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.
Is the drug Vemurafenib a promising treatment for melanoma?Yes, Vemurafenib is a promising drug for treating melanoma, especially for patients with a specific mutation called BRAF V600E. It has been shown to improve survival rates and slow down the progression of the disease compared to other treatments.23456
What safety data is available for Vemurafenib and Metformin in melanoma treatment?Vemurafenib, approved by the FDA in 2011, has been shown to improve survival rates in patients with BRAF V600E mutation-positive melanoma. It has a favorable toxicity profile but can cause side effects, including secondary skin tumors. Safety data from trials indicate improved progression-free and overall survival. However, specific safety data for the combination of Vemurafenib and Metformin in melanoma treatment is not detailed in the provided research.12356
What data supports the idea that Vemurafenib + Metformin for Melanoma is an effective drug?The available research shows that vemurafenib, a drug used for treating melanoma with a specific mutation (BRAF V600E), has been effective on its own. It has improved survival rates and reduced the risk of death or disease progression significantly compared to another drug, dacarbazine. However, there is no specific data provided about the combination of vemurafenib with metformin for melanoma. The research does mention metformin being tested with other drugs, but not with vemurafenib. Therefore, while vemurafenib alone is effective, there is no direct evidence here about the combination with metformin.12367
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you have previously been treated with Vemurafenib or have a known hypersensitivity to Metformin, you cannot participate. It's best to discuss your current medications with the trial team.
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.
I can take care of myself and am up and about more than half of my waking hours.
Exclusion Criteria
I have not had radiotherapy for non-brain issues in the last 2 weeks or I have recovered from its side effects.
I have been treated with Vemurafenib before.
My melanoma got worse while I was taking Metformin.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Vemurafenib and MetforminExperimental Treatment2 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 nearbySelect from list below to view details:
James Graham Brown Cancer Center-University of LouisvilleLouisville, KY
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Who is running the clinical trial?
University of LouisvilleLead Sponsor
James Graham Brown Cancer CenterCollaborator
References
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.
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.
[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.
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.
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.
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.
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.