Enfortumab Vedotin and Stereotactic Radiation for Localized, Cisplatin Ineligible Muscle Invasive Bladder Cancer — STAR-EV  

Bladder Cancer Clinical Trial

Official title: Stereotactic Treatment With neoAdjuvant Radiotherapy and Enfortumab Vedotin: a Phase I/II Study With Safety Lead-In for Localized, Cisplatin Ineligible, Muscle Invasive Bladder Cancer (STAR-EV)

Status Not yet recruiting

Clinical Trial Summary

STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for muscle invasive bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens:

Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15

Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.

Clinical Trial Description

STAR EV is a phase I/II trial with safety lead in, designed to assess safety and preliminary efficacy signal in improving pathologic complete response by adding stereotactic radiation to neoadjuvant enfortumab vedotin. Participants will be adult patients with urothelial predominant bladder cancer ineligible for neoadjuvant cisplatin-based therapy (based on provider assessment) and planned for radical cystectomy.

All participants will undergo the same treatment:

• Enfortumab vedotin (PADCEV) 1.25mg/kg (max 125mg) IV Day 1, 8 q21 day cycle x 3 cycles

• Radiation: Stereotactic radiotherapy to bladder (partial bladder volume preferred) 5 fractions; either sequential to EV treatment or concurrent with EV treatment

• Surgery: Standard of care radical cystectomy and pelvic lymph node dissection with urinary diversion per surgeon discretion.

The study will use a patient safety lead-in incorporating escalation of EV-RT from sequential to concurrent use with pre-defined stopping rules according to treatment-related adverse event (TRAE) rate of grade 3 or above. Primary endpoints are related to safety (maximum tolerated dose "regimen" based on dose limiting toxicities (DLTs) observed) and pathologic complete response rate at the time of surgery. Subjects will be followed for one year following cystectomy, or completion of neoadjuvant therapy for any subject who does not undergo cystectomy for any reason. ;

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

• NCT number: NCT06394570
• Study type: Interventional
• Source: University of Texas Southwestern Medical Center
• Contact: Tian Zhang, MD, MHS
• Phone: 214-648-4180
• Email: tian.zhang@utsouthwestern.edu
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2024
• Completion date: July 1, 2027