MODERN: An Integrated Phase 2/3 and Phase 3 Trial of MRD-Based Optimization of ADjuvant ThErapy in URothelial CaNcer
National Cancer Institute (NCI)
Summary
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.
Description
PRIMARY OBJECTIVES: I. To compare the ctDNA clearance proportion (i.e., ctDNA positive \[+\] --\> ctDNA negative \[-\]) at 12 weeks in patients enrolled in Cohort A treated with adjuvant nivolumab versus nivolumab + relatlimab (phase 2 portion). II. To compare overall survival in patients enrolled in Cohort A treated with adjuvant nivolumab versus nivolumab + relatlimab (phase 3 portion). III. To compare disease-free survival in patients enrolled in Cohort B randomized to immediate treatment with nivolumab to those randomized to surveillance with subsequent treatment with nivolumab only upo…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * PRE-REGISTRATION (STEP 0): Histologically confirmed muscle-invasive urothelial carcinoma of the urethra, bladder, ureter or renal pelvis * PRE-REGISTRATION (STEP 0): 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 (STEP 0): Radical surgery (cystectomy with lymph node dissection or nephroureterectomy or ureterectomy…
Interventions
- ProcedureBiospecimen Collection
Undergo collection of tissue and blood
- OthercfDNA or ctDNA Measurement
Undergo ctDNA surveillance
- ProcedureComputed Tomography
Undergo CT
- ProcedureCystoscopy
Undergo cystoscopy
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- BiologicalNivolumab
Given IV
- OtherQuestionnaire Administration
Locations (494)
- Cancer Center at Saint Joseph'sPhoenix, Arizona
- Mayo Clinic Hospital in ArizonaPhoenix, Arizona
- University of Arizona Cancer Center-Orange Grove CampusTucson, Arizona
- Banner University Medical Center - TucsonTucson, Arizona
- University of Arizona Cancer Center-North CampusTucson, Arizona
- Highlands Oncology Group - FayettevilleFayetteville, Arkansas