ChiCTR2500100982 版本V1.0 版本创建时间2025/04/17 16:22:06 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：

ChiCTR2500100982 

最近更新日期：

Date of Last Refreshed on：

2025-04-17 16:21:59 

注册时间：

Date of Registration：

2025-04-17 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

PD-1抗体卡瑞利珠单抗联合阿帕替尼用于不可切除的III、IV期dMMR胃癌转化治疗的单中心、II期临床研究

Public title：

PD-1 antibody carilizumab combined with apatinib for unresectable stage III and IV dMMR gastric cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

PD-1抗体卡瑞利珠单抗联合阿帕替尼用于不可切除的III、IV期dMMR胃癌转化治疗的单中心、II期临床研究

Scientific title：

PD-1 antibody carilizumab combined with apatinib for unresectable stage III and IV dMMR gastric cancer

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：

姚艳红 

研究负责人：

曹宝山 

Applicant：

Yanhong Yao 

Study leader：

Baoshan Cao 

申请注册联系人电话：

Applicant telephone：

+86 10 8226 5857

研究负责人电话：

Study leader's telephone：

+86 10 8226 4635

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：

snowdream246@163.com

研究负责人电子邮件：

Study leader's E-mail：

snowdream246@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

PekingUTH

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：

北京市海淀区花园北路49号

研究负责人通讯地址：

北京市海淀区花园北路49号

Applicant address：

49 North Garden Road, Haidian, Beijing, China

Study leader's address：

49 North Garden Road, Haidian, Beijing, China

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：

北京大学第三医院

Applicant's institution：

Peking University Third Hospital

研究负责人所在单位：

北京大学第三医院

Affiliation of the Leader：

Peking University Third Hospital

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：

(2022)医伦审第(294-02)号; (2022)医伦审第(294-03)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：

北京大学第三医院医学科学伦理委员会

Name of the ethic committee：

Peking University Third Hospital Medical Science Research Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2022-07-20 00:00:00

伦理委员会联系人：

宋纯理

Contact Name of the ethic committee：

Chunli Song

伦理委员会联系地址：

北京市海淀区花园北路49号

Contact Address of the ethic committee：

49 North Garden Road, Haidian, Beijing, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 10 8226 5573

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：

北京大学第三医院

Primary sponsor：

Peking University Third Hospital

研究实施负责（组长）单位地址：

北京市海淀区花园北路49号

Primary sponsor's address：

49 North Garden Road, Haidian, Beijing, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

北京大学第三医院

具体地址：

北京市海淀区花园北路49号

Institution
hospital：

Peking University Third Hospital

Address：

49 North Garden Road, Haidian, Beijing, China

经费或物资来源：

自筹

Source(s) of funding：

self-collected

Target disease：

Gastric cancer

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评估PD-1抗体卡瑞利珠单抗联合阿帕替尼用于不可切除III、Ⅳ期dMMR胃癌转化治疗的安全性和有效性。  

Objectives of Study：

To evaluate the safety and efficacy of the PD-1 antibody camrelizumab in combination with apatinib for the conversion therapy of unresectable stage III and IV dMMR gastric cancer.

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.年龄大于等于18岁，性别不限； 2.经组织学确诊的不可切除的III、Ⅳ期dMMR（MLH1, PMS2, MSH2及MSH6至少一种蛋白完全缺失，如MLH1缺失，需检测甲基化进一步确认）胃腺癌（Gastric cancer, GC）（神经内分泌瘤除外）或胃食管结合部腺癌（Gastricesophageal Junction adenocarcinoma, GEJ）； 3.有转化治疗潜能的不可切除胃癌患者，定义为单一器官转移（如肝转移、卵巢转移、肺转移）、腹膜后淋巴结转移、锁骨上淋巴结转移、局限腹膜转移、侵犯周围脏器以及其他研究者评估可行转化治疗的胃癌患者； 4.先前未经过手术、放疗、免疫治疗； 5.ECOG PS评分0-1分； 6.预计生存期>=3个月； 7.主要脏器功能正常，无严重血液、心、肺、肝、肾、骨髓等功能异常和免疫缺陷疾病； 8.凝血功能正常，无活动性出血和血栓形成疾病； 9.既往使用过抗肿瘤的中药、中成药、免疫调节剂（如胸腺肽、白介素等）结束距开始研究用药必须>=2周； 10.非手术绝育或育龄期女性受试者，需要在研究治疗期间和研究治疗结束后 180 天内采用一种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套）；非手术绝育的育龄期女性受试者在随机前的 72 h 内血清 HCG 检查必须为阴性；而且必须为非哺乳期；对于伴侣为育龄妇女的男性受试者，应在研究治疗期间和研究治疗期结束后 180 天内采用有效方法避孕。 11. 受试者自愿参加本研究，完全了解、知情本研究并且签署知情同意书（Informed Consent Form, ICF）； 12.预计依从性好者，能按方案要求随访疗效及不良反应； 13.有足够样本用于探索性研究。

Inclusion criteria

1. Age greater than or equal to 18 years old, gender not limited; 2. Histologically confirmed unresectable stage III and IV dMMR (complete loss of at least one protein, MLH1, PMS2, MSH2, and MSH6), gastric adenocarcinoma (GC) (excluding neuroendocrine tumors) or gastroesophageal junction adenocarcinoma (GEJ); 3.Unresectable gastric cancer patients with potential for conversion therapy, defined as gastric cancer patients with single organ metastasis (such as liver metastasis, ovarian metastasis, lung metastasis), retroperitoneal lymph node metastasis, supraclavicular lymph node metastasis, localized peritoneal metastasis, invasion of surrounding organs, and other gastric cancer patients evaluated by researchers as feasible for conversion therapy; 4. Without surgery, radiation therapy, or immunotherapy for the gastric cancer lesion or metastatic tumor. 5. ECOG PS score 0-1 points; 6. Expected survival period >= 3 months; 7. The main organ functions are normal, and there are no severe abnormalities in blood, heart, lung, liver, kidney, bone marrow, or immunodeficiency diseases. 8. Normal coagulation function, no active bleeding or thrombotic diseases: 9. The time from the end of traditional Chinese medicine, traditional Chinese patent medicines and simple preparations and immunomodulator (such as thymosin, interleukin, etc.) that have used anti-tumor drugs in the past to the start of the study must be >= 2 weeks; 10. Non surgical sterilization or female subjects of childbearing age are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 180 days after the end of the study treatment; Female subjects of childbearing age who undergo non-surgical sterilization must have a negative serum HCG test within 72 hours prior to randomization; And it must be during non lactation period; For male participants whose partners are women of childbearing age, effective contraception methods should be used during the study treatment period and within 180 days after the end of the study treatment period. 11 Subjects voluntarily participated in this study, fully understood and informed of the study, and signed the Informed Consent Form (ICF); 12. Those who are expected to have good compliance can follow up the efficacy and adverse reactions according to the requirements of the protocol; 13. Have sufficient samples for exploratory studies.

排除标准：

1.首次使用研究药物前5年内已诊断为其他恶性肿瘤，经有效治疗的皮肤基底细胞癌、皮肤鳞状细胞癌和/或经有效切除的原位宫颈癌和/或乳腺癌和/或甲状腺癌等获得长期生存的恶性肿瘤除外； 2.已经或正在接受额外化疗、放射治疗、靶向或免疫治疗的受试者； 3.患有任何活动性自身免疫疾病或自身免疫疾病史，如间质性肺炎、葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、心肌炎、肾炎、甲状腺功能亢进、甲状腺功能降低（治疗后激素水平稳定的患者除外）；患有童年期哮喘已完全缓解且成人后无需任何干预或白癜风可纳入，需要支气管扩张剂进行医学干预的受试者则不可纳入； 4.患有先天或后天免疫功能缺陷，如人类免疫缺陷病毒（HIV）感染者，活动性乙型肝炎（HBV DNA >= 500 IU/ml），丙型肝炎（丙肝抗体阳性，且HCV-RNA高于分析方法的检测下限）或合并乙肝和丙肝共同感染； 5.首次使用研究药物前14天之内使用过免疫抑制药物，不包括喷鼻和吸入性皮质类固醇或生理剂量的系统性类固醇激素（即不超过10 mg/天强的松龙或同等药物生理学剂量的其他皮质类固醇）； 6.首次给药前4周内或计划在研究期间接种减毒活疫苗； 7.患有高血压病，经降压药物治疗无法降至正常范围者（收缩压<=140 mmHg / 舒张压<= 90 mmHg）； 8.3 个月内出现过显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、有出血危险的食管胃底静脉曲张、出血性胃溃疡或患有脉管炎等；筛选期需要进行胃镜检查，若胃镜结果提示有重度胃溃疡或研究者判断有出血风险则不能入组（3 个月及以内接受胃镜检查排除此类情况且筛选期便潜血阴性者除外）；6 个月内出现过胃肠道穿孔或胃肠道瘘； 9.患有未能控制的心脏临床症状或疾病，如（1）NYHA II级及以上心力衰竭，（2）不稳定型心绞痛，（3）1年内发生过心肌梗死，（4）控制不良的心律失常； 10.既往和目前存在间质性肺炎、尘肺、放射性肺炎、药物相关肺炎等，肺功能严重受损等可能会干扰可疑的药物相关肺毒性的检测和处理的患者； 11.患有活动性肺结核； 12.首次用药前4周内并发重度感染（如：需要静脉滴注抗生素、抗真菌或抗病毒药物），或在筛选期间/首次给药前出现不明原因的发热（体温>= 38.5°C）； 13.已知异体器官移植史或异体造血干细胞移植史； 14.存在脑转移受试者； 15.已知对本方案药物组分有过敏史者； 16.存在可能增加参与研究和研究用药风险，或其他重度、急性和慢性疾病； 17.研究者认为不适合纳入的其他情况。

Exclusion criteria：

1. Other malignant tumors have been diagnosed within 5 years prior to the first use of the study drug, except for malignancies with long-term survival such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or in situ cervical cancer and/or breast cancer and/or thyroid cancer that have been effectively treated; 2. Subjects who have received or are receiving additional chemotherapy, radiotherapy, targeted or immunotherapy; 3. Have any active autoimmune disease or history of autoimmune disease, such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (except for patients with stable hormone levels after treatment); Subjects with childhood asthma who have been in complete remission and do not require any intervention in adulthood or vitiligo may be included, but participants requiring medical intervention with bronchodilators cannot be included; 4. Patients with congenital or acquired immunodeficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV DNA >= 500 IU/ml), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the lower limit of detection of the analytical method) or co-infection with hepatitis B and hepatitis C; 5. Use of immunosuppressive medications, excluding nasal spray and inhaled corticosteroids or physiologic doses of systemic steroids (i.e., no more than 10 mg/day prednisolone or other corticosteroids at equivalent pharmacophysiological doses) within 14 days prior to the first dose of study drug; 6. Vaccination with live attenuated vaccine within 4 weeks prior to the first dose or planned administration during the study; 7. Patients with hypertension who cannot be reduced to the normal range after antihypertensive drug treatment (systolic blood pressure <= 140 mmHg / diastolic blood pressure <= 90 mmHg); 8. Have had significant clinically significant bleeding symptoms or have a definite bleeding tendency within 3 months, such as gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, hemorrhagic gastric ulcer or vasculitis, etc.; Gastroscopy is required during the screening period, and if the results of the gastroscopy indicate severe gastric ulcer or the investigator judges that there is a risk of bleeding, it cannot be enrolled (except for those who undergo gastroscopy within 3 months to rule out such conditions and have negative occult blood during the screening period); Gastrointestinal perforation or gastrointestinal fistula within 6 months; 9. Have uncontrolled cardiac clinical symptoms or diseases, such as (1) NYHA class II and above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, (4) poorly controlled arrhythmia; 10. Patients with previous and current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, etc., with severe impairment of lung function that may interfere with the detection and management of suspected drug-related pulmonary toxicity; 11. Have active tuberculosis; 12. Concurrent severe infection (e.g., need for intravenous antibiotics, antifungal or antiviral drugs) within 4 weeks prior to the first dose, or unexplained fever (temperature >= 38.5°C) during screening/before the first dose; 13. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 14. Subjects with brain metastases; 15. Those who are known to have a history of allergy to the drug components of this protocol; 16. Presence of conditions that may increase the risk of participation in the study and study medications, or other severe, acute, and chronic diseases; 17. Other situations that the investigator considers inappropriate for inclusion.

研究实施时间：

Study execute time：

从 From 2023-04-25 00:00:00至 To 2026-04-24 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-11-26 00:00:00 至 To 2026-04-19 00:00:00  

干预措施：

Interventions：

组别：

治疗组

样本量：

20

Group：

Therapy group

Sample size：

干预措施：

卡瑞利珠单抗和阿帕替尼

干预措施代码：

Intervention：

camrelizumab and apatinib

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

北京大学第三医院 

单位级别：

三甲 

Institution
hospital：

Peking University Third Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

1年无疾病进展生存率

指标类型：

主要指标

Outcome：

The rate of 1 year Progression Free Survival (PFS)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

可手术患者主要病理缓解率

指标类型：

次要指标

Outcome：

Main Pathological Response Rate (MPR)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

可手术患者R0切除率

指标类型：

次要指标

Outcome：

Margin-free (R0) resection 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：

总生存期

指标类型：

次要指标

Outcome：

Overall survival (OS)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观缓解率

指标类型：

次要指标

Outcome：

Objective response rate (ORR)

Type：

Secondary 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 (DCR)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件（AE）及严重不良事件（SAE）

指标类型：

次要指标

Outcome：

Averse event (AE) and serious averse event (SAE)

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：

正在进行

Recruiting

年龄范围：

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

非随机方法

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

Non-Randomization Procedure

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

Yes

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）：

试验结束后于2026-10-20后在临床试验公共管理平台（ResMan）公开数据，网址：http://www.medresman.org.cn/login.aspx

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

After the end of the trial, the data will be publicly available on the clinical trial public management platform (ResMan) after October 20, 2026, at the following website: http://www.medresman.org.cn/login.aspx

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：

病例报告表由研究者填写，每个入选病例必须完成病例报告表。完成的病例报告表进行数据录入与管理工作。所有原始数据均由开展研究科室保留。

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

The case report form is completed by the investigator and each selected case must complete a case report form. Completed case report forms for data entry and management. All raw data are retained by the department conducting the study.

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：

  2025-04-17 16:21:59