PTC-guided Neoadjuvant Therapy For Muscle-invasive Bladder Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, with clinical stage cT2-4aN0M
- •Medically suitable for radical cystectomy as assessed by the multidisciplinary team.
- •Expected survival of at least 18 months.
- •Estimated glomerular filtration rate (eGFR) ≥60 mL/min.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •No prior systemic chemotherapy, immunotherapy, targeted therapy, or antibody-drug conjugate therapy for bladder cancer.
- •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%.
- •Ability to understand and willingness to sign written informed consent.
- •Willingness and ability to comply with study procedures and follow-up.
- •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.
- •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.
排除标准
- •Non-urothelial carcinoma histology, or mixed histology with a predominant non-urothelial component, such as small cell carcinoma or adenocarcinoma.
- •Evidence of distant metastatic disease on imaging.
- •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.
- •Known hypersensitivity or allergy to any study treatment, or history of autoimmune disease.
- •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.
- •Receipt of a live attenuated vaccine or occurrence of severe infection within 1 month before enrollment.
- •Use of systemic corticosteroids or other systemic immunosuppressive therapy within 2 weeks before enrollment, or expected need for systemic immunosuppressive therapy during the study.
- •Active or symptomatic viral hepatitis or other chronic liver disease, or known human immunodeficiency virus infection.
- •Active tuberculosis.
- •Any other condition that, in the opinion of the investigator, makes the participant unsuitable for this study.
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: 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.
次要结局
- Pathological Downstaging (pDS) Rate(immediately evaluated after surgery)
- Progression-Free Survival (PFS)(From enrollment until disease progression or death, assessed up to 3 years.)
- Overall Survival (OS)(From enrollment until death from any cause, assessed up to 3 years.)
- 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.)