Troriluzole or Placebo Plus Ipi Plus Nivo in Mel Brain Mets

Melanoma Clinical Trial

Official title: A Blinded, Randomized Phase 2 Study of Troriluzole in Combination With Ipilimumab and Nivolumab in Patients With Melanoma Brain Metastases Previously Treated With Anti-PD-1 Therapy

Status Terminated

Clinical Trial Summary

The purpose of this research is to test the safety and effectiveness of the investigational combination of Troriluzole, ipilimumab, and nivolumab, and to learn whether this combination works in treating melanoma that has spread to the brain.

Clinical Trial Description

This is a multi-center, double-blind, randomized, phase II signal-detection trial with a non-randomized safety run-in to assess the efficacy and safety of adding troriluzole to ipilimumab/nivolumab induction and nivolumab maintenance in patients with melanoma that has metastasized to the brain. Measuring the shrinking or growth of melanoma in participants will allow researchers to learn about these study drugs and provide information on the safety and effectiveness of this combination in treating melanoma.

The U.S. Food and Drug Administration (FDA) has not approved Troriluzole as a treatment for any disease. The U.S. Food and Drug Administration (FDA) has approved nivolumab, ipilimumab, and the combination of these two drugs as treatment options for melanoma that has metastasized to the brain.

Ipilimumab and nivolumab are drugs that treat cancer by blocking certain molecules in the body. This blocking action prevents other molecules from binding to cells involved in the immune system. With these changes, the immune system is more likely to become active, and will react more intensely when activated. The immune system is able to destroy cancer cells and reduce the size of tumors, so activating the immune system is an important part of cancer treatment. Ipilimumab blocks a molecule called cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), which normally decreases the activation of the immune system by binding to T-Cells, which are important immune system cells that can attack cancer cells. Nivolumab blocks a molecule called programmed death receptor-1 (PD-1), which also normally decreases the activation of the immune system.

Troriluzole is a drug that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. The primary mode of action of Troriluzole is reducing synaptic levels of glutamate. This may change parts of the immune system in the brain, which is could improve treatment outcomes with anti-cancer drugs such as ipilimumab and nivolumab that can work in the brain. This study is testing Troriluzole's ability to increase the effectiveness of ipilimumab and nivolumab treatment in melanoma that has spread to the brain, as well as testing the safety of the combination of these three drugs.

Participation in this research is expected to last up to 4 years: 1 year of treatment and 3 years of follow up.

About 108 subjects will take part in this research. ;

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

• NCT number: NCT04899921
• Study type: Interventional
• Source: Dana-Farber Cancer Institute
• Status: Terminated
• Phase: Phase 2
• Start date: June 30, 2021
• Completion date: May 29, 2023