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 (Sep 2026). This Phase 2 trial studies Pemetrexed for metastatic bladder urothelial carcinoma.
Treatment: Pemetrexed — 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.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Chemotherapy
Cancer type
Urothelial Carcinoma
Tumor Agnostic
Biomarker criteria
Required: KMT2D loss
MLL4- protein (KMT2D-gene)
Required: KDM6A loss
UTX-protein (KDM6A-gene)
Required: MTAP loss of function mutation
MTAP loss of function mutation including but not limited to SNVs that cause truncation, CNVs, and indels confirmed by next generation sequencing or immunohistochemistry techniques
Disease stage
Required: Stage IV
Metastatic disease required
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: systemic therapy — metastatic or locally advanced
Patients must have progressive disease despite two prior lines of therapy in the metastatic setting or locally advanced setting unless the patient was not suitable for an approved second line regimen due to intolerance or another clinical factor
Cannot have received: 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 (≤ 3.0 mg/dL if Gilbert's syndrome or liver metastases); AST/ALT ≤ 3 x ULN or ≤ 5 x ULN if documented liver metastases
Cardiac function
NYHA class 2B or better required; patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment
Patients must have adequate organ and bone marrow function as defined: ANC ≥ 1,500/mcL (growth factor allowed); Hgb ≥ 8.5 g/dL (without the need for transfusion within the previous one week); Platelets ≥ 100,000/mL (without the need for platelet transfusion within the previous one week); Total bilirubin ≤ 1.5 x institutional ULN (≤ 3.0 mg/dL if Gilbert's syndrome or liver metastases); AST/ALT ≤ 3 x 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; NYHA class 2B or better required
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
Showing up to 5 US sites.
See all sites on ClinicalTrials.gov →Frequently asked questions
Is NCT06630416 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior pemetrexed disqualifies patients from enrollment.
Does this trial require KMT2D?
Yes, KMT2D loss is a required biomarker for enrollment.
Does this trial require KDM6A?
Yes, KDM6A loss is a required biomarker for enrollment.
Does this trial require MTAP?
Yes, MTAP loss of function mutation is a required biomarker for enrollment.
What disease stage is eligible?
Stage IV is required (metastatic disease required).
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualifyRelated pages