PD-1 Antibody for the Prevention of Adenomatous Polyps and Second Primary Tumors in Patients With Lynch Syndrome: An Open-label, Multicenter, Randomized Controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- The percentage of patients from randomization to the first appearance of one of the following: adenomatous polyps or second primary tumors
研究概览
简要总结
This study aims to explore the role of PD-1 Antibody in preventing adenomatous polyps and second primary tumors in patients with Lynch Syndrome. There two arms, one is the experimental arm (PD-1 antibody prevention group) and the other is the control arm (routine follow-up group). For the experimental group, Tripleitriumab (PD-1 antibody) is given every 3 months for a year.
详细描述
Lynch syndrome (LS) is a hereditary cancer syndrome that causes the majority of hereditary CRC and approximately 3% of all CRC. LS significantly increases the risk for an individual to develop CRC during their lifetime. Individuals with LS also have an increased risk to develop extracolonic cancers, including endometrial, gastric, ovarian, upper urinary tract, small bowel, biliary tract, CNS, and certain types of skin cancer. Given the hereditary nature of this syndrome, preventing second primary tumors in patients with Lynch Syndrome after surgery to the primary site is very important.
The purpose of this study is to prevent adenomatous polyps and second primary tumors using PD-1 antibody (Tripleitriumab) in patients with Lynch Syndrome.
The primary outcome of this study is the incidence of intestinal adenomatous polyps and secondary primary tumors. The secondary outcomes are the incidence of colorectal adenomatous polyps greater than 1cm, incidence of high-grade colorectal polyps, treatment-related adverse events, disease-free Survival and overall Survival.
There are two groups: the PD-1 antibody prevention group and the routine follow-up group. For the PD-1 antibody prevention group, participants will receive Toripalimab 240mg IV every 3 months for a year. For the routine follow-up group, there is no drug intervention.
This whole study will take 5 years: the first year for recruiting and the latter four years for follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Lynch syndrome with germline variants of MLH1, MSH2, or EPCAM (pathogenic or likely pathogenic variants)
- •Necessary treatments have been done, such as surgery, chemotherapy, radiation therapy, etc.
- •Have a resection, including right hemicolectomy, left hemicolectomy, sigmoid colectomy, or anterior resection of rectal cancer, or endoscopic adenoma resection
- •Aged 18-70 years old
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
- •White blood cell (WBC) > 4000/mm3, Platelet count >100000/mm3, HB >10 g/dL
- •Serum glutamic-oxaloacetic transaminase (SGOT) < 1.5 × the upper limit of normal (ULN), Serum glutamic pyruvic transaminase (SGPT) < 1.5 × ULN prior to randomization, Total bilirubin (TBIL) < 1.5 mg/dL
- •Serum creatinine (Scr) <1.8 mg/dL
排除标准
- •Lynch syndrome with germline variants of MSH6 and PMS2
- •Previous immunotherapy has been taken, such as anti-PD-1, anti-PD-L1, etc.
- •Long-term use of aspirin
- •Suffering from autoimmune diseases
- •Active infection with hepatitis B or hepatitis C (high copy number of viral DNA) or human immunodeficiency virus (HIV)
- •Other clinically serious active infections (NCI-CTC 4.0)
- •With cachexia or organ dysfunction
- •Suffering from seizures requiring treatment (such as steroids or antiepileptic therapy)
- •Unable to participate or complete the study due to substance abuse, or medical, psychological, or social disorder
- •Known allergy to any drugs in this study
- •Pregnant or nursing women, or women of childbearing potential who are not using adequate contraception
- •Any unstable condition or situation that could compromise the safety and compliance of participants.
- •Failure to sign an informed consent form
研究组 & 干预措施
Prevention group
Toripalimab: 240mg IV every 3 months for a year
干预措施: PD-1 Antibody (Drug)
结局指标
主要结局
The percentage of patients from randomization to the first appearance of one of the following: adenomatous polyps or second primary tumors
时间窗: up to 5 years
次要结局
- The percentage of patients developing high-grade polyps on pathology within 5 years from randomization.(up to 5 years)
- The percentage of patients developing polyps greater than 1cm within 5 years from randomization(up to 5 years)
- Treatment-related adverse events(up to 5 years)
- Effectiveness with different genotypes or phenotypes(up to 5 years)
- Disease-free Survival(up to 5 years)
- Overall Survival(up to 5 years)
研究者
Pei-Rong Ding
Professor
Sun Yat-sen University