Enfortumab Vedotin and Stereotactic Radiation for Localized, Cisplatin Ineligible Muscle Invasive Bladder Cancer

NCT06394570 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STU-2024-0374
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) Regimen

  A standard 3 + 3 dose escalation schedule will be used for all escalations. Enfortumab Vedotin will be given for three 21 day cycles. Radiation therapy will be administered at dose level 0, level 1 or level 2.

  From initiation of Enfortuman Vedotin treatment until post neoadjuvant therapy visit (approximately 120 days)

• Pathologic Complete response rate at radical cystectomy

  Rate of complete pathologic response in bladder tumor biopsy at cystectomy according to postsurgical staging.

  At radical cystectomy following completion of neoadjuvant therapy (approximately 6 weeks after completion of EV treatment)

Secondary Outcomes (2)

• Adverse Events

  From initiation of neoadjuvant therapy to completion of final post treatment study visit (approximately 4 months)

• Rate of pathologic downstaging in the bladder

  At radical cystectomy following completion of neoadjuvant therapy (approximately 6 weeks after completion of EV treatment)

Study Arms (3)

Dose Level 0

EXPERIMENTAL

Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and sequential Radiation Therapy starting on Cycle 3 Day 21 of EV treatment (32.5 Gray in 5 fractions)

Drug: Enfortumab vedotin

Dose Level 1

EXPERIMENTAL

Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 2 Day 15 of EV treatment (32.5 Gray in 5 fractions)

Drug: Enfortumab vedotin

Dose Level 2

EXPERIMENTAL

Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 1 Day 15 of EV treatment (32.5 Gray in 5 fractions)

Drug: Enfortumab vedotin

Interventions

Enfortumab vedotin DRUG

Enfortumab Vedotin administered 1.25mg/kg (max 125mg) IV on Day 1 and Day 8 of each 21 day cycle x 3 cycles

Also known as: PADCEV

Dose Level 0; Dose Level 1; Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Urothelial carcinoma of the urinary bladder stage cT2-4a (AJCC 8th edition) N0M0 planned for radical cystectomy. Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
• Ineligibility for cisplatin-based chemotherapy based on treating physician assessment and any of the following "Galsky criteria": renal insufficiency (Creatinine Clearance \<60ml/min by standard institutional calculation method), \>=grade 2 peripheral neuropathy, \>=grade 2 hearing loss, New York Heart Association (NYHA) class III heart failure; a combination of these; or patient refusal.
• Age \>=18.
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
• Adequate organ and marrow function as defined below:
• Hematologic:
• Absolute neutrophil count (ANC) \>=1500/mm3
• Platelet count \>=100x109/L
• Hemoglobin ≥ 9 g/dL
• Hepatic:
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Renal:
• No end stage renal disease requiring dialysis allowed
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months following completion of study neoadjuvant therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• No prior systemic therapy (except prior therapy for non-muscle invasive bladder cancer \>12 prior to registration) for bladder cancer or prior pelvic radiotherapy. Prior intra-vesical therapies are allowed, including Bacillus Calmette-Guerin (BCG) for non-muscle invasive bladder cancer. Prior chemotherapy for other cancers is allowed if given \>=1 year prior to study registration.
• Baseline \>= Grade 2 sensory or motor neuropathy
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to enfortumab vedotin or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

enfortumab vedotin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Tian Zhang, MD, MHS

CONTACT

214-648-4180; tian.zhang@utsouthwestern.edu

Amy Rowell

CONTACT

214-645-9688; amy.rowell@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor- Internal Medicine

Model Details: Safety lead-in which will assess safety of study therapy in a rule-based "escalation" approach, using the classic "3+3" design.

Study Record Dates

• First Submitted: April 27, 2024
• First Posted: May 1, 2024
• Study Start: September 10, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 15, 2025

Record last verified: 2025-09

Locations

US (1)