New Treatments Using Leflunomide or MEK Inhibitor with Hydroxychloroquine for Advanced Tumors With RAS Gene Mutations

What this Trial Is About

Mutations in the RAS gene, including KRAS, NRAS, and HRAS, are common causes of many tumors. Researchers are evaluating the potential of drugs originally approved for other conditions to target different parts of the RAS pathway. This trial focuses on patients with refractory malignancies who have failed standard treatments and have documented RAS mutations, aiming to explore new therapeutic options that may improve outcomes. The study compares two experimental treatments leflunomide, taken as a loading dose of 100 mg daily for 3 days followed by 20 mg daily, and a combination therapy consisting of a MEK inhibitor options include trametinib, cobimetinib, or binimetinib plus hydroxychloroquine, with or without bevacizumab. Bevacizumab is included due to its potential benefit in colorectal cancer with KRAS mutations. There is also a historical control group receiving standard therapy. Each treatment cycle lasts 28 days, and responses are assessed after two cycles. Participants will have their cancer status monitored through objective response rates measured at the end of two treatment cycles. Quality of life, progression-free survival, and overall survival up to three years will also be evaluated. The trial requires informed consent and regular assessments of blood counts, liver and kidney function, and disease progression. Safety follow-up and adherence to treatment are closely monitored throughout the study.

Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations