RECRUITING

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

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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)

Quick Facts

Study Start:2024-09-10

Study Completion:2027-07-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06394570

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Urothelial carcinoma of the urinary bladder stage cT2-4a (AJCC 8th edition) N0M0 planned for radical cystectomy. Mixed cell types are allowed as long as urothelial component is \>50% AND no small cell/neuroendocrine or plasmacytoid/signet ring component. 2. 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. 3. Age \>=18. 4. Performance status Eastern Cooperative Oncology Group (ECOG) 0-1 5. Adequate organ and marrow function as defined below: * Platelet count \>=100x109/L * Hemoglobin ≥ 9 g/dL * 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 * No end stage renal disease requiring dialysis allowed 6. 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. * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 7.Ability to understand and the willingness to sign a written informed consent.	1. 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. 2. Baseline \>= Grade 2 sensory or motor neuropathy 3. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to enfortumab vedotin or other agents used in study. 5. 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. 6. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Inclusion Criteria

Exclusion Criteria

1. Urothelial carcinoma of the urinary bladder stage cT2-4a (AJCC 8th edition) N0M0 planned for radical cystectomy. Mixed cell types are allowed as long as urothelial component is \>50% AND no small cell/neuroendocrine or plasmacytoid/signet ring component.
2. 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.
3. Age \>=18.
4. Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
5. Adequate organ and marrow function as defined below:
* Platelet count \>=100x109/L
* Hemoglobin ≥ 9 g/dL
* 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
* No end stage renal disease requiring dialysis allowed
6. 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.
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
7.Ability to understand and the willingness to sign a written informed consent.

1. 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.
2. Baseline \>= Grade 2 sensory or motor neuropathy
3. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to enfortumab vedotin or other agents used in study.
5. 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.
6. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Contacts and Locations

Study Contact

Tian Zhang, MD, MHS

CONTACT

214-648-4180

tian.zhang@utsouthwestern.edu

Amy Rowell

CONTACT

214-645-9688

amy.rowell@utsouthwestern.edu

Study Locations (Sites)

UT Southwestern Medical Center

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: University of Texas Southwestern Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-10

Study Completion Date2027-07-01

Study Record Updates

Study Start Date2024-09-10

Study Completion Date2027-07-01

Terms related to this study

Additional Relevant MeSH Terms

Bladder Cancer