Actively Recruiting
Enfortumab Vedotin and Pembrolizumab With Cystectomy and/or Ureterectomy for Locally Advanced or Metastatic Bladder and Upper Urothelial Tract Cancer, CAST-AI Trial
Led by Mayo Clinic · Updated on 2026-02-12
75
Participants Needed
1
Research Sites
520 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This phase IV trial tests the impact of standard of care enfortumab vedotin and pembrolizumab followed by removal of all or part of the bladder (cytoreductive cystectomy) and/or removal of all or part of the tube that carriers urine from the kidneys to the bladder (ureterectomy) on outcomes in patients with bladder and upper urothelial tract that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Giving standard of care enfortumab vedotin and pembrolizumab followed by cytoreductive cystectomy and/or ureterectomy (CC/U) may improve outcomes in patients with locally advanced or metastatic bladder or upper urothelial tract cancer.
CONDITIONS
Official Title
Enfortumab Vedotin and Pembrolizumab With Cystectomy and/or Ureterectomy for Locally Advanced or Metastatic Bladder and Upper Urothelial Tract Cancer, CAST-AI Trial
Who Can Participate
Eligibility Criteria
You may qualify if you...
- 18 years of age or older at the time of informed consent
- Histologically confirmed urothelial carcinoma of the bladder or upper urothelial tract, with lymph node involvement and/or metastasis, diagnosed within 90 days before planned treatment start
- Variant histologic subtypes such as urothelial with squamous or sarcomatoid differentiation are permitted
- Mixed variant histologic subtypes allowed if urothelial differentiation predominates (less than 50% variant)
- Willing to undergo cytoreductive cystectomy or ureterectomy and deemed surgically eligible by the attending urologist
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Hemoglobin level of at least 8.0 g/dL within 28 days prior to registration
- Absolute neutrophil count of at least 1500/mm^3 within 28 days prior to registration
- Platelet count of at least 80,000/mm^3 within 28 days prior to registration
- Alanine aminotransferase (ALT) or aspartate transaminase (AST) less than or equal to 3.5 times the upper limit of normal within 28 days prior to registration
- Total bilirubin less than or equal to 3 times the upper limit of normal within 28 days prior to registration
- Estimated glomerular filtration rate of at least 15 ml/min within 28 days prior to registration
- Prior systemic chemotherapy allowed only if not for urothelial carcinoma and treatment was over 24 months ago
- All adverse events from prior surgery resolved to grade less than 2 per CTCAE version 5.0 before registration
- Signed informed consent form
- Ability to complete questionnaires independently or with assistance
- Willingness to provide mandatory blood and tissue samples for research
- Willing to return to the enrolling institution for follow-up during active monitoring
You will not qualify if you...
- Histologic variants comprising more than 50% of tumor, including neuroendocrine, micropapillary, or signet ring cell features
- Prior systemic chemotherapy for urothelial carcinoma of the bladder
- Active malignancies (other than the study disease) progressing or requiring treatment change in the last 24 months, except fully treated skin cancer, non-invasive cervical cancer, low-risk breast cancer in situ, or localized prostate cancer under specific conditions
- Systemic chemotherapy or targeted small molecule therapy within 2 years prior to study treatment
- Uncontrolled adrenal insufficiency
- Uncontrolled cardiovascular disease in the past 6 months, including unstable angina, heart attack, severe heart failure, cerebrovascular accident, pulmonary embolism, or venous thromboembolism
- Active tuberculosis
- Receiving immunosuppression for organ transplant
- Active autoimmune diseases requiring systemic treatment (except certain skin conditions or hormonal therapies)
- Significant liver disease preventing study treatment
- HIV infection without stable treatment and CD4 count above 350
- Active hepatitis B or C infection, except certain controlled cases
- Active urinary tract infection or uncontrolled urogenital infections
- Interstitial lung disease or active non-infectious pneumonitis
- Uncontrolled illness that limits study compliance
- History of conditions increasing bowel perforation risk
- Impaired wound healing conditions
- Prior pelvic radiotherapy
- Live virus vaccine within 30 days before treatment
- Active infection requiring intravenous therapy within 30 days before treatment
- Prior treatment with certain immune checkpoint inhibitors
- History of severe toxic effects with specific immune agents
- Recovery from major surgery or significant trauma less than 14 days before registration
- Pregnant or nursing persons or those unwilling to use contraception
- Any condition deemed unsuitable by the investigator or limiting protocol compliance
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Actively Recruiting
Research Team
C
Clinical Trials Referral Office
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here