中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500100907
最近更新日期： Date of Last Refreshed on：	2025-04-17 08:13:39
注册时间： Date of Registration：	2025-04-17 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	信迪利单抗联合安罗替尼二线及后线治疗不可切除的局部晚期、复发性或转移性胃及胃食管交界处腺癌的有效性和安全性的研究
Public title：	Study on the efficacy and safety of combination therapy of Sintilimab and anlotinib in second-line and second-line treatment of unresectable locally advanced, recurrent or metastatic gastric and gastroesophageal junction adenocarcinoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	信迪利单抗联合安罗替尼二线及后线治疗不可切除的局部晚期、复发性或转移性胃及胃食管交界处腺癌的有效性和安全性的研究
Scientific title：	Study on the efficacy and safety of combination therapy of Sintilimab and anlotinib in second-line and second-line treatment of unresectable locally advanced, recurrent or metastatic gastric and gastroesophageal junction adenocarcinoma
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：	陈淼	研究负责人：	姚庆华
Applicant：	Miao Chen	Study leader：	Qinghua Yao
申请注册联系人电话： Applicant telephone：	+86 166 0571 1986	研究负责人电话： Study leader's telephone：	+86 135 8889 9111
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：	20244011@zcmu.edu.cn	研究负责人电子邮件： Study leader's E-mail：	20234052@zcmu.edu.cn
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：	浙江省杭州市潮王路318号	研究负责人通讯地址：	浙江省杭州市潮王路318号
Applicant address：	No. 318 Chaowang Road, Hangzhou, Zhejiang Province	Study leader's address：	No. 318 Chaowang Road, Hangzhou, Zhejiang Province
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：	浙江中医药大学附属第二医院
Applicant's institution：	Zhejiang University Second Affiliated Hospital of Traditional Chinese Medicine
研究负责人所在单位：	浙江中医药大学附属第二医院
Affiliation of the Leader：	Zhejiang University Second Affiliated Hospital of Traditional Chinese Medicine

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	浙中医大二院伦审2025研第038号-IH01	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：	浙江中医药大学附属第二医院医学研究伦理委员会
Name of the ethic committee：	Ethics Committee for Medical Research at the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine
伦理委员会批准日期： Date of approved by ethic committee：	2025-03-20 00:00:00
伦理委员会联系人：	黄延彪
Contact Name of the ethic committee：	Yanbiao Huang
伦理委员会联系地址：	浙江省杭州市拱墅区潮王路318号
Contact Address of the ethic committee：	No. 318 Chaowang Road, Gongshu District, Hangzhou City, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 571 8808 9970	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：

浙江中医药大学附属第二医院

Primary sponsor：

Zhejiang University Second Affiliated Hospital of Traditional Chinese Medicine

研究实施负责（组长）单位地址：

浙江省杭州市潮王路318号

Primary sponsor's address：

No. 318 Chaowang Road, Hangzhou, Zhejiang Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	浙江	市(区县)：	杭州
Country：	China	Province：	Zhejiang	City：	Hangzhou
单位(医院)：	浙江中医药大学附属第二医院	具体地址：	浙江省杭州市潮王路318号
Institution hospital：	Zhejiang University Second Affiliated Hospital of Traditional Chinese Medicine	Address：	No. 318 Chaowang Road, Hangzhou, Zhejiang Province

经费或物资来源：

企业赞助

Source(s) of funding：

Corporate sponsorship

研究疾病：

胃及胃食管交界处腺癌

Target disease：

Gastric and gastroesophageal junction adenocarcinoma

研究疾病代码：

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：

主要目的：观察信迪利单抗联合安罗替尼作为不可切除的局部晚期、复发性或转移性胃及胃食管交界处腺癌二线及后线治疗的客观缓解率（ORR）次要目的： 1. 安全性（不良事件和严重不良事件发生率） 2. 无进展生存期（PFS） 3. 总生存（OS） 4. 疾病控制率（DCR） 5. 缓解持续时间（DoR）探索性目的： 1. 评估肿瘤组织中生物标志物与疗效的关系，包括 PD-L1的表达、TMB的水平； 2. 评估外周血中生物标志物与疗效的关系，评估外周血中生物标志物与疗效的关系，包括可溶性 PD-L1 检测、CTC 检测、ctDNA 分析和细胞因子分析。

Objectives of Study：

Primary objectives: To observe the objective response rate (ORR) of sintilimab combined with anlotinib as second-line or later-line treatment for unresectable locally advanced, recurrent, or metastatic gastric and gastroesophageal junction adenocarcinoma Secondary objectives: 1. Safety (incidence of adverse events and serious adverse events) 2.Progression-free survival (PFS) 3. Overall survival (OS) 4.Disease control rate (DCR) 5.Duration of response (DoR) Exploratory objectives: 1. To evaluate the relationship between biomarkers in tumor tissue and efficacy, including PD-L1 expression and TMB levels; 2. To assess the relationship between biomarkers in peripheral blood and efficacy, including soluble PD-L1 detection, CTC detection, ctDNA analysis, and cytokine analysis.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Unresectable locally advanced, recurrent or metastatic gastric and gastroesophageal junction adenocarcinoma (including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma) confirmed by histopathological examination;
2. Body weight >=40kg; Or BMI > 18.5;
3. Age >=18 years old and <=75 years old;
4. ECOG PS score of 0-1;
5. Failure of previous standard therapy (at least 2 cycles of platinum-based and fluorouracil-based first-line therapy);
6. No systemic anti-tumor therapy within 4 weeks before the first dose of study drug;
7. At least one measurable or evaluable lesion according to RECIST, version v1.1;
8. Have adequate organ and bone marrow function, defined as follows:
(1) Blood routine: absolute neutrophil count >=1.5×10^9/L; Platelet count >=100×10^9/L; The hemoglobin level was >=9.0 g/dL.
(2) Liver function: total bilirubin (TBIL) <=1.5× upper limit of normal (ULN); TBIL<=3×ULN for patients with liver metastases or a history of Gilbert's syndrome/suspected disease (persistent or recurrent hyperbilirubinemia, mainly unconjugated hyperbilirubinemia, no evidence of hemolysis or liver lesions); For patients without HCC and liver metastasis, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5×ULN; In patients with HCC or liver metastases, ALT or AST<=5×ULN.
(3) Renal function: creatinine clearance (CCr) >=50mL/min; The results of urine dipstick test showed that urine protein was less than 2+.
(4) Coagulation function: activated partial thromboplastin time (APTT) and international normalized ratio (INR) <=1.5×ULN.
(5) Myocardial enzymes were within the normal range;
(6) Euthyroid function was defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH was beyond the normal range, the subjects could be included if the total T3 (or FT3) and FT4 were within the normal range.
9. Expected survival time >=12 weeks;
10.Female participants of childbearing age or male participants with a female partner of childbearing age were required to use an effective contraceptive method for the entire treatment period and for 6 months after the treatment period (see Section 4.3);
11. Provide written informed consent and comply with protocol-specified visits and procedures.

排除标准：

1. 已知内镜下显示病灶活动性出血征象； 2. 贲门及幽门近乎梗阻影响患者进食及胃排空，或吞食药片有障碍； 3. 既往接受VEGF或VEGFR抑制剂治疗； 4. 首次给药前 5 年内诊断为胃癌之外的其他恶性疾病（不包括经过根治的皮肤基底细胞癌、皮肤鳞状上皮癌、和/或经过根治性切除的原位癌）； 5. 有症状或高风险的梗阻、出血、穿孔、肺炎（包括既往接受过激素治疗的非传染性肺炎和正在接受治疗的肺炎患者）等； 6. 当前正在参与干预性临床研究治疗，或在首次给药前 4 周内接受过其他研究药物或使用过研究器械治疗； 7. 首次给药前 2 周内接受过具有抗肿瘤适应症的中成药或免疫调节作用的药物（包括胸腺肽、干扰素、白介素，为控制胸水或腹水局部使用的药物除外）系统性全身治疗； 8. 首次给药前2年内发生过需要全身性治疗（例如使用缓解疾病药物、糖皮质激素或免疫抑制剂）的活动性自身性免疫疾病。替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性糖皮质激素等）不视为全身性治疗； 9. 研究首次给药前7天内正在接受全身性糖皮质激素治疗（不包括喷鼻、吸入性或其他途径的局部糖皮质激素）或任何其他形式的免疫抑制疗法（>10mg/天的泼尼松或等效药物） 10. 已知异体器官移植（角膜移植除外）或异体造血干细胞移植； 11. 已知对于任何单克隆抗体或者化疗药物（卡培他滨、顺铂）制剂成分过敏（发生过 3 级及以上过敏反应）。 12. 在开始治疗前，尚未从任何干预措施引起的毒性和/或并发症中充分恢复（即，≤1 级或达到基线，不包括乏力或脱发）； 13. 已知人类免疫缺陷病毒（HIV）感染史（即 HIV 1/2 抗体阳性）； 14. 未经治疗的活动性乙肝（定义为 HBsAg 阳性同时检测到 HBV-DNA 拷贝数大于所在研究中心检验科正常值上限）；注：符合下列标准的乙肝受试者亦可入组： a) 首次给药前HBV病毒载量<1000拷贝/ml（200IU/ml），受试者应在整个研究化疗药物治疗期间接受抗HBV治疗避免病毒再激活 b) 对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活 15. 活动性的 HCV 感染受试者（HCV 抗体阳性且 HCV-RNA 水平高于检测下限）； 16. 首次给药之前（第 1 周期，第 1 天）30 天内接种过活疫苗；注：允许首次给药前 30 天内接受针对季节性流感的注射用灭活病毒疫苗；但是不允许接受鼻内用药的减毒活流感疫苗。 17. 妊娠或哺乳期妇女； 18. 存在任何严重或不能控制的全身性疾病，例如： a) 静息心电图在节律、传导或形态上出现有重大且症状严重难以控制的异常，如完全性左束支传导阻滞，Ⅱ度以上心脏传导阻滞，室性心律失常或心房颤动； b) 不稳定型心绞痛，充血性心力衰竭，纽约心脏病协会（NYHA）分级≥ 2 级的慢性心衰； c) 在入选治疗前 6 个月内发生过任何动脉血栓、栓塞或缺血，如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作等； d) 血压控制不理想（收缩压＞140 mmHg，舒张压＞90 mmHg）； e) 首次给药前 1 年内存在需要糖皮质激素治疗的非感染性肺炎病史，或当前存在临床活动性间质性肺病； f) 活动性肺结核； g) 存在需要全身性治疗的活动性或未能控制的感染； h) 存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻； i) 肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎； j) 糖尿病控制不佳（空腹血糖（FBG）＞10mmol/L）； k) 尿常规提示尿蛋白≥++，且证实 24 小时尿蛋白定量＞1.0 g 者； l) 存在精神障碍且无法配合治疗的患者； 19. 有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况研究者认为存在其他潜在风险不适合参加本研究。

Exclusion criteria：

1. Known signs of active bleeding under endoscopy; 2. Obstruction of the cardia and pylorus may affect the patient's eating and gastric emptying, or may cause difficulty in swallowing tablets; 3. Prior treatment with a VEGF or VEGFR inhibitor; 4. Malignant diseases other than gastric cancer diagnosed within 5 years before the first dose (excluding radical skin basal cell carcinoma, skin squamous cell carcinoma, and/or radical resection in situ carcinoma); 5. Symptomatic or high-risk obstruction, bleeding, perforation, pneumonia (including patients with non-communicable pneumonia who had received hormone therapy in the past and patients with pneumonia who were receiving treatment); 6. Are currently participating in an interventional clinical study treatment, or have received another study drug or study device within 4 weeks before the first dose; 7. Received anti-tumor indications of Chinese patent medicine or immunomodulatory drugs (including thymosin, interferon, interleukin, except drugs used locally to control pleural effusion or ascites) systemic treatment within 2 weeks before the first dose; 8. Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) were not considered systemic therapy; 9. Receiving systemic glucocorticoids (excluding topical glucocorticoids by nasal spray, inhalation, or other route) or any other form of immunosuppressive therapy (>10mg/ day of prednisone or equivalent) within 7 days before the first study dose 10. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 11. Known allergy to any monoclonal antibody or chemotherapy drug (capecitabine, cisplatin) ingredients (grade 3 or above anaphylaxis). 12. Has not fully recovered from any intervention-related toxicity and/or complications before starting treatment (i.e., grade <=1 or baseline, excluding fatigue or alopecia); 13. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive); 14. Untreated active hepatitis B (defined as both HBsAg positivity and HBV-DNA copies greater than the upper limit of normal in the laboratory of the participating center); Note: Subjects with hepatitis B who met the following criteria were also eligible for inclusion: a) HBV viral load <1000 copies /ml (200IU/ml) before the first dose, subjects should receive anti-HBV therapy throughout the study chemotherapy drug treatment to avoid viral reactivation b) Subjects with anti-HBc (+), HBsAg (-), anti-hbs (-), and HBV viral load (-) do not require prophylactic anti-HBV therapy, but close monitoring for viral reactivation is required 15. Active HCV-infected subjects (HCV-antibody positive and HCV-RNA level above the lower limit of detection); 16. Received a live vaccine within 30 days before the first dose (cycle 1, day 1); Note: Administration of injectable inactivated virus vaccine against seasonal influenza within 30 days before the first dose is allowed; Live, attenuated, intranasal influenza vaccine was not allowed. 17. Pregnant or lactating women; 18. The presence of any serious or uncontrolled systemic illness, such as: a) significant rhythm, conduction or morphological abnormalities on resting ECG that are symptomatic and difficult to control, such as complete left bundle branch block, >= Ⅱ degree heart block, ventricular arrhythmia or atrial fibrillation; b) unstable angina, congestive heart failure, New York Heart Association (NYHA) class >= 2 chronic heart failure; c) any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, etc. within 6 months before enrollment; d) suboptimal blood pressure control (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); e) a history of noninfectious pneumonia requiring glucocorticoid therapy within 1 year before the first dose or current clinically active interstitial lung disease; f) active pulmonary tuberculosis; g) presence of active or uncontrolled infection requiring systemic therapy; h) clinically active diverticulitis, abdominal abscess, and gastrointestinal obstruction; i) liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; j) poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L); k) urine routine showed urinary protein >=++ and confirmed 24-hour urinary protein quantitation > 1.0 g; l) patients with mental disorders who are unable to cooperate with treatment; 19. Medical history or evidence of disease, treatment or laboratory abnormalities, or other conditions deemed by the investigator to be inappropriate for enrollment that might interfere with the results of the trial or prevent the participant from participating fully in the study.

研究实施时间：

Study execute time：

从 From 2025-03-21 00:00:00至 To 2027-03-21 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-04-30 00:00:00 至 To 2026-04-30 00:00:00

干预措施：

Interventions：

组别：	治疗组	样本量：	32
Group：	Treatment group	Sample size：	32
干预措施：	信迪利单抗：200mg IV d1 Q3W 安罗替尼：12mg QD 2周/停1周 Q3W	干预措施代码：
Intervention：	Sintilimab: 200 mg IV on day 1 every 3 weeks Anlotinib: 12 mg daily for 2 weeks, then 1 week off, repeated every 3 weeks	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江	市(区县)：	杭州
Country：	China	Province：	Zhejiang	City：	Hangzhou
单位(医院)：	浙江中医药大学附属第二医院	单位级别：	三甲
Institution hospital：	Zhejiang University Second Affiliated Hospital of Traditional Chinese 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, ORR	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, 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：	缓解持续时间	指标类型：	次要指标
Outcome：	Duration of remission, DoR	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, PFS	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	安全性	指标类型：	次要指标
Outcome：	Safety	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	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：

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）：

无

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

None

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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	否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)：	N/A
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：	病例记录表。无电子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Case Record Form, CRF.No Electronic Data Capture, EDC
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 08:13:34