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Minnesota Cancer Clinical Trials Network Funds Community Site Award for Colchicine Therapy for BRAFi/MEKi-Associated Pyrexia 

The Minnesota Cancer Clinical Trials Network (MNCCTN) is happy to announce the funding of a third study as part of the network’s inaugural grant program. The program, announced in January 2021, was intended to encourage the development of trials for the MNCCTN and broaden the depth and reach of clinical trials offered to cancer patients in Minnesota. The projects will each receive up to $125,000 for the funding cycle. Awardees will work in partnership with the MNCCTN HUB team on development and implementation of their studies over the next year.

The third study was awarded in the Community Site A category. Proposed trials in this category were required to come from one of MNCCTN’s five health care community partners. Studies in this category were required to open at all MNCCTN sites across Greater Minnesota. This category’s recipient is Principal Investigator Jesus Vera Aguilera, MD, from MNCCTN’s partner Essentia Health. Co- investigators for the study include Bret Friday, MD, PhD, also from Essentia Health; Jonas Paludo, MD, Mayo Clinic; and Svetomir N Markovic, MD, PhD, Mayo Clnic. Dr. Vera Aguilera’s study is titled, “Colchicine for the Management of BRAF/MEK Inhibitor Associated Pyrexia.” 

BRAF/MEK inhibitors (BRAFi/MEKi), a combination of drugs to prevent tumor growth due to cell mutations in the BRAF gene, lead to improved progression free survival and overall survival. However, this drug combination can have side effects, limiting their use. The most common side effect among all tumor types is pyrexia, or fever. If a patient has a fever, this can often lead to treatment interruption or discontinuation.

The cause of pyrexia in patients taking BRAFi/MEKi is not well understood. One potential cause may be hyperactivation of the MAPK pathway, a chain of proteins in cells that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Hyperactivation of this pathway is also seen in familial Mediterranean fever (FMF), a rare condition with fever episodes and rashes. FMF can be successfully treated with colchicine-based therapy.

In 2019, Dr. Vera Aguilera and his team tested colchicine for the treatment of BRAFi/MEKi-associated pyrexia in five patients with metastatic melanoma, and it was successful. In this new MNCCTN-funded study, patients with BRAF V600E mutations in which BRAFi/MEKi are approved for treatment by NCCN guidelines will be randomized to receive either colchine or a placebo. Participants will undergo five blood draws over eight weeks to measure cytokine levels. If successful, the study will demonstrate that colchicine reduces fever frequency and intensity for patients with BRAFi/MEKi-associated pyrexia. 

This study is especially relevant to MNCCTN because BRAFi/MEKi are most used for patients with advanced malignant melanoma. Minnesota has the third highest incidence rate of melanoma in the United States and is among a handful of states that have experienced an increase in both melanoma incidence and death rates over the past decade. MNCCTN, with access to patients statewide at 22 sites, is uniquely positioned to successfully execute this project.

This award and study are also unique and significant for MNCCTN because it funds a study developed directly at MNCCTN community sites by local clinicians and researchers, rather than at an academic center like most other clinical trials. This ensures that the MNCCTN grant program not only expands access to those enrolling onto clinical trials but also those conducting clinical trials. Members of the community also have a unique insight into the populations their health centers serve and what studies may best fit their needs. MNCCTN looks forward to continuing to support and assist community researchers with the experience and expertise to bring their ideas to fruition.