Combining enfortumab vedotin with radiation for bladder cancer treatment

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This trial evaluates the combination of enfortumab vedotin and stereotactic radiation as a neoadjuvant treatment for patients with muscle invasive bladder cancer who are ineligible for cisplatin-based chemotherapy. The study employs a dose escalation approach to determine the safety and efficacy of the treatment regimen, which includes administering enfortumab vedotin followed by radiation therapy. Participants will undergo three cycles of treatment before proceeding to radical cystectomy surgery. The primary endpoints focus on safety and the rate of pathologic complete response at the time of surgery.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Urothelial carcinoma of the urinary bladder stage cT1-4a (AJCC 8th edition) N0M0 planned for radical cystectomy.
2. For cR1 staged patients. the patient must have high grade disease AND be appropriate for cystectomy.
3. 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.
4. Age \>=18.
5. Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
6. 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
7. 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.

7a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

* 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).

  8\. Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

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.

Where it's running

• UT Southwestern Medical Center
  Dallas, Texas, United States Recruiting

Study contacts

• Study coordinator: Tian Zhang, MD, MHS
• Email: tian.zhang@utsouthwestern.edu
• Phone: 214-648-4180

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Bladder cancer: test a biomarker-guided plan after neoadjuvant therapy

  This phase 2 study tests a biomarker- and response-guided plan to preserve the bladder in patients with muscle-invasive bladder cancer after neoadjuvant therapy.

  Recruiting Phase 2 Fox Chase Cancer Center · Philadelphia, Pennsylvania · NCT07908979

• Adding MK-3120 to enfortumab vedotin and pembrolizumab for advanced urothelial (bladder) cancer

  This study tests whether adding the investigational drug MK-3120 to standard enfortumab vedotin plus pembrolizumab helps people with locally advanced or metastatic urothelial (bladder) cancer.

  Recruiting at 17 sites Phase 1/2 Merck Sharp & Dohme LLC · San Francisco, California and 16 other locations · NCT07232602

• Combining enfortumab vedotin and pembrolizumab with radiation for muscle invasive bladder cancer

  This study is testing a new combination of a drug and radiation therapy to see if it helps people with muscle invasive bladder cancer who want to avoid surgery.

  Recruiting Phase 1/2 University of California, San Francisco · San Francisco, California · NCT06470282

• Combination therapy for high grade upper tract urothelial cancer patients refusing surgery

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  Recruiting at 2 sites Phase 2 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Washington D.C., District of Columbia and 1 other locations · NCT05656235

• Sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial cancer

  This trial tests whether combining sacituzumab govitecan and enfortumab vedotin, with pembrolizumab in some patients, helps people with metastatic urothelial carcinoma who have progressed after platinum chemotherapy and PD‑1/PD‑L1 inhibitors.

  Recruiting Phase 1/2 Dana-Farber Cancer Institute · Boston, Massachusetts · NCT04724018

• Urinary Cell-Free DNA Test for Urothelial Cancer Origin

  This study tests a urine-based cell-free DNA test to help diagnose urothelial cancer and identify whether it started in the bladder or upper urinary tract in adults.

  Recruiting Ruijin Hospital · Shanghai · NCT07888374

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.