A Prospective, Multicenter, Randomized Controlled Study of Disitamab Vedotin Plus Toripalimab With or Without Pelvic Lymph Node Dissection for Bladder-Sparing Treatment in Patients With cT2-3N0M0 Bladder Urothelial Carcinoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 114
- Locations
- 1
- Primary Endpoint
- 2-year Bladder-intact Event-free Survival Rate
Study Overview
Brief Summary
This is a prospective, multicenter, randomized controlled superiority study designed to evaluate whether the addition of pelvic lymph node dissection improves bladder-intact event-free survival in patients with cT2-3N0M0 bladder urothelial carcinoma receiving bladder-sparing treatment. Eligible patients with HER2 expression of IHC 2+ or higher who decline radical cystectomy will be randomized 1:1 to receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab with or without standardized pelvic lymph node dissection. The primary endpoint is the 2-year bladder-intact event-free survival rate. Secondary endpoints include clinical complete response, partial response, disease progression, overall survival, quality of life, safety, treatment cost, and exploratory biomarker analyses.
Detailed Description
Muscle-invasive bladder cancer is commonly treated with radical cystectomy; however, bladder-sparing strategies are needed for selected patients who decline cystectomy. This study evaluates a bladder-sparing strategy based on maximal transurethral resection of bladder tumor, disitamab vedotin plus toripalimab, and the addition of standardized pelvic lymph node dissection.
Participants will be randomized to receive disitamab vedotin plus toripalimab with or without pelvic lymph node dissection after maximal transurethral resection of bladder tumor. Tumor response will be assessed by imaging, cystoscopy or transurethral resection/biopsy when clinically indicated, and urine cytology. Participants who meet bladder-sparing criteria will enter bladder-intact follow-up according to the protocol. Safety, survival, quality of life, treatment cost, and exploratory biomarkers will also be evaluated.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female participants aged 18 years or older.
- •Histologically confirmed bladder urothelial carcinoma.
- •Clinical stage cT2-3N0M0 according to the AJCC 8th edition TNM staging system.
- •HER2 expression of IHC 2+ or higher.
- •Participants who decline radical cystectomy as assessed by the investigator.
- •Adequate organ function as defined in the study protocol.
- •Ability to understand and willingness to sign written informed consent.
Exclusion Criteria
- •Known allergy or hypersensitivity to disitamab vedotin, toripalimab, their excipients, or other monoclonal antibodies.
- •Prior radiotherapy for bladder cancer.
- •Prior anticancer treatment that may affect efficacy assessment, as defined in the study protocol.
- •Pregnant or breastfeeding women.
- •Any serious uncontrolled disease or medical condition that, in the investigator's judgment, would make participation inappropriate.
- •Participation in another interventional clinical trial that may interfere with this study.
Arms & Interventions
Disitamab Vedotin Plus Toripalimab With Pelvic Lymph Node Dissection
Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab and standardized pelvic lymph node dissection.
Intervention: Toripalimab (Drug)
Disitamab Vedotin Plus Toripalimab With Pelvic Lymph Node Dissection
Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab and standardized pelvic lymph node dissection.
Intervention: Disitamab Vedotin (RC48) (Drug)
Disitamab Vedotin Plus Toripalimab With Pelvic Lymph Node Dissection
Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab and standardized pelvic lymph node dissection.
Intervention: Transurethral Resection of Bladder Tumor (Procedure)
Disitamab Vedotin Plus Toripalimab With Pelvic Lymph Node Dissection
Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab and standardized pelvic lymph node dissection.
Intervention: Pelvic Lymph Node Dissection (Procedure)
Disitamab Vedotin Plus Toripalimab Without Pelvic Lymph Node Dissection
Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab without planned pelvic lymph node dissection.
Intervention: Disitamab Vedotin (RC48) (Drug)
Disitamab Vedotin Plus Toripalimab Without Pelvic Lymph Node Dissection
Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab without planned pelvic lymph node dissection.
Intervention: Transurethral Resection of Bladder Tumor (Procedure)
Disitamab Vedotin Plus Toripalimab Without Pelvic Lymph Node Dissection
Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab without planned pelvic lymph node dissection.
Intervention: Toripalimab (Drug)
Outcomes
Primary Outcomes
2-year Bladder-intact Event-free Survival Rate
Time Frame: 24 months after randomization
The proportion of participants who remain alive with an intact bladder and without muscle-invasive bladder cancer recurrence, regional lymph node recurrence, distant metastasis, radical cystectomy, or bladder cancer-related death at 24 months after randomization.
Secondary Outcomes
- Clinical Complete Response Rate(After completion of induction treatment, up to 12 weeks)
- Partial Response Rate(After completion of induction treatment, up to 12 weeks)
- Disease Progression Rate(Up to 24 months after randomization)
- Overall Survival(Up to 60 months after randomization)
- Incidence and Severity of Adverse Events(From the first dose through 30 days after the last dose, up to approximately 19 months)
- Quality of Life Score(Baseline to 24 months after randomization)
- Total Treatment Cost(From randomization to the end of follow-up, up to 60 months)