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

ConditionsLocally Advanced Bladder Urothelial CarcinomaLocally Advanced Renal Pelvis and Ureter Urothelial CarcinomaMetastatic Bladder Urothelial CarcinomaMetastatic Renal Pelvis and Ureter Urothelial CarcinomaStage III Bladder Cancer AJCC v8Stage IV Bladder Cancer AJCC v8Stage IV Renal Pelvis and Ureter Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Presence of urothelial carcinoma with histologic variants comprising > 50% of histology

Any amount: neuroendocrine, micropapillary, or signet ring cell features

Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time (excluding intravesicular therapies)

Skin cancer (non-melanoma or melanoma) that is considered completely cured

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo urine and blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT or PET/CT

  • Cystectomy

    Procedure/Surgery

    Undergo cytoreductive cystectomy

  • Enfortumab Vedotin

    Drug

    Given IV

  • Local Therapy

    Procedure/Surgery

    Undergo MDT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Ureterectomy

    Procedure/Surgery

    Undergo ureterectomy

Treatment groups

75 Participants
are divided into 1 treatment group
Group A: Treatment (enfortumab vedotin, pembrolizumab)Experimental treatment 10 interventions

Trial outcomes

Primary outcomes

1

Progression-free survival (PFS) at 12 months

Will be calculated as the number of patients who are alive and progression-free at 12 months after study enrollment. Progression will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria.

Time frame
At 12 months

Secondary outcomes

1

PFS overall

PFS will be defined as the time from study registration to the date of death due to any cause or progressing disease, whichever occurs first. Progression will be determined by RECIST v1.1 criteria.

Time frame
Up to 5 years
2

Overall survival (OS)

OS will be defined as time from the date of registration to the date of death from any cause

Time frame
Up to 5 years
3

Overall response rate (ORR)

ORR will be defined as confirmed complete response (CR) or partial response (PR) according to RECIST v 1.1 criteria, assessed at the time of cytoreductive cystectomy and/or ureterectomy (CC/U) or at time of best response during treatment.

Time frame
Up to 5 years
4

Surgical candidacy rate

Will be defined as the proportion of patients in the Modified Intent-to-Treat (mITT) population who undergo CC/U \[cytoreductive cystectomy (CC) and/or ureterectomy (U)\].

Time frame
Up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

Source ClinicalTrials.gov
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