Vemurafenib + Metformin for Melanoma

Recruiting in Palo Alto (17 mi)

Overseen by Jason Chesney, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Louisville

Disqualifiers: Prior Vemurafenib, Metformin hypersensitivity, others

No Placebo Group

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to evaluate the safety of Vemurafenib in combination with Metformin in melanoma patients. The phase II part of the study will also evaluate the clinical activity of the combined regiment. Based on pre-clinical studies and a phase I trial, the investigators hypothesize that the combination of an FDA-approved non-toxic dose of oral Metformin with Vemurafenib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Vemurafenib + Metformin for melanoma?

Vemurafenib has been shown to improve survival rates in patients with melanoma that have a specific genetic mutation (BRAF V600E), with studies showing a significant reduction in the risk of death and disease progression. Metformin, while primarily used for diabetes, has shown potential anticancer effects when combined with other treatments in laboratory studies. ^{1 2 3 4 5}

Is the combination of Vemurafenib and Metformin safe for humans?

Vemurafenib, used for treating melanoma with a specific mutation, has been shown to improve survival rates but can have side effects, including secondary skin tumors. Metformin, commonly used for diabetes, is generally considered safe, but specific safety data for the combination of Vemurafenib and Metformin is not provided in the available research. ^{1 2 4 5 6}

What makes the drug Vemurafenib unique for treating melanoma?

Vemurafenib is unique because it specifically targets the BRAF V600E mutation in melanoma, improving survival rates compared to traditional chemotherapy. It was the first selective BRAF inhibitor approved for this purpose, offering a targeted approach with a favorable safety profile. ^{1 4 5 6 7}

Eligibility Criteria

This trial is for adults with BRAFV600E melanoma (Stage IIIC or IV) who can perform daily activities (ECOG PS 0-2) and have a life expectancy of at least 3 months. Participants must be able to use contraception, not be pregnant, and have adequate organ function. They cannot have had prior Vemurafenib treatment or known Metformin hypersensitivity.

Inclusion Criteria

My melanoma is BRAFV600E positive and is at stage IIIC or IV.

My blood, kidney, and liver tests meet the required levels.

I am 18 years old or older.

Exclusion Criteria

I do not have any uncontrolled infections or conditions that could affect the study.

I have not had radiotherapy for non-brain issues in the last 2 weeks or I have recovered from its side effects.

You are allergic to metformin or any of the ingredients in it.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Evaluation of the safety of Vemurafenib in combination with Metformin in patients with unresectable Stage IIIC and Stage IV melanoma

Approximately 6 months

Regular monitoring visits

Phase II Treatment

Evaluation of the clinical activity of the combined Vemurafenib/Metformin regimen

28-day cycles until progression or unacceptable toxicity

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 12 weeks (+/- 7 days) after last drug dose

Treatment Details

Interventions

• Metformin (Other)
• Vemurafenib (Kinase Inhibitor)

Trial Overview The study tests the safety and effectiveness of combining Vemurafenib with Metformin in treating melanoma. It aims to see if this combination improves response rates and survival with little toxicity based on earlier studies.

Participant Groups

Group I: Vemurafenib and Metformin Experimental Treatment 2 Interventions

Vemurafenib is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Zelboraf for:

• Unresectable or metastatic melanoma with BRAF V600E mutation
• Erdheim-Chester Disease (ECD) with BRAF V600 mutation

🇪🇺 Approved in European Union as Zelboraf for:

• Adults with BRAF V600E mutation positive unresectable or metastatic melanoma

🇨🇦 Approved in Canada as Zelboraf for:

• Unresectable or metastatic melanoma with BRAF V600E mutation

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

James Graham Brown Cancer Center-University of Louisville Louisville, KY

Who Is Running the Clinical Trial?

University of Louisville Lead Sponsor

James Graham Brown Cancer Center Collaborator

References

1. Poland pubmed.ncbi.nlm.nih.gov

The outcomes of Polish patients with advanced BRAF-positive melanoma treated with vemurafenib in a safety clinical trial. [2020] The BRAF inhibitor vemurafenib has improved progression-free survival and overall survival in patients with BRAFV600-mutation-positive metastatic melanoma. Here we present the results of an open-label safety study with vemurafenib in patients with metastatic melanoma enrolled in Polish oncological centres.

2. United States pubmed.ncbi.nlm.nih.gov

Improved survival with vemurafenib in melanoma with BRAF V600E mutation. [2022] Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation.

3. Greece pubmed.ncbi.nlm.nih.gov

Effect of Metformin in Combination With Trametinib and Paclitaxel on Cell Survival and Metastasis in Melanoma Cells. [2021] Despite clinical benefit from treatment with dabrafenib and trametinib in melanoma patients with BRAF mutations, half relapse within months and one-third are unresponsive to treatment. We evaluated the anticancer potential of metformin in combination with trametinib plus paclitaxel, against four melanoma cell lines.

4. England pubmed.ncbi.nlm.nih.gov

Vemurafenib. [2021] In August 2011 vemurafenib (Zelboraf; Daiichi Sankyo/Roche), an inhibitor of BRAF kinase, was approved by the US Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with the BRAF(V600E) mutation.

5. Hungary pubmed.ncbi.nlm.nih.gov

[Vemurafenib (Zelboraf) in the therapy of melanoma]. [2018] The incidence of malignant melanoma is continuously rising, but the therapy of advanced melanoma remains insufficient. Advances in the understanding of the immunological and genetical background resulted in the development of a new target therapeutic agent, vemurafenib (Zelboraf) accepted by the FDA in 2011 and by the EMA in 2012. Vemurafenib improved the overall and progression-free survival of untreated melanoma with the mutation BRAF V600E. In a phase III study vemurafenib was associated with a 63% reduction in the risk of deaths compared with dacarbazine and of 74% in the risk of either death or disease progression. Objective response was 48% in the vemurafenib and 5% in the dacarbazine arm. Vemurafenib has special side effects, surprisingly even secondary skin tumors. Additional research is needed to understand the mechanism of drug resistance and to find new targeted therapeutic agents and combinations.

6. England pubmed.ncbi.nlm.nih.gov

Vemurafenib for the treatment of BRAF mutant metastatic melanoma. [2022] Vemurafenib was the first selective BRAF inhibitor licensed in cancer. It is indicated for the treatment of patients affected by advanced melanoma with BRAF V600 mutation. It has shown successful results in terms of efficacy together with a favorable toxicity profile. Other compounds such as the BRAF inhibitor dabrafenib and the immunotherapeutic agent ipilimumab are also approved in the same group of patients. This article reviews the chemistry, pharmacokinetics, pharmacodynamics and clinical development of vemurafenib. Moreover, its efficacy and toxicity are compared with dabrafenib and ipilimumab. A number of trials with vemurafenib alone or in combination with other drugs are also analyzed. These trials will determine the role of vemurafenib in the treatment of BRAF mutant melanoma in forthcoming years.

7. United States pubmed.ncbi.nlm.nih.gov

Development and validation of a rapid and simple LC-MS/MS method for quantification of vemurafenib in human plasma: application to a human pharmacokinetic study. [2019] Vemurafenib (Zelboraf) is a new tyrosine kinase inhibitor that selectively targets activated BRAF V600E gene and is indicated for the treatment of advanced BRAF mutation-positive melanoma. We developed a simple method for vemurafenib quantification using liquid chromatography-tandem mass spectrometry. A stability study of vemurafenib in human plasma was also performed.