What is this trial studying for urothelial cancer?

This trial is studying whether a blood test measuring tumor DNA can guide the use of immunotherapy after surgery to help prevent urothelial cancer from returning. It also evaluates different immunotherapy treatments, including nivolumab alone or combined with relatlimab, to see how they affect survival and disease progression. The National Cancer Institute sponsors this research.

Who may be eligible for this urothelial cancer clinical trial?

Adults 18 years or older who have had surgery to remove the bladder, kidney, ureter, or urethra due to muscle-invasive urothelial cancer may be eligible. Participants must be free of active cancer after surgery and meet health criteria such as adequate blood counts and organ function. Both males and females can participate. Please review eligibility criteria for more details.

Is there any cost to participate in this urothelial cancer clinical trial?

Study-related care, including the immunotherapy treatments and all trial visits, is provided at no cost. Personal travel or lodging expenses may vary and are not guaranteed to be covered. Participants should plan accordingly when considering involvement in the trial.

Actively Recruiting

Phase 2

Phase 3

Age: 18Years +

All Genders

ID05987241

MODERN An Integrated Phase 23 and Phase 3 Trial of MRD-Based Optimization of Adjuvant Therapy in Urothelial Cancer

Led by National Cancer Institute (NCI) · Updated on 2026-06-03

992

Participants Needed

498

Research Sites

N/A

Total Duration

AI-Summary

What this Trial Is About

Researchers are studying patients who have had surgery to remove the bladder, kidney, ureter, or urethra due to muscle-invasive urothelial cancer. This trial evaluates whether a blood test measuring circulating tumor DNA ctDNA can identify those who need additional immunotherapy to prevent cancer recurrence. The study also compares treatment with nivolumab alone versus nivolumab combined with relatlimab, focusing on survival and disease progression outcomes. Participants are assigned to one of two groups based on their ctDNA blood test results. Those with positive ctDNA are randomized to receive either nivolumab alone or nivolumab plus relatlimab, each given intravenously every 28 days for up to 12 cycles. Participants with negative ctDNA are randomized to receive immediate nivolumab or be monitored closely with ctDNA surveillance and start nivolumab only if their ctDNA becomes positive. Throughout the study, patients undergo tissue and blood collection, imaging scans like CT or MRI, and may have cystoscopy. During the trial, participants are regularly monitored with blood tests for ctDNA, imaging, and questionnaires to assess quality of life and fatigue. The study measures the proportion of patients clearing ctDNA after treatment, overall survival, and disease-free survival for up to 5 years. Safety of the treatments is also assessed. After treatment, follow-up visits occur at specific weeks up to nearly 5 years to continue monitoring health and outcomes.

CONDITIONS

Brief Title

Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study

Who Can Participate

Age: 18Years +

All Genders

Eligibility Criteria

You may qualify if you...

Histologically confirmed muscle-invasive urothelial carcinoma of the urethra, bladder, ureter, or renal pelvis
Radical surgery (cystectomy with lymph node dissection, nephroureterectomy, or ureterectomy) performed 3 to 16 weeks before pre-registration
No gross cancer at surgical margins and no evidence of residual cancer or metastasis after surgery
Age 18 years or older
ECOG performance status 0 to 2
No postoperative adjuvant systemic therapy or radiation after surgery
No treatment with other investigational agents within 4 weeks before pre-registration
No previous treatment with LAG-3 blockade therapy
Adequate blood counts and organ function including ANC ≥ 1,200/mm³, platelet count ≥ 100,000/mm³, hemoglobin ≥ 8 g/dL, creatinine ≤ 1.5 x ULN or creatinine clearance > 30 mL/min, AST/ALT ≤ 3 x ULN, total bilirubin ≤ 1.5 x ULN (except Gilbert Syndrome)
Negative pregnancy test for women of childbearing potential
No current hemodialysis
No current or prior history of myocarditis
No history of severe immune-related adverse events with prior PD-1/PD-L1 blockade
No active autoimmune disease affecting vital organs or requiring immunosuppressive treatment except certain controlled conditions
No current pneumonitis or recent history requiring steroids
No active hepatitis B or C infection; treated and cured allowed
HIV-positive patients with undetectable viral load on treatment allowed
No concurrent anti-cancer therapy or immunosuppressive agents (except allowed corticosteroids)

You will not qualify if you...

Partial cystectomy as definitive therapy
Gross cancer at surgical margins
Evidence of residual cancer or metastasis after surgery
Pregnancy or nursing
Treatment with other investigational agents within 4 weeks before pre-registration
Previous treatment with LAG-3 blockade therapy
Current hemodialysis
History of myocarditis
History of grade 3 or higher immune-related adverse events with prior PD-1/PD-L1 blockade
Active autoimmune disease affecting vital organs or requiring systemic immunosuppressive treatment (excluding certain controlled conditions)
Current pneumonitis or pneumonitis requiring steroids within past 5 years
Active hepatitis B or C infection without treatment or undetectable viral load
Concurrent antineoplastic therapy including hormonal cancer treatments
Current systemic immunosuppressive therapy (except permitted corticosteroids)

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