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

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.