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OncoMatch/Clinical Trials/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

Is NCT06630416 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies Pemetrexed for metastatic bladder urothelial carcinoma.

Phase 2RecruitingNorthwestern UniversityNCT06630416Data as of May 2026

Treatment: PemetrexedThis 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.

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Extracted eligibility criteria

Cancer type

Urothelial Carcinoma

Tumor Agnostic

Biomarker criteria

Required: KDM6A loss of function mutation

Required: KMT2D loss of function mutation

Required: MTAP loss of function mutation

Disease stage

Required: Stage IV (AJCC v8)

Metastatic disease required

metastatic urothelial bladder carcinoma (Arm A) or other metastatic solid malignancy (Arm B)

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Min 2 prior lines

Must have received: systemic chemotherapy — neoadjuvant or systemic

Patients must have progressive disease despite two prior lines of therapy in the metastatic setting unless the patient was not suitable for an approved second line regimen due to intolerance or another clinical factor

Cannot have received: pemetrexed (pemetrexed)

Patients who received prior pemetrexed containing chemotherapy

Lab requirements

Blood counts

ANC  1,500/mcL (growth factor allowed); Hgb  8.5 g/dL (no transfusion within previous one week); Platelets  100,000/mL (no platelet transfusion within previous one week)

Kidney function

Creatinine clearance  45 mL/min/1.73 m^2 using Cockcroft and Gault formula

Liver function

Total bilirubin  1.5 x institutional ULN (except Gilbert's syndrome or liver metastases, then  3.0 mg/dL); AST/ALT  3 x ULN or  5 x ULN if liver metastases

Cardiac function

Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible, patients should be class 2B or better.

ANC  1,500/mcL (growth factor allowed); Hgb  8.5 g/dL (without the need for transfusion within the previous one week); Platelets (PLT)  100,000/mL (without the need for platelet transfusion within the previous one week); Total bilirubin  1.5 x institutional ULN, except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin  3.0 mg/dL; AST (SGOT)  3 x institutional ULN or  5 x ULN if documented liver metastases are present; ALT (SGPT)  3 x institutional ULN or  5 x ULN if documented liver metastases are present; Creatinine clearance  45 mL/min/1.73 m^2 using the standard Cockcroft and Gault formula; cardiac risk assessment using NYHA Functional Classification, class 2B or better

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Northwestern University · Chicago, Illinois
  • Northwestern Medicine Orland Park · Orland Park, Illinois

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