ChiCTR2000031980 版本V2.8 版本创建时间2020/05/01 09:25:44 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：

 ChiCTR2000031980 

最近更新日期：

Date of Last Refreshed on：

 2020-04-16 23:28:27 

注册时间：

Date of Registration：

 2020-04-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

石玮医师：请尽快上传伦理审批文件并填写伦理审批日期。 中药（黄芪/三七）联合新型溶瘤病毒/融合细胞疫苗增强免疫细胞抗癌技术治疗晚期肝癌和肺癌的前瞻性、随机、对照临床研究

Public title：

A prospective, randomized and controlled clinical study of traditional Chinese medicine (Astragalus / Panax notoginseng) combined with a new oncolytic virus / fusion cell vaccine in the treatment of advanced liver cancer and lung cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

中药（黄芪/三七）联合新型溶瘤病毒/融合细胞疫苗增强免疫细胞抗癌技术治疗晚期肝癌和肺癌的前瞻性、随机、对照临床研究

Scientific title：

A prospective, randomized and controlled clinical study of traditional Chinese medicine (Astragalus / Panax notoginseng) combined with a new oncolytic virus / fusion cell vaccine in the treatment of advanced liver cancer and lung 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：

ChiMCTR2000003215

申请注册联系人：

石玮 

研究负责人：

石玮 

Applicant：

Wei Shi 

Study leader：

Wei Shi 

申请注册联系人电话：

Applicant telephone：

 +86 18978885787

研究负责人电话：

Study leader's
telephone：

+86 18978885787

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：

 35111747@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 35111747@qq.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：

广西南宁仙葫经济开发区仙葫大道

研究负责人通讯地址：

广西南宁青秀区东葛路89-9号

Applicant address：

Xianhu Avenue, Xianhu Economic Development Zone, Nanning, Guangxi

Study leader's address：

89-9 Dongge Road, Qingxiu District, Nanning, Guangxi

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：

广西中医药大学第一附属医院

Applicant's institution：

The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine

研究负责人所在单位：

广西中医药大学第一附属医院

Affiliation of the Leader：

The First Affiliated Hospital of Guangxi University 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：

 伦审2020-009-02

伦理委员会批件附件：

Approved file of Ethical Committee：

批准本研究的伦理委员会名称：

广西中医药大学第一附属医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine

伦理委员会批准日期：

Date of approved by ethic committee：

 1990-01-01 00:00:00

伦理委员会联系人：

方芳

Contact Name of the ethic committee：

Fang Fang

伦理委员会联系地址：

广西南宁青秀区东葛路89-9号

Contact Address of the ethic committee：

89-9 Dongge Road, Qingxiu District, Nanning, Guangxi

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：

广西中医药大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Guangxi University of traditional Chinese Medicine

研究实施负责（组长）单位地址：

广西南宁青秀区东葛路89-9号

Primary sponsor's address：

89-9 Dongge Road, Qingxiu District, Nanning, Guangxi

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

广西

市(区县)：

南宁

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

Nanning

单位(医院)：

广西中医药大学第一附属医院

具体地址：

仙葫经济开发区仙葫大道

Institution
hospital：

The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine

Address：

Xianhu Avenue, Xianhu Economic Development Zone

经费或物资来源：

国家科技重大专项重大新药创新项目

Source(s) of funding：

Major new drug innovation projects of major national science and technology projects

研究疾病：

肺癌、肝癌、各种恶性肿瘤  

Target disease：

Lung cancer, liver cancer、Various malignant tumors

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：

 探索性研究/预试验 

Study phase：

0

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

观察中药（黄芪/三七）联合新型溶瘤病毒/融合细胞增强免疫细胞抗晚期肝癌、肺癌等恶性肿瘤的安全性、耐受性和有效性。  

Objectives of Study：

To observe the safety, tolerance and effectiveness of traditional Chinese medicine (Astragalus / Panax notoginseng) combined with new oncolytic virus / fusion cells to enhance the immune cells against advanced liver cancer, lung cancer and other malignant tumors.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

肝癌入选标准
1）年龄在 18 至75岁，性别不限；
2）经组织/细胞学确诊的晚期肝细胞肝癌（不可手术或转移性）并缺乏标准治疗或不具备标准治疗条件的患者；
3）Child-pugh肝功能评级：A级、B级；
4）有至少一个可测量病灶（按RECIST1.1标准）；
5）入组前患者接受上一次抗肿瘤治疗后至少4周或大于5个半衰期；手术治疗大于3个月；末次介入治疗结束时间大于1月；
6）预期生存时间≥3月；
7）终末期肝病模型（MELD）评分＜9分；
8）能合作观察不良事件和疗效；
9）无其他抗肿瘤伴随治疗（包括类固醇药物）；
10）ECOG 评分≤2；
11）血清白蛋白≥30g/L，血清ALT≤190U/L，AST≤200 U/L，血清TBIL≤1.5×ULN，电解质正常或经过治疗后达到正常，蛋白尿=0~1+，血肌酐≤1.5×ULN；
12）血常规检查标准需符合：HB≥ 80g/L；ANC≥1.5×10^9/L；PLT ≥70×10^9/L；
13）患者自愿签署书面知情同意书。
肺癌纳入标准
1）自愿参加本次临床试验，理解研究程序且已签署知情同意；
2）年龄：18~75 周岁的男性或女性患者；
3）组织学或细胞学确诊的局部晚期或转移性小细胞或非小细胞肺癌患者，
4）按东部肿瘤合作组织（ECOG）标准，体能状态为0~2分；
5）预期生存期不少于3个月；
6）根据RECIST1.1版实体肿瘤疗效评价标准，患者至少有一处影像学（CT、MRI）可测量病灶，要求最长径≥10 mm（若为淋巴结，则要求短轴≥15mm）（脑转移病灶不作为唯一可测量病灶）；
7）受试者必须具有适当的器官功能，入组前符合下列实验室检查结果：骨髓储备基本正常：中性粒细胞绝对计数≥1.5×10^9/L ，血小板 ≥100×10^9/L ，以及血红蛋白≥80g/L；肝脏功能基本正常：血清中白蛋白≥3.0 g/dL ；胆红素≤1.5 ×ULN ，ALT 和AST ≤2.5 ×ULN ，如有肝转移，则ALT 或AST≤5×ULN；肾功能正常：肌酐≤1.5 ×ULN或24 小时肌酐清除率≥60 mL/min；凝血功能基本正常：INR≤1.5 ×ULN ，APTT ≤1.5 ×ULN ；心脏功能：左心室射血分数≥50%；心电图基本正常，QT 间期男性≤450 ms，女性≤470 ms；
8）患者必须从之前的治疗毒性中恢复至≤1级，除了脱发和2级既往含铂治疗相关神经病变（CTC AE 5.0）。

Inclusion criteria

Inclusion criteria of liver cancer
1) The age is from 18 to 75 years old, gender is not limited;
2) Late stage HCC (non operative or metastatic) confirmed by histology / cytology and lack of criteria patients who are treated or do not have standard treatment conditions;
3) Child Pugh liver function rating: A, B;
4) There is at least one measurable focus (according to the recist1.1 standard);
5) At least 4 weeks or more than 5 half-lives after the last anti-tumor treatment; surgical treatment more than 3 months; the end time of the last interventional therapy was more than 1 month;
6) Expected survival time >= 3 months;
7) The MELD score was less than 9;
8) Can cooperate to observe adverse events and curative effect;
9) No other anti-tumor concomitant treatment (including steroid drugs);
10) ECoG score <= 2;
11) Serum albumin >= 30g / L, ALT <= 190u / L, AST <= 200u / L, serum TBIL <= 1.5 x ULN, electrolyte normal or normal after treatment, proteinuria = 0 ~ 1 +, blood creatinine <= 1.5 × ULN;
12) The blood routine examination standard should be: HB >= 80g / L; ANC >= 1.5 x 10^9 / L; PLT >= 70 x 10^9/L;
13) Patients voluntarily sign written informed consent.
Inclusion criteria of lung cancer
1) Voluntarily participate in the clinical trial, understand the research procedure and have signed the informed consent;
2) Age: male or female patients aged 18-75 years;
3) Patients with locally advanced or metastatic small cell or non-small cell lung cancer confirmed by histology or cytology;
4) According to the standard of ECoG, the physical condition was 0-2 points;
5) The expected life span is not less than 3 months;
6) According to recist1.1 evaluation standard of solid tumor efficacy, patients have at least one imaging (CT, MRI) can measure the focus, the longest diameter is required to be >= 10 mm (in case of lymph nodes, the short axis is required to be >= 15 mm) (brain metastasis is not the only measurable lesion);
7) The subjects must have proper organ function and meet the following laboratory test results before entering the group: Bone marrow reserve is basically normal: neutrophil absolute count >= 1.5 x 10^9 / L, platelet >= 100 x 10^9 / L, and hemoglobin >= 80g / L; Liver function is basically normal: albumin in serum >= 3.0 g / dl; bilirubin <= 1.5 x ULN, ALT and Ast <= 2.5 x ULN, ALT or AST <= 5 x ULN in case of liver metastasis; Normal renal function: creatinine <= 1.5 x ULN or creatinine clearance rate >= 60 ml / min in 24 hours; Coagulation function is basically normal: INR <= 1.5 x ULN, APTT <= 1.5 x ULN; Cardiac function: left ventricular ejection fraction >= 50%; ECG is basically normal, QT interval in men <= 450 ms, female <= 470 MS;
8) The patient must recover from the previous treatment toxicity to <= level 1, except for alopecia and previous platinum containing treatment of level 2 related neuropathy (CTC AE 5.0);

