Project 465505

Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. Whereas, some patients can be cured with surgery alone, a significant number will need complimentary treatments since location such as optic pathway or brainstem precludes resection. Several clinical trials have focused on treatment of PLGG but with current approach using chemotherapy more than 50% will progress. Recently, specific inhibitors such as MEK inhibitors offer new alternatives for treatment of this tumor since it has been found that the majority of PLGG have an activation of the MAPK pathway. In a previous study, we demonstrated that we can achieved a reduction in tumor size in more than 70% of patients with PLGG with an excellent quality of life and a good tolerance when using MEK inhibitors in monotherapy. Giving the promising response rate, we are developing a new Canadian multicentric phase II clinical trial to evaluate the efficacy of mirdametinib combined with chemotherapy for newly diagnosed patient with PLGG. Mirdametinib is a drug designed to target the activation of the MAPK pathway and the vinblastine is the current standard chemotherapy for treatment of PLGG. Current data and experience suggest that this combination would be efficacious and well tolerated. We expect that it would allow us to achieve a rapid and more durable response. More importantly, this could translate in decreased morbidity and rapid improvement in symptoms. Our trial uses biological and genetic information to treat patients who are most likely to benefit from this drug combination. We will also analyze the quality of life and tolerance during treatment