Consolidative local surgery for oligo‑metastatic urothelial (bladder) cancer

A Phase II Study of Consolidative Local Therapy in Patients With Locally Advanced or Oligo-metastatic Urothelial Carcinoma (la/mUC) Following Treatment Response to Systemic Therapy With or Without Metastasis-directed Radiotherapy

This trial will see if adding surgery to remove the bladder tumor (and any resectable metastases) after a good response to enfortumab vedotin–based therapy helps people with locally advanced or oligo‑metastatic urothelial cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Yale University (Academic / other)
• Drugs / interventions: enfortumab
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT07048457 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase 2 trial enrolling adults with locally advanced or oligo‑metastatic urothelial carcinoma who have shown stable disease or a response to first-line enfortumab vedotin–based systemic therapy. Eligible participants who are surgical candidates will undergo radical cystectomy with standard bilateral pelvic lymph node dissection and urinary diversion, and surgeons may resect non‑irradiated metastatic lesions when feasible. The protocol examines outcomes after consolidative local therapy to see whether removing the primary tumor and resectable metastatic sites improves disease control compared with historical expectations. Enrollment is at Yale University and requires adequate organ function and ECOG performance status 0–1.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed locally advanced or oligo‑metastatic urothelial carcinoma (≤5 distinct metastatic lesions) who had stable or responsive disease to enfortumab vedotin–based first‑line therapy, are surgical candidates, and have ECOG 0–1 and adequate organ function are ideal candidates.

Not a fit: Patients with widespread (>5) or unresectable metastases, poor performance status, significant organ dysfunction, or progressive disease on first‑line therapy are unlikely to benefit from this consolidative surgical approach.

Why it matters

Potential benefit: If successful, this approach could improve disease control and possibly extend survival for patients with limited metastatic urothelial carcinoma by removing residual sites of cancer after systemic therapy.

How similar studies have performed: Consolidative local therapy and metastasectomy have shown benefit in selected oligometastatic patients in other cancers, but data specific to urothelial carcinoma after enfortumab vedotin are limited and largely early-stage.

Eligibility criteria

Inclusion Criteria:

1. Be at least 18 years of age.
2. Have provided informed consent.
3. Have ECOG Performance status of 0 or 1.
4. Be surgical candidate for extirpative surgery of primary site with standard bilateral pelvic lymph node dissection and urinary diversion at the discretion of urological oncologist.
5. If applicable, must be a surgical candidate for resection of non-irradiated metastatic lesion(s) at the discretion of the treating surgeon.
6. Have adequate organ function as defined by:

   1. Hgb \>9.0 ng/dL.
   2. WBC \>3.0 K/mcL.
   3. PLT \>100 K /mcL.
   4. AST \<3.0 x ULN U/L.
   5. ALT \<3.0 x ULN U/L.
   6. Total Bilirubin \<2.0 x UNL mg/dL.

   Disease characteristics:
7. Have histologically confirmed diagnosis of locally advanced or oligo-metastatic urothelial carcinoma defined by presence of five or few distinct metastatic lesions at the time of diagnosis of metastatic disease.
8. If variant histology present, it must be \<50% and UC must be predominant.
9. Must have begun the first cycle of enfortumab-vedotin-based first-line therapy at least three months prior to the surgery and have continued therapy and the treatment duration must have not exceeded six months from the start of the first cycle. Treatment interruption, modification and discontinuation due to adverse events are allowed. Metastasis-directed radiotherapy (MDRT) is allowed.
10. The most recent restaging scan prior to signing ICD must show stable disease, partial response or complete response per treating investigator-assessed RECIST v1.1. In case of stable disease or partial response, MDRT is highly recommended. Enrollment of such participants should be discussed with the PI.

Exclusion Criteria:

Participants who meet any of the following criteria will be excluded from study entry.

1. Received systemic anti-cancer therapy within three weeks prior to the surgery.
2. Received radiotherapy within two weeks prior to the surgery.
3. Have a positive serum pregnancy test or women who are breastfeeding.
4. Have other concurrent medical, surgical or psychiatric conditions that, in the treating investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
5. Have any medical condition that, in the treating investigator's opinion, poses an undue risk to the participant's participation in the study.
6. Have history of central nervous system (CNS) metastasis and/or leptomeningeal metastasis.

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Fed Ghali, MD — Yale University
• Study coordinator: Laura Kane

Conditions Locally Advanced Urothelial Carcinoma; Oligo-metastaic Urothelial Carcinoma; demonstrated stable or responsive disease to first-line systemic therapy