NCT05987241 · National Cancer Institute (NCI)
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
What this study is about
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.
View original scientific description
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.
Interventions
PROCEDURE
Biospecimen Collection
Undergo collection of tissue and blood
OTHER
cfDNA or ctDNA Measurement
Undergo ctDNA surveillance
PROCEDURE
Computed Tomography
Undergo CT
PROCEDURE
Cystoscopy
Undergo cystoscopy
PROCEDURE
Magnetic Resonance Imaging
Undergo MRI
BIOLOGICAL
Nivolumab
Given IV
OTHER
Questionnaire Administration
Ancillary studies
BIOLOGICAL
Relatlimab
Given IV
Primary outcome measures
Proportion of patients who are circulating tumor DNA negative (ctDNA[-]) (Cohort A Phase II)
Time frame: At week 12 from treatment start date
Will be determined for each treatment arm as the number of patients who are ctDNA(-) after 12 weeks of treatment divided by the total number of patients on the treatment arm. Patients who do not have a 12-week ctDNA result will be deemed to be ctDNA(+). The comparison of the proportions of patients who are ctDNA(-) after 12 weeks of treatment between the two arms will be performed with a chi-square test.
Overall survival (OS) (Cohort A Phase III)
Time frame: From randomization until death due to any cause, assessed up to 5 years after completion of study treatment
The analysis will be performed using a stratified log-rank test that uses the specified stratification variables. An additional analysis will be perform using a stratified Cox regression model to generate the point estimate and 90% confidence interval for the hazard ratio (HR) (comparing Arm 2 to Arm 1).
Disease-Free Survival (DFS) (Cohort B)
Time frame: From randomization until confirmed disease recurrence as assessed by the treating physician or death due to any cause, assessed up to 5 years after completion of study treatment
A stratified Cox model (using the randomization stratification variables will be used to generate a 90% confidence interval (CI) for the HR. If the 90% CI does not contain 1.39, Arm 4 (surveillance with ctDNA serial testing to determine whether patient is treated with nivolumab) will be deemed to be non-inferior to treating patients immediately with nivolumab.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- PRE-REGISTRATION: Histologically confirmed muscle-invasive urothelial carcinoma of the urethra, bladder, ureter or renal pelvis
- PRE-REGISTRATION: Variant histology, including neuroendocrine differentiation, sarcomatoid, micropapillary, glandular, trophoblastic, Mullerian, is allowed if urothelial cancer is predominant histology (any amount of squamous differentiation is allowed provided the tumor is not a pure squamous cell cancer)
- PRE-REGISTRATION: Patient must have had radical surgery (i.e., cystectomy and lymph node dissection or nephroureterectomy or ureterectomy) ≥ 3 weeks, but ≤ 12 weeks prior to pre-registration. Patients who have had a partial cystectomy as definitive therapy are not eligible
- PRE-REGISTRATION: No gross cancer at the surgical margins. Microscopic invasive urothelial carcinoma at the surgical margins (i.e., "positive margins") are allowed. Carcinoma in situ (CIS) at margins is considered negative margins
- PRE-REGISTRATION: No evidenc
Where
- Phoenix, Arizona
- Tucson, Arizona
- Fayetteville, Arkansas
- Rogers, Arkansas
- Springdale, Arkansas
- Anaheim, California
- Baldwin Park, California
- Bellflower, California
- Dublin, California
- Fontana, California
- Fremont, California
- Fresno, California
And 362 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 7, 2026 · Source of record for eligibility and locations