PTC-guided Neoadjuvant Therapy For Muscle-invasive Bladder Cancer

This study evaluates Patient-derived Tumor-like Cell Clusters (PTC)-guided individualized neoadjuvant therapy in patients with muscle-invasive bladder cancer who are candidates for radical cystectomy.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: PTC guided individualized neoadjuvant therapy

Detailed Description

This is a single-center, open-label, single-arm clinical study evaluating patient-derived tumor-like cell clusters(PTC)-guided individualized neoadjuvant therapy for patients with muscle-invasive bladder cancer (MIBC). Eligible patients will provide fresh tumor tissue for PTC generation and ex vivo drug sensitivity testing. Based on the PTC results, an individualized neoadjuvant regimen will be selected from chemotherapy, antibody-drug conjugates, anti-PD-1 therapy, or their combinations, followed by radical cystectomy and pelvic lymph node dissection. The primary endpoint is pathological complete response (ypT0N0). Secondary and exploratory endpoints include pathological downstaging, progression-free survival, overall survival and treatment-emergent adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rong Yang, M.D.&Ph.D.; Phone Number: +8613851924716; Email: yangr@nju.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
      • Contact: Rong Yang, M.D.&Ph.D.; Phone Number: +8613851924716; Email: yangr@nju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, with clinical stage cT2-4aN0M0.
2. Medically suitable for radical cystectomy as assessed by the multidisciplinary team.
3. Expected survival of at least 18 months.
4. Estimated glomerular filtration rate (eGFR) ≥60 mL/min.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. No prior systemic chemotherapy, immunotherapy, targeted therapy, or antibody-drug conjugate therapy for bladder cancer.
7. Adequate organ and marrow function, including hemoglobin ≥90 g/L, absolute neutrophil count ≥1.5 × 10^9/L, platelet count ≥100 × 10^9/L, potassium 3.5-5.5 mmol/L, ALT and AST ≤1.5 × upper limit of normal, total bilirubin ≤1.5 × upper limit of normal, and left ventricular ejection fraction ≥50%.
8. Ability to understand and willingness to sign written informed consent.
9. Willingness and ability to comply with study procedures and follow-up.
10. Willingness to provide tumor tissue, urine samples, and peripheral blood samples when required for Patient-derived Tumor-like Cell Clusters (PTC) generation, urinary tumor DNA testing, and biomarker analyses.
11. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use medically accepted contraception during study treatment and for 6 months after completion of study treatment. Female participants must not be pregnant or breastfeeding.

Exclusion Criteria:

1. Non-urothelial carcinoma histology, or mixed histology with a predominant non-urothelial component, such as small cell carcinoma or adenocarcinoma.
2. Evidence of distant metastatic disease on imaging.
3. Uncontrolled or clinically significant comorbid illness, including but not limited to uncontrolled infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, clinically significant arrhythmia, interstitial lung disease, severe chronic gastrointestinal disease associated with diarrhea, or psychiatric/social conditions that may limit compliance or increase study risk.
4. Known hypersensitivity or allergy to any study treatment, or history of autoimmune disease.
5. Prior exposure to systemic immunotherapy or antibody-drug conjugate therapy, including but not limited to anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies.
6. Receipt of a live attenuated vaccine or occurrence of severe infection within 1 month before enrollment.
7. Use of systemic corticosteroids or other systemic immunosuppressive therapy within 2 weeks before enrollment, or expected need for systemic immunosuppressive therapy during the study.
8. Active or symptomatic viral hepatitis or other chronic liver disease, or known human immunodeficiency virus infection.
9. Active tuberculosis.
10. Any other condition that, in the opinion of the investigator, makes the participant unsuitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental Group

Drug: PTC guided individualized neoadjuvant therapy; Fresh tumor tissue will be collected before neoadjuvant treatment to generate Patient-derived Tumor-like Cell Clusters (PTC) for ex vivo drug sensitivity testing. Based on the PTC results, each participant will receive an individualized neoadjuvant regimen selected from gemcitabine plus cisplatin, disitamab vedotin (RC48), enfortumab vedotin, toripalimab, or their protocol-defined combinations. Treatment will be administered for up to 4 cycles before radical cystectomy and pelvic lymph node dissection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	Pathological complete response is defined as the proportion of participants with no residual viable tumor in the bladder and no pathological lymph node involvement, defined as ypT0N0, based on pathological assessment of surgical specimens obtained after radical cystectomy and pelvic lymph node dissection.	immediately evaluated after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Downstaging (pDS) Rate	Pathological downstaging is defined as the proportion of participants with pathological stage lower than ypT2N0, including ypT0N0, based on surgical pathology after radical cystectomy and pelvic lymph node dissection.	immediately evaluated after surgery
Progression-Free Survival (PFS)	Progression-free survival is defined as the time from enrollment to disease progression or death from any cause, whichever occurs first.	From enrollment until disease progression or death, assessed up to 3 years.
Overall Survival (OS)	Overall survival is defined as the time from enrollment to death from any cause.	From enrollment until death from any cause, assessed up to 3 years.
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Treatment-emergent adverse events are defined as adverse events occurring after initiation of study treatment, assessed according to CTCAE version 5.0.	From the first dose of neoadjuvant therapy until the end of safety follow-up, assessed up to 6 months after enrollment.

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: July 1, 2026
• First Submitted That Met QC Criteria: July 1, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: 2025-0620-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No