NCT06630416

Pemetrexed Response in Relation to Tumor Alterations of Gene Status for the Treatment of Patients With Metastatic Urothelial Bladder Cancer and Other Solid Tumors

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) in patients with metastatic solid tumors and MLL4-protein (KMT2D-gene) and 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) and 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) and UTX-protein (KDM6A-gene) or MTAP loss of function mutations treated with pemetrexed. III. To determine the duration of response (DOR) for patients with metastatic solid tumors and MLL4-protein (KMT2D-gene) and UTX-protein (KDM6A-gene) or MTAP loss of function mutations treated with pemetrexed. IV. To assess safety and tolerability of pemetrexed in patients with metastatic solid treated with pemetrexed. EXPLORATORY OBJECTIVE: I. To collect plasma and urine samples for future translational studies to determine mechanisms of resistance to pemetrexed. OUTLINE: Patients receive pemetrexed intravenously (IV) over 10 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and urine sample collection on study as well as computed tomography (CT) throughout the trial. After completion of study treatment, patients are followed up every 3 months for up to 12 months.

Conditions

• Metastatic Bladder Urothelial Carcinoma
• Metastatic Malignant Solid Neoplasm
• Stage IV Bladder Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood and urine sample collection
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Pemetrexed	Given IV

Timeline

• Start date: 2024-11-27
• Primary completion: 2029-05-10
• Completion: 2030-05-10
• First posted: 2024-10-08
• Last updated: 2026-02-24

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study