteria:

• Pregnant or breastfeeding

• Chemotherapy or radiation therapy within 4 weeks

• Prior therapy with a BRAF inhibitor or MEK inhibitor or leflunomide

• Receiving other study agents

• Known brain metastases that are symptomatic and require corticosteroids

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vemurafenib or leflunomide

• Uncontrolled intercurrent illness

• HIV-positive

• History of a different malignancy