Actively Recruiting
Enfortumab Vedotin and Pembrolizumab With Surgery for 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
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the effects of combining standard treatments enfortumab vedotin and pembrolizumab with surgery to remove all or part of the bladder (cytoreductive cystectomy) and/or the ureter (ureterectomy) in patients with locally advanced or metastatic bladder and upper urothelial tract cancers. This phase IV trial aims to assess progression-free survival and other important outcomes, including overall response and survival rates, surgical success, and treatment safety. The study also explores blood and urine markers to better understand disease relapse and treatment response. Participants receive enfortumab vedotin intravenously on days 1 and 8 and pembrolizumab intravenously on day 1 of each 3-week cycle, continuing for at least four cycles if no disease progression or unacceptable side effects occur. Those who qualify for surgery may undergo cytoreductive cystectomy and/or ureterectomy, with additional metastasis-directed therapy possible as needed. After surgery, patients may continue maintenance treatment with both drugs. Throughout the study, samples and imaging tests such as CT, PET/CT, and MRI are performed regularly. During the study, participants undergo urine and blood collections, imaging scans, and complete questionnaires to monitor quality of life and treatment effects. Safety is closely tracked using standardized criteria, with follow-up visits every 9 weeks for up to 18 months, then every 12 weeks for up to 5 years. The main measure of success is progression-free survival at 12 months, along with overall survival, response rates, and surgical outcomes.
CONDITIONS
Brief 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
- Initial diagnosis within 90 days before planned treatment start
- Variant histologic subtypes allowed if urothelial differentiation is predominant
- Willing and deemed suitable for cytoreductive cystectomy or ureterectomy
- 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/mm³ within 28 days prior to registration
- Platelet count of at least 80,000/mm³ within 28 days prior to registration
- Liver enzymes (ALT or AST) no greater than 3.5 times the upper normal limit within 28 days prior to registration
- Total or direct bilirubin no greater than 3 times the upper normal limit within 28 days prior to registration
- Estimated glomerular filtration rate of at least 15 ml/min within 28 days prior to registration
- Prior chemotherapy for other cancers allowed if over 24 months before enrollment
- All prior surgery-related adverse events resolved to less than grade 2
- Ability and willingness to sign informed consent and complete questionnaires
- Willingness to provide blood and tissue samples for research
- Willingness to return for follow-up visits during active monitoring phase
You will not qualify if you...
- Histologic variants making up more than 50% of tumor or presence of neuroendocrine, micropapillary, or signet ring cell features
- Prior systemic chemotherapy for urothelial carcinoma of the bladder
- Active malignancies requiring recent treatment except certain cured skin, cervical, breast, or prostate cancers
- Systemic chemotherapy or targeted therapy within 2 years prior to study
- Uncontrolled adrenal or cardiovascular diseases
- Active tuberculosis or immunosuppression from organ transplant
- Active autoimmune disease requiring systemic treatment
- Significant liver disease preventing study treatments
- Active HIV infection unless stable and well-controlled
- Active hepatitis B or C infection except certain controlled cases
- Active urinary tract or other urogenital infections
- Interstitial lung disease or non-infectious pneumonitis
- Uncontrolled illness or psychiatric/social issues limiting compliance
- History of bowel perforation risk factors
- Impaired wound healing or prior pelvic radiotherapy
- Recent live virus vaccine within 30 days
- Prior treatment with certain immune checkpoint inhibitors
- History of severe reactions to protein therapies or significant drug allergies
- Participation in another investigational study within 4 weeks
- Incomplete recovery from major surgery or trauma
- Pregnancy, nursing, or unwillingness to use contraception
- Any condition that may interfere with study participation or compliance
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - At least 12 weeks
Participants receive enfortumab vedotin intravenously on days 1 and 8 and pembrolizumab intravenously on day 1 of each 3-week cycle. This treatment repeats for at least 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity.
Multiple visits every 3 weeks for treatment administration
Duration - Variable depending on surgical scheduling
Participants who are surgical candidates may undergo cytoreductive cystectomy and/or ureterectomy. They may also undergo metastasis-directed therapy as part of standard care.
1 to 2 visits depending on surgical procedures
Duration - Variable depending on maintenance therapy duration
After surgery, participants may continue maintenance treatment with enfortumab vedotin and pembrolizumab.
Visits as scheduled for maintenance treatment
Duration - Up to 5 years
After completion of study treatment, participants are followed up for monitoring of progression and health status.
Visits every 9 weeks for up to 18 months, then every 12 weeks up to 5 years
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
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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