Is Prolonged Systemic Immunotherapy Necessary After Achieving Tumor-free Status in Patients With Extensive Transurethrally Unresectable Very-high-risk NMIBC?

NCT07625527 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: Truce-LB03
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 4

Brief Summary

Patients with extensive transurethrally unresectable very-high-risk non-muscle-invasive bladder cancer (NMIBC) may achieve a tumor-free status after systemic immunotherapy-based bladder-sparing treatment combined with transurethral resection of bladder tumor (TURBT). However, the optimal duration of systemic immunotherapy after achieving a tumor-free status remains uncertain. Prolonged treatment may increase toxicity, treatment burden, and cost, while some patients may maintain durable disease control without continued therapy. This randomized study aims to evaluate whether active surveillance after achieving tumor-free status is a feasible alternative to continued systemic immunotherapy in patients with extensive transurethrally unresectable very-high-risk NMIBC. Patients will initially receive systemic immunotherapy-based treatment followed by disease evaluation using cystoscopy with biopsy and/or TURBT, urine cytology, urinary tumor DNA (utDNA), and imaging assessments. Patients who achieve tumor-free status after treatment and complete resection of visible disease will be randomized to either active surveillance or continued systemic immunotherapy. The study will evaluate recurrence outcomes, bladder preservation, progression, safety, and patient management strategies following achievement of tumor-free status. The trial also aims to explore the role of urinary tumor DNA in identifying patients who may safely undergo treatment de-escalation and active surveillance.

Conditions

Bladder (Urothelial, Transitional Cell) Cancer; Non Muscle Invasive Bladder Cancer

Keywords

Non-muscle-invasive bladder cancer (NMIBC); Liquid biopsy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Bladder-intact event-free survival (BI-EFS)

  Time from randomization to the first occurrence of high-risk NMIBC recurrence, progression to muscle-invasive bladder cancer, distant metastasis, radical cystectomy, or death from any cause.

  Up to 2 years from randomization

Secondary Outcomes (5)

• Recurrence-free survival (RFS)

  Up to 2 years from randomization

• Progression-free survival (PFS)

  Up to 2 years from randomization

• Radical cystectomy-free survival (RCFS)

  Up to 2 years from randomization

• Overall survival (OS)

  Up to 2 years from randomization

• Incidence of treatment-related adverse events

  Up to 2 years from randomization

Other Outcomes (6)

• Recurrence-Free Survival According to Urinary Tumor DNA Status

  Up to 2 years from randomization

• utDNA conversion during surveillance

  Up to 2 years from initial systemic administration

• Bladder-Intact Event-Free Survival According to Response Cohort in the Active Surveillance Arm

  Up to 2 years from randomization

Study Arms (4)

Arm A-1 (Cohort A Active Surveillance)

EXPERIMENTAL

Patients in Cohort A who achieve early tumor-free status after initial systemic immunotherapy-based treatment will undergo active surveillance with protocol-defined cystoscopy, urine cytology, urinary tumor DNA testing, biopsy as clinically indicated, and imaging assessments.

Behavioral: Active Surveillance

Arm A-2 (Cohort A Continued Systemic Immunotherapy)

ACTIVE COMPARATOR

Patients in Cohort A who achieve early tumor-free status after initial systemic immunotherapy-based treatment will continue systemic immunotherapy for a protocol-defined duration with ongoing disease surveillance.

Drug: PD-1/PD-L1 Inhibitor-Based Systemic Immunotherapy

Arm B-1 (Cohort B Active Surveillance)

EXPERIMENTAL

Patients in Cohort B who do not achieve tumor-free status at initial evaluation but subsequently achieve tumor-free status after complete TURBT/resection and additional systemic immunotherapy will undergo active surveillance with protocol-defined surveillance assessments.

Behavioral: Active Surveillance

Arm B-2 (Cohort B Continued Systemic Immunotherapy)

ACTIVE COMPARATOR

Patients in Cohort B who subsequently achieve tumor-free status after complete TURBT/resection and additional systemic immunotherapy will continue systemic immunotherapy for a protocol-defined duration with ongoing disease surveillance.

Drug: PD-1/PD-L1 Inhibitor-Based Systemic Immunotherapy

Interventions

Active Surveillance BEHAVIORAL

Patients undergo protocol-defined surveillance after achieving tumor-free status, including cystoscopy, biopsy as clinically indicated, urine cytology, urinary tumor DNA testing, and imaging assessments, without continued systemic PD-1/PD-L1 inhibitor therapy unless disease recurrence or progression occurs.

Arm A-1 (Cohort A Active Surveillance); Arm B-1 (Cohort B Active Surveillance)

PD-1/PD-L1 Inhibitor-Based Systemic Immunotherapy DRUG

Patients continue protocol-defined systemic PD-1/PD-L1 inhibitor therapy after achieving tumor-free status for up to approximately 1 year, with ongoing surveillance including cystoscopy, urine cytology, urinary tumor DNA testing, and imaging assessments.

Arm A-2 (Cohort A Continued Systemic Immunotherapy); Arm B-2 (Cohort B Continued Systemic Immunotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically confirmed very-high-risk non-muscle-invasive urothelial carcinoma of the bladder.
• Has transurethrally unresectable bladder tumor, defined as visually incomplete TURBT and/or extensive high-volume disease considered unsuitable for complete and oncologically adequate transurethral resection.
• Has undergone cystoscopy and TURBT evaluation before study enrollment.
• Has received systemic PD-1/PD-L1 inhibitor-based bladder-sparing therapy before randomization.
• Has achieved tumor-free status before randomization, defined as:
• No visible bladder tumor on cystoscopy;
• Negative bladder biopsy and/or TURBT pathology;
• Negative urine cytology;
• Negative urinary tumor DNA (utDNA);
• No radiographic evidence of progression or metastasis.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Has adequate organ function.
• Has provided written informed consent.
• Cohort A Only
• Achieved tumor-free status at the initial response evaluation after induction systemic therapy.

You may not qualify if:

• Has muscle-invasive bladder cancer (≥T2), locally advanced unresectable disease, nodal disease, or distant metastasis.
• Has concurrent upper tract urothelial carcinoma.
• Has persistent visible tumor, positive bladder pathology, positive urine cytology, or positive utDNA before randomization.
• Has received prior systemic immunotherapy for metastatic urothelial carcinoma.
• Has active autoimmune disease requiring systemic treatment.
• Is receiving systemic immunosuppressive therapy.
• Has uncontrolled infection requiring systemic therapy.
• Has another active malignancy requiring systemic treatment.
• Has known active hepatitis B, hepatitis C, human immunodeficiency virus infection, or active tuberculosis.
• Has pregnancy or breastfeeding.
• Has any medical or psychiatric condition that, in the investigator's judgment, would interfere with study participation or interpretation of results.

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (4)

The Second Hospital of Tianjin Medical University

Tianjin, 300000, China

Location

General Hospital of Tianjin Medical University

Tianjin, China

Location

Tianjin Hospital

Tianjin, China

Location

Xingtai People's Hospital

Xingtai, China

Location

MeSH Terms

Conditions

Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Hailong Hu, MD

  Department of Urology, The Second Hospital of Tianjin Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hailong Hu, MD

CONTACT

+8619801518556; huhailong@tmu.edu.cn

Yunkai Qie, MD

CONTACT

qieyunkai@tmu.edu.cn

Study Design

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

Model Details: Patients with extensive transurethrally unresectable very-high-risk non-muscle-invasive bladder cancer will initially receive systemic PD-1/PD-L1 immunotherapy-based bladder-sparing treatment followed by disease evaluation. Patients achieving tumor-free status after treatment, TURBT, and/or complete resection of visible disease will be randomized in parallel to active surveillance or continued systemic immunotherapy. Randomization will occur within two predefined cohorts based on response status at initial disease evaluation.

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: June 4, 2026
• Study Start: May 30, 2026
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): May 30, 2032
• Last Updated: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

CN (4)