ChiCTR2300069825 版本V1.1 版本创建时间2023/06/02 12:47:17 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：

ChiCTR2300069825 

最近更新日期：

Date of Last Refreshed on：

2023-03-27 12:35:57 

注册时间：

Date of Registration：

2023-03-27 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

探索淋巴细胞亚群及细胞因子在胃癌免疫治疗过程中的动态变化与疗效及不良反应的关系

Public title：

To explore the dynamic changing regularity of lymphocyte subgroups and cytokines in immunotherapy for gastric cancer and its relationship with efficacy and adverse reaction

注册题目简写：

English Acronym：

研究课题的正式科学名称：

探索淋巴细胞亚群及细胞因子在胃癌免疫治疗过程中的动态变化与疗效及不良反应的关系

Scientific title：

To explore the dynamic changing regularity of lymphocyte subgroups and cytokines in immunotherapy for gastric cancer and its relationship with efficacy and adverse reaction

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：

杨苗苗 

研究负责人：

刘爱娜 

Applicant：

Yang Miaomiao 

Study leader：

Liu aina 

申请注册联系人电话：

Applicant telephone：

18660055228

研究负责人电话：

Study leader's telephone：

13906388003

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：

sdcandy1224@126.com

研究负责人电子邮件：

Study leader's E-mail：

nana4312@sina.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：

山东省烟台市芝罘区毓璜顶东路20号

研究负责人通讯地址：

山东省烟台市芝罘区毓璜顶东路20号

Applicant address：

20 Yuhuangding East Road, Yantai, Shandong, P.R. China.

Study leader's address：

20 Yuhuangding East Road, Yantai, Shandong, P.R. 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：

烟台毓璜顶医院

Applicant's institution：

Yantai Yuhuangding Hospital

研究负责人所在单位：

烟台毓璜顶医院

Affiliation of the Leader：

Yantai Yuhuangding 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：

烟毓医伦理审【2022-40】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：

烟台毓璜顶医院伦理委员会

Name of the ethic committee：

ethics committee of Yantai Yuhuangding Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2022-04-13 00:00:00

伦理委员会联系人：

高振利

Contact Name of the ethic committee：

Gao Zhenli

伦理委员会联系地址：

山东省烟台市芝罘区毓璜顶东路20号

Contact Address of the ethic committee：

20 Yuhuangding East Road, Yantai, Shandong, P.R. China.

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

烟台毓璜顶医院

Primary sponsor：

Yantai Yuhuangding Hospital

研究实施负责（组长）单位地址：

山东省烟台市芝罘区毓璜顶东路20号

Primary sponsor's address：

20 Yuhuangding East Road, Yantai, Shandong, P.R. 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)：

山东省

市(区县)：

烟台

Country：

China

Province：

Shandong

City：

Yantai

单位(医院)：

毓璜顶医院

具体地址：

山东省烟台市芝罘区毓璜顶东路20号

Institution
hospital：

Yuhuangding Hospital

Address：

20 Yuhuangding East Road, Yantai, Shandong, P.R. China.

经费或物资来源：

申请经费+自筹经费

Source(s) of funding：

resources requested and self-financing

Target disease：

gastric cancer

Target disease code：

研究类型：

病因学/相关因素研究

Study type：

Cause/Relative factors study

研究所处阶段：

 诊断试验新技术临床试验 

Study phase：

Diagnostic New Technique Clincal Study

研究设计：

病例研究 

Study design：

Case study 

研究目的：

通过分析胃癌患者免疫治疗前、中、后外周血淋巴细胞亚群和细胞因子的动态变化，探讨该变化与免疫治疗疗效及不良反应的关系，为胃癌患者的免疫状态提供有效的数据，也可为胃癌患者的免疫治疗提供进一步的科学依据。该研究目前国内外均未见报道，因此本研究结果对于胃癌患者的精准免疫治疗具有重要的临床意义。  

Objectives of Study：

Based on analyzing the dynamic change of peripheral blood lymphocyte subsets and cytokines before, during and after the immunotherapy of patients with gastric cancer, Our objective was to explore the relationship between the change and the immunotherapy efficacy and adverse reaction. The result may provide effective data for the immune status in patients with gastric cancer and provide the scientific basis for patients with gastric cancer immunotherapy. This study has not been reported at home and abroad, so the results of this study have important clinical significance for precision immunotherapy of gastric cancer patients.

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.患者自愿加入本研究，并签署知情同意书；
2.男性或女性，年龄≥18岁；
3.ECOG PS评分 0-2；
4.病理学确诊的胃/胃食管胃结合部腺癌；
5.具有胃外可测量病灶（RECIST 1.1标准）；
6.受试者基线血常规和生化指标符合下列标准（首次用药前14 天内未输血或血液制品，未使用G-CSF及其他造血刺激因子纠正）：
血红蛋白≥90g/L；
中性粒细胞绝对计数（ANC）≥1.5×109/L；
血小板≥80×109/L；
ALT、AST ≤ 2.5 倍正常上限值；如患者伴有肝转移则ALT和AST ≤ 5倍正常值上限；
血清总胆红素≤1.5倍正常上限值；
血清 Cr≤1.5倍正常值上限或内生肌酐清除率>50ml/min（男性：内生肌酐清除率 =((140-年龄 ) ×体重 )/(72×血清 Cr)；女性：内生肌酐清除率 =((140-年龄 ) ×体重 )/ (72×血清 Cr) × 0.85；体重单位：kg；血清 Cr单位 : mg/mL）；
血清白蛋白≥30g/L；
7.无严重的使生存期< 5年的伴随疾病；
8.患者依从性良好，能够遵守研究期间的方案；
9.有妊娠能力的女性受试者需要在首次用药前72h内进行血清妊娠试验且结果为阴性，并同意研究治疗期间和治疗结束后90天内采取高效方法避孕；对于伴侣为有生育能力女性的男性受试者，应同意在治疗期间和治疗结束后90天内采用高效方法避孕；
10.同意提供血液和/或组织学标本。

Inclusion criteria

1. Patients volunteered to participate in this study and signed informed consent;
2. Male or female, aged ≥18 years;
3.ECOG PS score 0-2;
4. Gastric/gastroesophageal junction adenocarcinoma confirmed by pathology;
5. External measurable lesions (RECIST 1.1);
6. The baseline blood routine and biochemical parameters of the subjects met the following criteria (no blood transfusion or blood products, no G-CSF or other hematopoietic stimulating factors were used within 14 days before the first medication) :
Hemoglobin ≥90g/L;
Absolute neutrophil count (ANC) ≥1.5×109/L;
Platelets ≥80×109/L;
ALT and AST ≤ 2.5 times the upper limit of normal; ALT and AST ≤ 5 times the upper limit of normal if patients with liver metastases;
Serum total bilirubin ≤1.5 times the upper limit of normal;
Serum Cr≤1.5 times the upper limit of normal value or endogenous creatinine clearance >50ml/min (male: endogenous creatinine clearance =((140- age) × body weight)/(72× serum Cr); Female: Endogenous creatinine clearance =((140- age) × weight)/ (72× serum Cr) × 0.85; Weight unit: kg; Serum Cr unit: mg/mL);
Serum albumin ≥30g/L;
7. No serious concomitant diseases that make the survival time less than 5 years;
8. Patients had good compliance and could comply with the protocol during the study;
9. Female subjects who are capable of pregnancy are required to have a negative serum pregnancy test within 72 hours before the first dose and to agree to use highly effective methods of contraception during the study treatment and for 90 days after the end of treatment; Male subjects with a fertile female partner should agree to use highly effective methods of contraception during treatment and for 90 days after the end of treatment;
10. Consent to provide blood and/or histological specimens.

排除标准：

1.妊娠或哺乳期妇女；
2.先前治疗引起的不良事件（脱发除外）未恢复至≤1级的患者（CTCAE v5.0）；
3.最近5年内或同时患有其他恶性疾病史者，治愈的皮肤基底细胞癌和宫颈原位癌除外；
4.有未控制的癫痫、中枢神经系统疾病或精神障碍史者，由研究者判断其临床严重性是否妨碍签署知情同意书或影响患者口服药物的依从性；
5.未能良好控制的临床上严重的（即活动的）心脏病，如：(1) 有症状的冠心病，(2) 纽约心脏病协会（NYHA）II级或更严重的充血性心力衰竭或严重的需药物干预的心律失常，(3) 最近12个月内发生过心肌梗死，(4) QTc间期男性≥450ms，女性≥470ms，(5) LVEF<50%；
6.6 个月内发生的动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作、脑出血、脑梗塞）、深静脉血栓及肺栓塞等；
7.3个月内出现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、出血性胃溃疡等，筛选期若大便潜血阳性，可复查，复查若仍为阳性，结合临床判断必要时进行胃镜检查（入组前3个月内接受过胃镜检查排除此类情况者除外）。
8.已知存在的遗传性或获得性出血及血栓倾向（如血友病人，凝血机能障碍，血小板减少等）；
9.既往发生过胃肠道穿孔、腹腔脓肿或近3个月内发生过肠梗阻或影像学、临床症状提示伴有肠梗阻的患者；
10.凝血功能异常（INR>2.0或凝血酶原时间>16s），具有出血倾向或正在接受溶栓或抗凝治疗（允许预防性使用小剂量阿司匹林、低分子肝素等）；
11.器官移植需要免疫抑制治疗者；用药前14天内使用免疫抑制药物或全身皮质类固醇治疗以达到免疫抑制目的的患者（如＞10mg/天泼尼松或其他药物等效剂量）；
12.伴有活动性溃疡、未愈合创口或伴有骨折；
13.患有高血压，且经降压药物治疗无法获得良好控制者（收缩压≥140 mmHg或者舒张压≥90 mmHg）；
14.既往接受过PD1/PD-L1单抗免疫治疗；
15.尿常规提示尿蛋白≥ ++并经证实24小时尿蛋白量>1.0 g；
16.有临床症状需要对症处理的浆膜腔积液（包括腹水、胸水、心包积液）；无症状的浆膜腔积液患者允许入组；有症状的浆膜腔积液经引流等积极处理得到良好控制的患者，经研究者判断允许入组；
17.活动性肝炎（乙肝参考：HBsAg阳性且HBV DNA≥500 IU/ml；丙肝参考：HCV抗体阳性且HCV病毒拷贝数>正常值上限）；处于活动性感染阶段需要抗微生物治疗的患者（如抗细菌药物治疗、抗真菌药物治疗）；
18.目前伴有间质性肺炎或间质性肺病，或其他可能干扰免疫相关肺毒性判断和处理的肺纤维化、机化性肺炎、尘肺、药物相关性肺炎、特发性肺炎、或筛选期CT显示患有活动性肺炎或严重肺功能损害者；活动性肺结核者；
19.具有活动性自身免疫性疾病或有自身免疫病病史且可能复发的患者（包括但不限于免疫性肝炎、间质性肺炎、葡萄膜炎、肠炎、垂体炎、血管炎、肾炎、甲状腺功能亢进、甲状腺功能降低[通过激素替代治疗可以控制的受试者可纳入]）；不需要全身治疗的皮肤疾病（如白斑病、银屑病、脱发），经胰岛素治疗可控制的I型糖尿病患者或曾患有儿童时期哮喘已完全缓解无需任何干预措施的患者可以入组；需要支气管扩张剂进行干预的哮喘患者不能入组；
20.经研究者判断，受试者有其他可能影响试验结果或导致本研究被迫中途停止的因素，如酗酒、药物滥用、其他的严重疾病（含精神疾病）需要合并治疗，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到患者的安全。

Exclusion criteria：

1. Pregnant or lactating women;
2. Patients whose adverse events (other than hair loss) caused by previous treatment did not recover to grade ≤1 (CTCAE V5.0);
3. Patients with a history of other malignant diseases within the last 5 years or at the same time, except cured basal cell carcinoma of the skin and cervical carcinoma in situ;
4. If there is a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the clinical severity of the disease will be judged by the researcher whether it prevents the signing of informed consent or affects the patient's oral medication compliance;
5. Clinically serious (i.e. active) heart disease that is not well controlled, such as: (1) symptomatic coronary heart disease, (2) New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring medical intervention, (3) previous myocardial infarction within the last 12 months, (4) QTc interval ≥450ms for men and ≥470ms for women, (5) LVEF<50%;
6.Arteriovenous thrombotic events occurring within the last 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
7.3 months significant clinical significance of bleeding symptoms or has a definite bleeding tendency, such as gastrointestinal bleeding, bleeding ulcers, screening period if defecate occult blood positive, to review, review if still positive, combined with clinical judgment when necessary for gastroscopy (group in the first 3 months received gastroscopy except of ruled out such a situation).
8. Known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophilia, coagulopathy, thrombocytopenia, etc.);
9. Patients with previous gastrointestinal perforation, abdominal abscess, or intestinal obstruction in the past 3 months or with imaging and clinical symptoms suggestive of intestinal obstruction;
10. Abnormal coagulation function (INR>2.0 or prothrombin time >16s), bleeding tendency or undergoing thrombolytic or anticoagulant therapy (allowing prophylactic use of low-dose aspirin, low molecular weight heparin, etc.);
11. Those who need immunosuppressive therapy for organ transplantation; Patients who have been treated with immunosuppressive agents or systemic corticosteroids to achieve immunosuppression within 14 days prior to treatment (e.g., prednisone > 10mg/ day or equivalent);
12. With active ulcer, unhealed wound or fracture;
13. Patients with hypertension that cannot be well controlled with antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
14. Previously received PD1/PD-L1 mab immunotherapy;
15. Urine routine indicated urinary protein ≥ ++ and confirmed 24-hour urinary protein > 1.0g;
16. Serous effusion (including ascites, pleural effusion and pericardial effusion) with clinical symptoms requiring symptomatic treatment; Asymptomatic patients with serosal effusion were allowed to be enrolled. Patients with symptomatic serosal effusion that had been well controlled by active treatment such as drainage were allowed to be enrolled in the study.
17. Active hepatitis (hepatitis B reference: HBsAg positive with HBV DNA≥500 IU/ml; HCV reference: HCV antibody positive and HCV virus copy number > the upper limit of normal); Patients in the active stage of infection who require antimicrobial therapy (e.g., antimicrobial therapy, antifungal therapy);
18. Patients with current interstitial pneumonia or interstitial lung disease, or other pulmonary fibrosis, organizing pneumonia, pneumoconiosis, drug-associated pneumonia, idiopathic pneumonia, or active pneumonia or severe pulmonary function impairment as shown by CT during the screening period that may interfere with the judgment and management of immune-related pulmonary toxicity; Active pulmonary tuberculosis;
19. With active autoimmune disease or a history of autoimmune disease and may relapse patients (including but not limited to, autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, the pituitary gland inflammation, vasculitis, nephritis, thyroid function, thyroid function decrease [by hormone replacement therapy can control the subjects can be incorporated into]); Patients with skin conditions that do not require systemic treatment (e.g., leukoplakia, psoriasis, alopecia) who have type I diabetes that can be controlled with insulin therapy or who have had a complete remission of childhood asthma without any intervention may be enrolled; Patients with asthma who required intervention with bronchodilators were excluded;
20. Judging by the researchers, there are other participants may affect the test result or cause of this study was forced to stop halfway to factors, such as alcoholism, drug abuse, and other serious disease (including mental illness) need to merge treatment, there are serious abnormal laboratory examination, accompanied by factors such as family or society, can affect the safety of the patients.

研究实施时间：

Study execute time：

从 From 2022-06-01 00:00:00至 To 2024-05-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-03-29 00:00:00 至 To 2023-12-31 00:00:00  

干预措施：

Interventions：

组别：

患者组

样本量：

50

Group：

patient group

Sample size：

干预措施：

免疫治疗

干预措施代码：

Intervention：

immunotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 山东省 

市(区县)：

 烟台 

Country：

China 

Province：

Shandong 

City：

Yantai 

单位(医院)：

毓璜顶医院 

单位级别：

三级甲等 

Institution
hospital：

Yuhuangding Hospital

Level of the institution：

tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

Progress Free Survival

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：

主要指标

Outcome：

Disease control 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：

不良事件

指标类型：

主要指标

Outcome：

adverse events

Type：

Primary indicator

测量时间点：

治疗过程中

测量方法：

Measure time point of outcome：

During treatment procedure

Measure method：

指标中文名：

淋巴细胞亚群和细胞因子水平

指标类型：

主要指标

Outcome：

Lymphocyte subpopulations and cytokine levels

Type：

Primary indicator

测量时间点：

治疗前、治疗中、治疗进展后

测量方法：

Measure time point of outcome：

Before, during, and after treatment progress

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 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）：

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）：

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）：

网络平台

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

https://pubmed.ncbi.nlm.nih.gov/

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：

填写病例记录表，Resman管理系统

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

CRF and ResMan

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2023-03-27 12:35:38