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

Conditions

• Muscle Invasive Bladder Urothelial Carcinoma
• Muscle Invasive Renal Pelvis Urothelial Carcinoma
• Muscle Invasive Ureter Urothelial Carcinoma
• Muscle Invasive Urethral Urothelial Carcinoma
• Stage II Bladder Urothelial Carcinoma AJCC v6 and v7
• Stage III Bladder Urothelial Carcinoma AJCC v6 and v7
• Stage IV Bladder Urothelial Carcinoma AJCC v7

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo collection of tissue and blood
• cfDNA or ctDNA Measurement — OTHER
  Undergo ctDNA surveillance
• Computed Tomography — PROCEDURE
  Undergo CT
• Cystoscopy — PROCEDURE
  Undergo cystoscopy
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Nivolumab — BIOLOGICAL
  Given IV
• Questionnaire Administration — OTHER
  Ancillary studies
• Relatlimab — BIOLOGICAL
  Given IV

Study Details

This phase II/III trial examines whether patients who have undergone surgical removal of bladder, kidney, ureter or urethra, but require an additional treatment called immunotherapy to help prevent their urinary tract (urothelial) cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and relatlimab, can help the body's immune system to attack the cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of urothelial cancer patients who have undergone surgical removal of their bladder, kidney, ureter or urethra.

Key Dates

Start date

Feb 2, 2024

Status verified

Apr 2026

Primary completion

Sep 2, 2030

Completion

Sep 2, 2030

Study Design

Enrollment

992 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Cohort A, Arm I (nivolumab)
  Patients in Cohort A, Arm I receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI and may undergo cystoscopy throughout the trial.
• Experimental: Cohort A, Arm II (nivolumab, relatlimab)
  Patients in Cohort A, Arm II receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI and may undergo cystoscopy throughout the trial.
• Active Comparator: Cohort B, Arm III (nivolumab)
  Patients in Cohort B, Arm III receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI and may undergo cystoscopy throughout the trial.
• Experimental: Cohort B, Arm IV (ctDNA surveillance, nivolumab)
  Patients in Cohort B, Arm IV undergo ctDNA surveillance consisting of collection of tissue and blood during screening and collection of blood only on study and during follow up. Patients who convert to ctDNA(+) during surveillance then receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI and may undergo cystoscopy throughout the trial.

Primary Outcome Measure

Proportion of patients who are circulating tumor DNA negative (ctDNA[-]) (Cohort A Phase II) [ Time Frame: At week 12 from treatment start date ]

Locations (490)

Find similar trials in Phoenix, AZ

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