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

Official title

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

Overview

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.

Detailed description

This is a single-arm, open-label, phase 2 clinical trial designed to evaluate the impact of consolidative local therapy in participants with locally advanced/oligo-metastatic urothelial carcinoma (UC) who have demonstrated stable or responsive disease to first-line systemic therapy.

Interventions

• Procedure Radical cystectomy
  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, interna

Primary outcome measures

• 12-Month Progression-Free Survival in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma [Time frame: 12 month post-surgery]

Secondary outcome measures (5)

• Frequency of Treatment-Related Adverse Events in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma [Time frame: Assessed 30 days and 90 days post-surgery]
• Frequency of 30-Day Postoperative Complications in Patients with Locally Advanced/Oligo-Metastatic Urothelial Carcinoma [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: At screening, 30 days post-surgery, 180 days post-surgery then finally at 365 days post-surgery]

Eligibility criteria

Inclusion criteria

• 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.
• 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.
• 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.

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Yale University — New Haven

Identifiers

NCT: NCT07048457 · 2000039076

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