Mirdametinib + Vinblastine for Brain Tumor

(MIRV Trial)

This trial tests a new treatment combination for a specific type of brain tumor called PLGG, which affects the MAPK pathway—a chain of proteins in cells that controls cell functions. The study will determine if the combination of the oral drug mirdametinib and the chemotherapy drug vinblastine is safe and effective. It includes participants with PLGG who have certain genetic changes, such as the NF1 mutation or KIAA1549-BRAF fusion, but not the BRAF V600E mutation. Participants must have been diagnosed with PLGG, possess specific genetic markers, and must not have undergone previous treatments like radiotherapy. The trial aims to find the best dose and monitor the treatment's effectiveness over time. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving other investigational agents or have had previous systemic or radiotherapy treatment.

Research shows that combining mirdametinib and vinblastine may help treat certain brain tumors. Previous studies indicate that this treatment is generally well-tolerated, though it can have side effects like most medications. Common side effects include tiredness, nausea, and low blood cell counts, which can increase infection risk. More serious side effects are rare but possible.

Mirdametinib is unique because it targets a specific pathway involved in cell growth called the MAPK/ERK pathway, which is often overactive in certain brain tumors. Unlike traditional chemotherapy drugs that can affect both healthy and cancerous cells, mirdametinib is designed to more selectively inhibit tumor growth, potentially leading to fewer side effects. Researchers are excited about this treatment because it offers a new mechanism for tackling brain tumors, especially in cases where other treatments might not be effective. Additionally, the combination with vinblastine might enhance its effectiveness, providing a promising option for patients with limited alternatives.

In this trial, participants will receive a combination of mirdametinib and vinblastine to treat pediatric low-grade glioma (PLGG) involving the MAPK pathway. Research has shown that this combination may be promising, as studies have found it to be generally well-tolerated by patients, with some experiencing a reduction in tumor size. Mirdametinib blocks certain pathways that help cancer cells grow, while vinblastine, a chemotherapy drug, stops cancer cells from dividing. Previous patients using similar targeted treatments demonstrated a 25% response rate, suggesting that mirdametinib plus vinblastine could be an effective treatment option for PLGG.¹²³⁴⁶