A Phase II Trial to Evaluate Pemetrexed Response in Relation to Tumor Alterations of Gene Status in Patients With Previously Treated Metastatic Urothelial Carcinoma and Other Solid Tumors
Northwestern University
Summary
This phase II trial tests how well pemetrexed works in treating patients with urothelial bladder cancer and other solid tumors that have spread from where they first started (primary site) to other places in the body (metastatic) with mutations that result in a loss of function in the MLL4-protein/KMT2D-gene or UTX-protein/KDM6A-gene or MTAP enzyme. Loss of function due to a genetic mutation means a gene's activity may be reduced or eliminated. Mutations that result in a loss of function in the MLL4-protein or KMT2D-gene are found in 9.96% of all cancers including bladder carcinoma patients, esophageal squamous cell carcinoma and esophageal adenocarcinoma patients. In addition, mutations that result in a loss of function in the UTX-protein or KDM6A-gene are found in approximately 5% of all tumors, including bladder cancers, endometrial cancer, and esophagogastric cancer amongst many other tumor types. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid and may kill tumor cells. Giving pemetrexed may increase response in patients with metastatic urothelial bladder cancer and other solid tumors with the loss of function in the MLL4-protein/KMT2D-gene or UTX-protein/KDM6A-gene or MTAP enzyme.
Description
PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) in patients with metastatic solid tumors and MLL4-protein (KMT2D-gene) or UTX-protein (KDM6A-gene) or MTAP loss of function mutations treated with pemetrexed will assess pemetrexed. SECONDARY OBJECTIVES: I. To determine the progression-free survival (PFS) for patients with metastatic solid tumors and MLL4-protein (KMT2D-gene) or UTX-protein (KDM6A-gene) or MTAP loss of function mutations treated with pemetrexed. II. To determine the overall survival (OS) for patients with metastatic solid tumors and MLL4-protein (KMT2D-gene…