Phase II Study of Neoadjuvant Toripalimab with Gemcitabine-Cisplatin in Subjects with T2-4aN0M0 Bladder Cancer: GZZJU-2021NB
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Pathological response rate evaluated after 4 cycles of neoadjuvant Toripalimab in combination with gemcitabine and cisplatin at time of radical cystectomy, each cycle is 21 days
研究概览
简要总结
This is a pre-surgical study involving subjects with local advanced bladder cancer, who are candidates for neoadjuvant therapy. It is a single-arm phase II portion.
详细描述
Outline: This study is a single-arm, open, exploratory clinical trial;
Subjects receive: gemcitabine 1000mg/m2 IV Day1 and Day8 every 21 days repeated for 4 cycles; cisplatin 35mg/m2 IV Day1 and Day2 every 21 days, repeated for 4 cycles.
Toripalimab at recommended phase II dose is given every 3 weeks for 4 doses starting with Cycle1 Day1(C1D1).
Subjects will then have surgery to remove their primary tumor within 6 weeks after their last dose of neoadjuvant therapy.
Eastern Cooperative Oncology Group (ECOG) performance status: 0-1
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
- •Patients between 18 and 75 years old on day of signing informed consent, regardless of gender;
- •ECOG score 0-1 points, expected survival time> 6 months;
- •Pathologically confirmed locally advanced bladder urothelial carcinoma (cT2-T4a, N≤1, M0, tumor staging according to American Joint Committee on Cancer (AJCC), 2017, eighth edition);
- •Appropriate and plan for radical cystectomy;
- •According to the RECIST1.1 standard, there is at least one measurable lesion (spiral CT scan ≥10mm);
- •Since the diagnosis of locally advanced bladder urothelial carcinoma, patient has not received anti-tumor system treatment;
- •The main organ functions are normal, and the following requirements must be met within 2 weeks before the first study treatment:
- •Routine blood examination must meet: WBC≥4.0×109/L; PLT≥90×109/L; Hb≥90g/L (patients can be infused with red blood cells to meet this standard);
- •Blood biochemical examination must meet: serum creatinine (Cr) ≤1.5 times the upper limit of normal (ULN) or endogenous creatinine clearance ≥60mL/min; TBIL≤1.5×ULN; ALB≥30g/L; ALT and AST≤ 3.0×ULN; TSH≤1.5×ULN.
- •Female patients with fertility must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and they voluntarily adopt appropriate methods of contraception during the observation period and within 8 weeks after the last administration;
- •Agree to provide diagnosis and treatment-related tumor tissue specimens for clinical research, and have the ability to follow the planned research visit until the clinical recurrence/progress is clear.
- •Sign informed consent voluntarily.
排除标准
- •Have previously received anti-PD1/PDL1/CTLA-4 antibody treatment or systemic chemotherapy, bladder infusion chemotherapy is excluded;
- •Have received bladder bacille Calmette Guerin (BCG) infusion therapy within 4 weeks;
- •Have received radiotherapy of the bladder in the past;
- •Patients with any history of active autoimmune disease or autoimmune disease;
- •Complicated diseases that require the use of immunosuppressive drugs; concurrent diseases that require the use of immunosuppressive agents for systemic or locally absorbable corticosteroids. It is forbidden to use prednisone greater than 10 mg/day or the same dose in the 2 weeks before the use of the study drug;
- •Combined with other malignant tumors;
- •Have a history of allergy to other antibody drugs;
- •The history of human immunodeficiency virus (HIV) infection;
- •The subject has active infection, including active tuberculosis;
- •Combined with severe heart disease, or combined with New York Heart Association (NYHA) grade 3 or 4 cardiac insufficiency;
- •Kidney transplant patients;
研究组 & 干预措施
Toripalimab+Gemcitabine/Cisplantin（GC）
Subjects receive gemcitabine/cisplatin every 21 days, repeated for 4 cycles. . Toripalimab is given every 21 days for 4 doses starting C1D1. Subjects will then have consolidative surgery to remove their primary tumor within 6 weeks after their last dose of neoadjuvant therapy.
干预措施: Neoadjuvant Toripalimab in Combination With Gemcitabine and Cisplatin (Drug)
结局指标
主要结局
Pathological response rate evaluated after 4 cycles of neoadjuvant Toripalimab in combination with gemcitabine and cisplatin at time of radical cystectomy, each cycle is 21 days
时间窗: Up to 90 days after last dose of investigation product
the absence of residual muscle invasive bladder cancer in surgical specimens of cystectomy (pathologically decreased to ≤pT1N0, including pT0, pT1, pTa and pTis
次要结局
- Tumor immune microenvironment indicators assessed by Microenvironment Analysis Panel(Assessed lasted for 24 months, calculated from the date of enrolled)
- Safety assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4 criteria(From the first day of the treatment to the end of neoadjuvant treatment, assessed up to 6 month)
- Progression-free survival assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1(From the start of neoadjuvant therapy to the time when any disease progression is first recorded. Assessed lasted for 24 months, calculated from the date of enrolled)
研究者
Abai Xu
Vice Director
Zhujiang Hospital