Ignite Creation Date:
2025-12-24 @ 1:17 PM
Ignite Modification Date:
2025-12-29 @ 10:13 PM
Study NCT ID:
NCT06764095
Status:
RECRUITING
Last Update Posted:
2025-09-15
First Post:
2024-12-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
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
Sponsor:
Mayo Clinic
Organization:
Study Overview
Official Title:
CAST-AI: Cystectomy After Systemic Therapy With ADC and Immunotherapy
Status:
RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
Detailed 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. To evaluate the toxicity profile as assessed per Common Terminology Criteria for Adverse Events (CTCAE).
CORRELATIVE OBJECTIVES:
I. Determine the prognostic value of exosomes and circulating cell-free deoxyribonucleic acid (cfDNA) minimal residual disease (MRD) markers.
II. Determine the prognostic value of exosomes and cfDNA as early indicators of disease relapse.
III. Characterize duration of response. IV. Evaluate treatment tolerability as assessed per Patient Reported Outcomes (PRO) (CIPN20).
OUTLINE:
Patients receive standard of care enfortumab vedotin intravenously (IV) over 30 minutes on day 1 and day 8 and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for at least 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Patients who are surgical candidates may then undergo cytoreductive cystectomy and/or ureterectomy. Patients may also undergo MDT at any time per standard of care. After surgery, patients may then continue to receive maintenance enfortumab vedotin and pembrolizumab. Additionally, patients undergo urine and blood sample collection, computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up every 9 weeks for up to 18 months, then every 12 weeks up to 5 years.
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. To evaluate the toxicity profile as assessed per Common Terminology Criteria for Adverse Events (CTCAE).
CORRELATIVE OBJECTIVES:
I. Determine the prognostic value of exosomes and circulating cell-free deoxyribonucleic acid (cfDNA) minimal residual disease (MRD) markers.
II. Determine the prognostic value of exosomes and cfDNA as early indicators of disease relapse.
III. Characterize duration of response. IV. Evaluate treatment tolerability as assessed per Patient Reported Outcomes (PRO) (CIPN20).
OUTLINE:
Patients receive standard of care enfortumab vedotin intravenously (IV) over 30 minutes on day 1 and day 8 and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for at least 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Patients who are surgical candidates may then undergo cytoreductive cystectomy and/or ureterectomy. Patients may also undergo MDT at any time per standard of care. After surgery, patients may then continue to receive maintenance enfortumab vedotin and pembrolizumab. Additionally, patients undergo urine and blood sample collection, computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up every 9 weeks for up to 18 months, then every 12 weeks up to 5 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: