ChiCTR2500101259 版本V1.0 版本创建时间2025/04/22 17:13:07 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2500101259 

最近更新日期：

Date of Last Refreshed on：

2025-04-22 17:13:01 

注册时间：

Date of Registration：

2025-04-22 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

替雷利珠单抗联合贝伐单抗及SOX方案化疗一线治疗胃癌肝转移的有效性和安全性临床研究

Public title：

Efficacy and safety of tislelizumab combined with bevacizumab and SOX chemotherapy as first-line treatment for gastric cancer with liver metastasis

注册题目简写：

English Acronym：

研究课题的正式科学名称：

替雷利珠单抗联合贝伐单抗及SOX方案化疗一线治疗胃癌肝转移的有效性和安全性临床研究

Scientific title：

Efficacy and safety of tislelizumab combined with bevacizumab and SOX chemotherapy as first-line treatment for gastric cancer with liver metastasis

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

陆晟 

研究负责人：

严超 

Applicant：

Sheng Lu 

Study leader：

Chao Yan 

申请注册联系人电话：

Applicant telephone：

+86 156 1880 2776

研究负责人电话：

Study leader's telephone：

+86 136 8174 9682

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

lusheng@vip.126.com

研究负责人电子邮件：

Study leader's E-mail：

yanchaosuper@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

上海市黄浦区瑞金二路197号

研究负责人通讯地址：

上海市黄浦区瑞金二路197号

Applicant address：

No. 197, Ruijin 2nd Road, Huangpu District, Shanghai

Study leader's address：

No. 197, Ruijin 2nd Road, Huangpu District, Shanghai

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

上海交通大学医学院附属瑞金医院

Applicant's institution：

Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine

研究负责人所在单位：

上海交通大学医学院附属瑞金医院

Affiliation of the Leader：

Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

(2025)临伦审第(179)号

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

瑞金医院涉及人体的临床与科研项目伦理委员会

Name of the ethic committee：

Ruijin Hospital Ethics Committe

伦理委员会批准日期：

Date of approved by ethic committee：

2025-04-03 00:00:00

伦理委员会联系人：

赵彦琳

Contact Name of the ethic committee：

Yanlin Zhao

伦理委员会联系地址：

上海市黄浦区瑞金二路197号

Contact Address of the ethic committee：

No. 197, Ruijin 2nd Road, Huangpu District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 80585870

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

上海交通大学医学院附属瑞金医院

Primary sponsor：

Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine

研究实施负责（组长）单位地址：

上海市黄浦区瑞金二路197号

Primary sponsor's address：

No. 197, Ruijin 2nd Road, Huangpu District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海交通大学医学院附属瑞金医院

具体地址：

上海市黄浦区瑞金二路197号

Institution
hospital：

Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Address：

No. 197, Ruijin 2nd Road, Huangpu District, Shanghai

经费或物资来源：

自筹

Source(s) of funding：

Self-raised

Target disease：

Gastric cancer with liver metastasis

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 II期临床试验 

Study phase：

2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

主要研究目的：评价替雷利珠单抗联合贝伐单抗及SOX方案一线治疗胃癌肝转移患者的客观缓解率（ORR）。 次要研究目的：评价疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和R0切除率；评价治疗的安全性和耐受性，包括NCI-CTCAE 5.0版定义的不良事件（AE）和严重不良事件（SAE）以及CSCO免疫检查点抑制剂相关毒性管理指南2023版定义的免疫相关不良事件（irAE）。  

Objectives of Study：

Main objective: To evaluate the objective response rate (ORR) of tislelizumab combined with bevacizumab and SOX chemotherapy as the first-line treatment for gastric cancer with liver metastasis. Secondary objectives: To evaluate disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and R0 resection rate; to assess the safety and tolerability of the treatment, including adverse events (AE) and serious adverse events (SAE) as defined by the NCI-CTCAE 5.0 version and immune-related adverse events (irAE) as defined by the CSCO Immune Checkpoint Inhibitor-related Toxicity Management Guidelines 2023 edition.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.签署书面的知情同意书，依从性良好，并且理解和遵循研究的要求； 2.年龄18～75岁； 3.经组织学和/或细胞学确诊的胃或GEJ腺癌； 4.影像学评估存在明确可测量（符合RECIST 1.1标准）的肝转移病灶； 5.除肝转移外，临床上无其他远处转移征象； 6.腹腔镜探查排除腹膜转移（P0/CY0）； 7.既往未接受过针对晚期转移性胃癌的系统性治疗； 8.美国东部肿瘤合作组体力状况评分（ECOG PS）为0或1分； 9.无胃肠道梗阻、穿孔及出血； 10.在研究药物首次给药前<=7天，器官功能良好，如以下实验室检查值所示： a.患者在筛选期血样采集前<=14天内未接受血液、血小板输注或生长因子支持治疗，且需满足： ANC>=1.5×10^9/L； 血小板>=100×10^9/L； 血红蛋白>=90g/L； b.血清肌酐<=1.5倍正常值上限（ULN）； c.AST和ALT<=2.5倍ULN； d.血清总胆红素<=1.5倍ULN； e.国际标准化比值（INR）<=1.5或凝血酶原时间<=1.5倍ULN； f.活化部分凝血活酶时间（aPTT）<=1.5倍ULN； g.血清白蛋白>=30g/L； 11.非活动性/无症状的携带者、慢性或活动性HBV感染患者需要满足下述标准：在筛选期HBV DNA＜500 IU/mL（or 2500 copies/mL）。筛选期已经治愈的HCV感染的患者可以入组; 12.有妊娠能力的女性受试者必须在首次用药前72小时内进行血清妊娠试验，且结果为阴性，并且愿意在试验期间和末次给药后120天采用高效方法避孕。对于伴侣为育龄妇女的男性受试者，应为手术绝育或同意在试验期间和末次给药后120天采用高效方法避孕。

Inclusion criteria

1. Signed written informed consent, good compliance, and understand and follow the requirements of the study; 2. Age 18~75 years old; 3. Histologically and/or cytologically confirmed gastric or GEJ adenocarcinoma; 4. Presence of clear and measurable (in line with RECIST 1.1 criteria) liver metastases on imaging evaluation; 5. Except for liver metastasis, there are no other clinical signs of distant metastasis; 6. Laparoscopic exploration to exclude peritoneal metastasis (P0/CY0); 7. Have not received prior systemic therapy for advanced metastatic gastric cancer; 8. Eastern Cooperative Oncology Group Performance Status Score (ECOG PS) of 0 or 1; 9. No gastrointestinal obstruction, perforation and bleeding; 10. Good organ function prior to <=7 days prior to the first dose of study drug, as indicated by the following laboratory test values: a. Patients have not received blood, platelet transfusion, or growth factor supportive therapy within <=14 days prior to blood sample collection during the screening period, and must meet: ANC>=1.5×10^9/L; Platelet >=100×10^9/L; hemoglobin > = 90 g/L; b. Serum creatinine < = 1.5 times the upper limit of normal (ULN); c. AST and ALT < = 2.5 times ULN; d. Serum total bilirubin < = 1.5 times ULN; International normalized ratio (INR) < = 1.5 or prothrombin time < = 1.5 times ULN; f. Activated partial thromboplastin time (aPTT) < = 1.5 times ULN; g. Serum albumin>=30g/L; 11. Inactive/asymptomatic carriers, patients with chronic or active HBV infection need to meet the following criteria: HBV DNA < 500 IU/mL (or 2500 copies/mL) during the screening period. Patients with HCV infection who have been cured during the screening period can be enrolled; 12. Pregnant female subjects must have a serum pregnancy test within 72 hours prior to the first dose with a negative result, and be willing to use a highly effective method of contraception during the trial and for 120 days after the last dose. For male subjects whose partner is a woman of childbearing age, they should be surgically sterile or agree to use a highly effective method of contraception for the duration of the trial and for 120 days after the last dose.

排除标准：

1.诊断为HER2阳性的胃或GEJ腺癌; 2.R1或R2切除; 3.因肿瘤出血、穿孔等并发症急诊手术； 4.既往或同时患有其他恶性肿瘤者，除非是在筛选前至少5年达到完全缓解且在研究期间不需要或预计不需要其他治疗的皮肤基底细胞癌、表浅膀胱癌、皮肤鳞状细胞癌或原位癌； 5.有以下任何一种心血管风险因素： a.研究药物首次给药前<=28天存在心源性胸痛，定义为限制日常生活器械运动的中度疼痛； b.研究药物首次给药前<=28天存在症状性肺栓塞； c.研究药物首次给药前<=6个月存在任何急性心肌梗死病史； d.研究药物首次给药前<=6个月存在任何纽约心脏协会（NYHA）分级III级或IV级的心力衰竭史； e.研究药物首次给药前<=6个月存在任何严重程度>=2级的室性心律失常事件； f.研究药物首次给药前<=6个月存在任何脑血管意外病史； g.校正后的QT间期（QTc）（用Fridericia方法校正）女性QTc≥470msec，男性QTc≥450msec，如果任何患者的初次ECG检查结果为QTc间期＞450msec（男性）或＞470msec（女性），将进行随访ECG以验证结果； h.通过多门控采集（MUGA）扫描或超声心动图（ECHO）评估，心脏左心室射血分数（LVEF）≤正常下限（LLN）。必须使用基线评估使用的同种方式进行后续评估； i.研究药物首次给药前<=28天出现的任何晕厥或癫痫发作； 6.有活动性自身免疫性疾病或者有自身免疫性疾病史但可能复发的患者； 7.在入组前7天内存在不可控制的、需要频繁引流（至少每周一次）和/或利尿剂的胸腔积液、心包积液或腹水（允许积液细胞学检查确认）； 8.在入组前1个月内出现胃肠道（GI）的临床显著出血（CTCAE>=2级）； 9.在入组前6个月内曾发生>=2级（CTCAE）胃肠穿孔和/或瘘管（包括既往胃瘘管手术）； 10.有临床意义的肠梗阻（CTCAE>=2级）； 11.已知人类免疫缺陷病毒（HIV）感染史； 12.未经治疗的慢性乙型肝炎或慢性乙型肝炎病毒（HBV）携带者（HBV DNA＞500IU/mL）或可检测到HCV RNA的活动性HCV携带者；非活动性乙型肝炎表面抗原（HBsAg）携带者、接受治疗且稳定的乙型肝炎患者（HBV DNA＜500 IU/mL）可以入组； 13.间质性肺病、非感染性肺炎或未控制的疾病史，包括肺纤维化、急性肺部疾病等； 14.研究药物首次给药前14天内，需要进行系统性抗菌、抗真菌或抗病毒治疗的严重慢性或活动性感染（包括结核菌感染等）注：允许病毒性肝炎患者接受抗病毒治疗； 15.在研究药物首次给药前<=14天，需要使用皮质类固醇（泼尼松或等效药物＞10mg/天）或其他免疫抑制药物进行系统性治疗的任何情况； 16.对替雷利珠单抗、贝伐单抗、奥沙利铂和替吉奥任何成分或对容器的任何组分存在超敏反应； 17.研究药物首次给药前<=28天需要进行全身麻醉的任何大型手术； 18.研究药物首次给药前6个月内，出血、血栓性疾病或使用抗凝剂（如华法林）或需要治疗性INR监测的类似药物； 19.既往异源性干细胞移植或器官移植； 20.在研究药物首次给药前<=28天接种过活疫苗； 21.同时参与另一项临床研究，除非为观察性（非干预性）临床研究或处于干预性研究的随访期； 22.孕妇或哺乳期女性； 23.存在研究者认为不利于研究药物给药或影响药物毒性或不良事件解读的潜在医学状况或酒精/药物滥用或依赖，或者研究者判断该患者在研究期间缺乏依从性； 24.根据研究者的判断，估计预期寿命＜3个月。

Exclusion criteria：

1. Diagnosed with HER2-positive gastric or GEJ adenocarcinoma; 2. R1 or R2 excision; 3. Emergency surgery due to tumor bleeding, perforation and other complications; 4. Those who have had other malignancies in the past or at the same time, except for basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or carcinoma in situ that has achieved complete remission at least 5 years prior to screening and does not require or is not expected to require other treatment during the study period; 5. Have any of the following cardiovascular risk factors: a. Presence of cardiogenic chest pain <=28 days prior to the first dose of study drug, defined as moderate pain that restricts the movement of instruments of daily living; b. Presence of symptomatic pulmonary embolism <=28 days prior to the first dose of study drug; c. Any history of acute myocardial infarction <=6 months prior to the first dose of study drug; d. History of any New York Heart Association (NYHA) class III or IV heart failure <=6 months prior to the first dose of study drug; e. Presence of ventricular arrhythmic events of any severity > grade 2 <=6 months prior to the first dose of study drug; f. Presence of any history of cerebrovascular accident <=6 months prior to the first dose of study drug; Corrected QT interval (QTc) (corrected with Fridericia method) QTc ≥ 470 msec for women and ≥450 msec for men, if any patient has a QTc interval of >450 msec (males) or > 470 msec (females) with a primary ECG, a follow-up ECG will be performed to verify the results; Left ventricular ejection fraction (LVEF) of the heart ≤ lower limit of normal (LLN) as assessed by multiple gated acquisition (MUGA) scan or echocardiography (ECHO). Follow-up assessments must be performed using the same modality used for baseline assessments; i. Any syncope or seizures occurring <=28 days prior to the first dose of study drug; 6. Patients with active autoimmune disease or history of autoimmune disease but may recur; 7. Presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (at least once a week) and/or diuretics within 7 days prior to enrollment (effusion cytology confirmation is allowed); 8. Clinically significant bleeding of the gastrointestinal tract (GI) within 1 month prior to enrollment (CTCAE>=grade 2); 9. Have had >=2 grade (CTCAE) gastrointestinal perforation and/or fistula (including prior gastric fistula surgery) within 6 months prior to enrollment; 10. Clinically significant intestinal obstruction (CTCAE>=grade 2); 11. Known history of human immunodeficiency virus (HIV) infection; 12. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA > 500IU/mL) or active HCV carriers with detectable HCV RNA; Patients with inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA < 500 IU/mL) may be enrolled; 13. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled disease, including pulmonary fibrosis, acute lung disease, etc.; 14. Severe chronic or active infection (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to the first dose of study drug Note: Patients with viral hepatitis are allowed to receive antiviral therapy; 15. Any condition requiring systemic treatment with corticosteroids (prednisone or equivalent> 10mg/day) or other immunosuppressive drugs prior to the first dose of study drug <=14 days; 16. Hypersensitivity to any component of tislelizumab, bevacizumab, oxaliplatin and tigio or to any component of the container; 17. Any major surgery requiring general anesthesia <=28 days prior to the first dose of study drug; 18. Bleeding, thrombotic disease, or use of anticoagulants (such as warfarin) or similar drugs requiring therapeutic INR monitoring within 6 months prior to the first dose of study drug; 19. Prior heterologous stem cell transplantation or organ transplantation; 20. Vaccination with a live vaccine prior to the first dose of study drug <=28 days; 21. Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study or is in the follow-up period of an interventional study; 22. Pregnant or lactating females; 23. Presence of an underlying medical condition or alcohol/drug abuse or dependence that, in the opinion of the investigator, is detrimental to the administration of the study drug or affects the interpretation of drug toxicity or adverse events, or the investigator judges that the patient lacks compliance during the study; 24. According to the judgment of the investigator, the estimated life expectancy < 3 months.

研究实施时间：

Study execute time：

从 From 2025-03-01 00:00:00至 To 2029-02-28 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-04-29 00:00:00 至 To 2027-02-28 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

41

Group：

Experimental group

Sample size：

干预措施：

替雷利珠单抗联合贝伐单抗及SOX方案化疗

干预措施代码：

Intervention：

Tislelizumab combined with bevacizumab and SOX chemotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China 

Province：

Shanghai 

City：

 

单位(医院)：

上海交通大学医学院附属瑞金医院 

单位级别：

三甲 

Institution
hospital：

Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

Objective Response Rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病控制率

指标类型：

次要指标

Outcome：

Disease Control Rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存期

指标类型：

次要指标

Outcome：

Progression Free Survival

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

Overall Survival

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

R0切除率

指标类型：

次要指标

Outcome：

R0 resection rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 75 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

本研究不涉及随机化，所有病例的数据将会以保密方式处理。

Randomization Procedure (please state who generates the random number sequence and by what method)：

This study does not involve randomization and data from all cases will be handled in a confidential manner.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

Blinding：

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

None

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

知情同意书等纸质材料保存在瑞金医院胃肠外科，病例数据以电子病例记录表形式保存于阿里云服务器，使用Filemaker软件构建并管理电子数据。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Paper materials such as the informed consent form are stored in the Gastrointestinal Surgery Department of Ruijin Hospital, and the clinical data are collected in the form of electronic case record forms. The electronic data is managed using Filemaker software,and stored on the Alibaba Cloud server.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2025-04-22 17:13:01