Enfortumab Vedotin and Pembrolizumab With Cystectomy and/or Ureterectomy for Locally Advanced or Metastatic Bladder and Upper Urothelial Tract Cancer, CAST-AI Trial

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.

Conditions

• Locally Advanced Bladder Urothelial Carcinoma
• Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma
• Metastatic Bladder Urothelial Carcinoma
• Metastatic Renal Pelvis and Ureter Urothelial Carcinoma
• Stage III Bladder Cancer AJCC v8
• Stage IV Bladder Cancer AJCC v8
• Stage IV Renal Pelvis and Ureter Cancer AJCC v8

Interventions

PROCEDURE

Biospecimen Collection

Undergo urine and blood sample collection

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

PROCEDURE

Cystectomy

Undergo cytoreductive cystectomy

DRUG

Enfortumab Vedotin

Given IV

PROCEDURE

Local Therapy

Undergo MDT

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

BIOLOGICAL

Pembrolizumab

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

OTHER

Questionnaire Administration

Ancillary studies

PROCEDURE

Ureterectomy

Undergo ureterectomy

Sponsors & Collaborators

• Mayo Clinic

  lead OTHER

Principal Investigators

• Jacob J. Orme, MD, PhD · Mayo Clinic in Rochester

• Paras H. Shah, MD · Mayo Clinic in Rochester

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-08

Primary Completion

2034-12-31

Completion

2034-12-31

FDA Drug

Yes

Countries

• United States

Study Locations