A Prospective, Single Center Clinical Study to Examine Cisplatin-based Chemotherapy Combined With Tislelizumab as Bladder Sparing Treatment for Patients With Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Clinical complete remission rate (cCR)
研究概览
简要总结
This study is designed prospectively to investigate the safety, efficacy and feasibility of cisplatin-based chemotherapy combined with tislelizumab as bladder sparing treatment for patients with muscle invasive bladder cancer (MIBC) which are eligible for cisplatin. The patients that achieved clinical remission after 4 cycles of cisplatin/gemcitabine and tislelizumab, will receive tislelizumab maintenance therapy for a year or 13 cycles. Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The safety, tolerability, and efficacy of tislelizumab in patients with PD-L1 positive urothelial carcinoma who progressed during/following platinum-containing therapy was proved in a phase 2 trial (CTR20170071).
This trial investigates the efficacy of cisplatin-based chemotherapy combined with Tislelizumab to induce clinical complete remission of muscle invasive bladder cancer and the feasibility to provide bladder sparing treatment for these patients.
详细描述
The patients that meet the Inclusion and Exclusion Criteria will treat with 4 cycles of cisplatin-based chemotherapy combined with Tislelizumab (200mg per cycle) prior to cystectomy discussion. The patients that show clinical benefit will receive tislelizumab for bladder sparing. Forty patients will be enrolled in this trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 and ≤75 years old on day of signing informed consent
- •Signing informed consent
- •Patients with histologically confirmed muscle-invasive bladder cancer (cT2-T4, N0, M0) and with strong intent to bladder sparing(Patients with mixed histology, predominantly transitional cells, could be enrolled. )
- •Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 15 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available.
- •ECOG performance status of 0 or 1
- •Adequate organ and marrow function for cisplatin treatment
- •No received prior therapy with systemic chemotherapy or immunotherapy
排除标准
- •Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Any approved anticancer therapy within 28 days before enrollment
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- •Participants with uncontrolled hypercalcemia
- •Participants with active autoimmune diseases or history of autoimmune diseases that may relapse
- •History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases
- •A known history of HIV infection
- •Prior allogeneic stem cell transplantation or organ transplantation
- •History of severe hypersensitivity reactions to other monoclonal antibodies
- •History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds
研究组 & 干预措施
Arm 1
Patients will receive 4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before cystectomy discussion. The patients reach clinical complete remission will receive tislelizumab maintenance therapy for a year or 13 cycles.
干预措施: Tislelizumab (Drug)
Arm 1
Patients will receive 4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before cystectomy discussion. The patients reach clinical complete remission will receive tislelizumab maintenance therapy for a year or 13 cycles.
干预措施: Cisplatin (Drug)
Arm 1
Patients will receive 4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before cystectomy discussion. The patients reach clinical complete remission will receive tislelizumab maintenance therapy for a year or 13 cycles.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Clinical complete remission rate (cCR)
时间窗: Up to 24 months
The clinical complete remission rate (cCR) was defined as the proportion of patients with clinically confirmed cT0 or cTa(AJCC Cancer Staging Manual,8th ed. 2017 edition ).The cT0 or cTa was assessed by cystoscopy examination at 12 weeks after the initiation of combination therapy. Two-sided Clopper-Pearson 95% confidence intervals were constructed to evaluate the accuracy of cCR.
次要结局
- Duration of cCR(Up to 24 months)
- Bladder-intact event-free survival (BI-EFS)(Up to 24 months)