Consolidative Local Therapy (CLT) in Oligo-metastatic Urothelial Carcinoma

NCT07048457 | Recruiting Phase 2 DMC

• 1 other identifier: 2000039076
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the therapeutic benefit of consolidative local therapy with extirpative surgery for participants with locally advanced or oligo-metastatic urothelial carcinoma that have disease control with enfortumab vedotin-based systemic therapy and surgically resectable or previously radiated metastatic sites.

Conditions

Locally Advanced Urothelial Carcinoma; Oligo-metastaic Urothelial Carcinoma

Keywords

demonstrated stable or responsive disease to first-line systemic therapy

Outcome Measures

Primary Outcomes (1)

• 12-Month Progression-Free Survival in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma

  The primary outcome measure for this study is to evaluate the 12-month progression-free survival of consolidative therapy in participants with locally advanced or oligo-metastatic urothelial carcinoma (UC). PFS will be assessed by measuring the time from the initiation of consolidative therapy to the occurrence of disease progression or death from any cause, whichever comes first. The primary endpoint for this outcome measure is the one-year progression-free survival rate, which represents the proportion of patients remaining free from disease progression or death at 12 months following the treatment. Data collected will provide insight into the efficacy of consolidative therapies in prolonging disease stability and improving survival outcomes for this patient population.

  12 month post-surgery

Secondary Outcomes (5)

• Frequency of Treatment-Related Adverse Events in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma

  Assessed 30 days and 90 days post-surgery

• Frequency of 30-Day Postoperative Complications in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma

  30 days post-surgery

• Changes in EORTC QLQ-C30 Global Health Status / Quality of Life (GHS/QoL) Subscale Scores Pre- and Post-Intervention Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma

  At screening, 30 days post-surgery, 180 days post-surgery then finally at 365 days post-surgery

• Correlation Between Circulating Tumor DNA (ctDNA) Levels and Disease Recurrence Following Local Therapy in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma

  At screening then at 30, 90, 180, 270 and 365 days post-surgery

• Changes in EuroQoL Five Dimensions Five Level (EQ-5D-5L) Scores Pre- and Post-Intervention in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma

  At screening, 30 days post-surgery, 180 days post-surgery then finally at 365 days post-surgery

Study Arms (1)

Radical cystectomy

EXPERIMENTAL

The intervention in this clinical trial consists of definitive surgical management through radical cystectomy with bilateral pelvic lymph node dissection (PLND), urinary diversion, and metastasectomy of surgically resectable or previously radiated metastatic disease. Surgical approach may be either open or robotic, based on surgeon discretion and patient-specific factors. The PLND will be performed in a standard oncologic fashion, including dissection of the common iliac, external iliac, internal iliac, and obturator nodal basins bilaterally. In cases where metastatic lymph nodes are identified beyond these regions, the lymph node dissection may be extended to achieve gross resection of involved nodal disease within the abdomen or retroperitoneum.

Procedure: Radical cystectomy

Interventions

Radical cystectomy PROCEDURE

The intervention in this clinical trial consists of definitive surgical management through radical cystectomy with bilateral pelvic lymph node dissection (PLND), urinary diversion, and metastasectomy of surgically resectable or previously radiated metastatic disease. Surgical approach may be either open or robotic, based on surgeon discretion and patient-specific factors. The PLND will be performed in a standard oncologic fashion, including dissection of the common iliac, external iliac, internal iliac, and obturator nodal basins bilaterally. In cases where metastatic lymph nodes are identified beyond these regions, the lymph node dissection may be extended to achieve gross resection of involved nodal disease within the abdomen or retroperitoneum.

Radical cystectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be at least 18 years of age.
• Have provided informed consent.
• Have ECOG Performance status of 0 or 1.
• 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.
• If applicable, must be a surgical candidate for resection of non-irradiated metastatic lesion(s) at the discretion of the treating surgeon.
• Have adequate organ function as defined by:
• Hgb \>9.0 ng/dL.
• WBC \>3.0 K/mcL.
• PLT \>100 K /mcL.
• AST \<3.0 x ULN U/L.
• ALT \<3.0 x ULN U/L.
• Total Bilirubin \<2.0 x UNL mg/dL.
• Disease characteristics:
• 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.
• If variant histology present, it must be \<50% and UC must be predominant.

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from study entry.
• Received systemic anti-cancer therapy within three weeks prior to the surgery.
• Received radiotherapy within two weeks prior to the surgery.
• Have a positive serum pregnancy test or women who are breastfeeding.
• 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.
• Have any medical condition that, in the treating investigator's opinion, poses an undue risk to the participant's participation in the study.
• Have history of central nervous system (CNS) metastasis and/or leptomeningeal metastasis.

Sponsors & Collaborators

• Yale University: lead
• Medical College of Virginia Foundation: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Interventions

Cystectomy

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Fed Ghali, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Kane

CONTACT

7733696904; laura.kane@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: July 2, 2025
• Study Start: November 26, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)