CAST-AI: Cystectomy After Systemic Therapy With ADC and Immunotherapy
Mayo Clinic
Summary
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.
Description
PRIMARY OBJECTIVE: I. To evaluate progression-free survival at 12 months in patients undergoing treatment with enfortumab vedotin and pembrolizumab (EV/Pembro) and CC/U with or without metastasis-directed therapy (MDT). SECONDARY OBJECTIVES: I. To evaluate overall response rate (ORR). II. To evaluate surgical candidacy rate (defined as the proportion of patients in the study who undergo cystectomy and/or ureterectomy) and pathologic complete response and downstaging (ypT0, ypTis/Ta) at time of CC/U. III. To evaluate progression-free survival (PFS). IV. To evaluate overall survival (OS). V.…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 18 years of age or older at the time of informed consent * Histologically proven urothelial carcinoma \[American Joint Committee on Cancer (AJCC) 2017\] of the bladder (BCa) or upper urothelial tract (UTUC), N+ and/or M+. Initial diagnosis must be within 90 days of planned date for treatment initiation * The following variant histologic subtypes are permitted in any amount * Urothelial with squamous differentiation * Urothelial with sarcomatoid differentiation * Mixed variant histologic subtypes are permitted if urothelial differentiation is predominant (e.…
Interventions
- ProcedureBiospecimen Collection
Undergo urine and blood sample collection
- ProcedureComputed Tomography
Undergo CT or PET/CT
- ProcedureCystectomy
Undergo cytoreductive cystectomy
- DrugEnfortumab Vedotin
Given IV
- ProcedureLocal Therapy
Undergo MDT
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- BiologicalPembrolizumab
Given IV
Location
- Mayo Clinic in RochesterRochester, Minnesota