Bladder Cancer
Conditions
Brief summary
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.
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.
Interventions
DRUGPTC 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.
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | immediately evaluated after surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Downstaging (pDS) Rate | immediately evaluated after surgery | 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. |
| Progression-Free Survival (PFS) | From enrollment until disease progression or death, assessed up to 3 years. | Progression-free survival is defined as the time from enrollment to disease progression or death from any cause, whichever occurs first. |
| Overall Survival (OS) | From enrollment until death from any cause, assessed up to 3 years. | Overall survival is defined as the time from enrollment to death from any cause. |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From the first dose of neoadjuvant therapy until the end of safety follow-up, assessed up to 6 months after enrollment. | Treatment-emergent adverse events are defined as adverse events occurring after initiation of study treatment, assessed according to CTCAE version 5.0. |
Countries
China
Contacts
CONTACTRong Yang, M.D.&Ph.D.
Outcome results
None listed