Leflunomide+Vemurafenib in V600 Mutant Met. Melanoma

NCT01611675 | Terminated Phase 1 DMC

• 1 other identifier: 12-088
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Melanoma

Keywords

Metastatic; Unresectable; Clearly progressive; BRAF mutation

Outcome Measures

Primary Outcomes (2)

• 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.

  3 months

• Phase II: Assess Efficacy of Leflunomide + Vemurafenib

  To assess the efficacy (as measured by progression-free survival (PFS)) of patients with metastatic melanoma with V600 mutation treated with the combination of leflunomide and vemurafenib.

  2 years

Secondary Outcomes (4)

• Phase I: Assess Toxicities of Vemurafenib + Leflunomide

  2 years

• Phase II: Estimate Rates of Response using RECIST

  2 years

• Phase II: Impact of Leflunomide on Pharmacodynamic Endpoints

  2 years

• Phase II: Further Investigation of Safety of Vemurafenib + Leflunomide

  2 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Leflunomide + Vemurafenib

Drug: Vemurafenib; Drug: Leflunomide

Interventions

Vemurafenib DRUG

take orally, twice daily

Treatment Arm

Leflunomide DRUG

take orally, once daily

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

Vemurafenib; Leflunomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Keith Flaherty, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 19, 2012
• First Posted: June 5, 2012
• Study Start: July 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: April 6, 2017

Record last verified: 2017-04

Locations

US (3)