排除标准：

肝癌排除标准
1）严重肝硬化，肝萎缩，门静脉高压，中等量以上腹水；
2）既往有肝移植病史；
3）弥漫型肝癌，门静脉主干出现癌栓或肝阻塞性黄疸以及肝功能衰竭，出现难以控制的肝性脑病；
4）二重癌及多重癌患者；
5）有活动性上消化道溃疡、明显呕吐、慢性腹泻、肠梗阻、吸收障碍等或其他已知会影响药物吸收、分布、代谢或清除的患者；
6）之前抗癌治疗的毒性反应尚未恢复至I级或尚未从之前的手术中完全恢复；
7）有活动性出血或凝血功能异常（PT>16s、APTT>43s、TT>21s、INR≥2）、具有出血倾向或正在接受溶栓或抗凝治疗；
8）同时服用可能延长QTc和/或 Tdp的药物或影响药物代谢的药物（如镇静剂）；
9）疑似对黄芪/三七、溶瘤病毒或同类药物及其代谢物或其药用辅料有过敏史者；
10）怀孕或者哺乳期女性患者，或试验期间不愿意避孕者；
11）任何显著的临床和实验室异常，研究者认为影响安全性评价者；
12）脑转移、脑膜转移或各种精神障碍者；
13）肾小球滤过率明显异常者（内生肌酐清除率<60ml/min，血清肌酐≥1.5×ULN）；
14）正在接受广谱抗病毒药物治疗，如金刚烷胺、阿昔洛韦、更昔洛韦、利巴韦林等；抗乙肝病毒治疗患者需停药3天；
15）自身免疫疾病者；
16）HIV、HCV、HDV感染者；
17）在试验前3月内参加了任何药物或医疗器械临床试验者。
肺癌排除标准
1）对黄芪/三七及其代谢物或其药用辅料（不论有没有活性）有过敏史者；
2）在首次给药前30 天内服用过其他正在临床试验的药物；
3）除了肺癌之外，近5年内还被诊断有另外一种恶性肿瘤者（不包括已经治愈的恶性肿瘤，如完全切除的基底细胞癌和原位癌）；
4）首次使用研究药物之前2周内接受过重大外科治疗、切开活检或明显创伤性损伤者。在所有情况下，患者必须在治疗开始前充分恢复及稳定；
5）受试者具有活动性胃肠道疾病或其他疾病可能导致明显影响药物吸收分布，代谢或排泄的因素；
6）无法控制的慢性系统性合并疾病（如严重的慢性肺部，肝脏，肾脏或心脏疾病）；
7）按NYHA标准，III~IV 级心功能不全者；
8）基线期心电图QTc 延长者（QTcF：男性>450 ms，女性>470 ms）；
9）任何无法控制的严重的与临床研究相关的问题（例如不受控制的精神病状态，不能控制的胸腔积液和/或心包积液，不受控的并发症，包括活动性感染、动脉血栓形成和症状性肺栓塞）；
10）存在间质性肺病、药物诱导的间质性肺病、需要类固醇治疗的放射性肺炎的既往病史，或者任何临床活性期间质性肺病证据；
11）受试者正处于急性感染期并需要药物治疗、抗病毒治疗；
12）受试者HIV、HBV 和HCV检测阳性（HBV病毒拷贝数≧104拷贝/mL，HCV病毒拷贝数≧103拷贝/mL）；
13）经研究者判断，客观条件（包括患者心理状态，家庭关系，社会因素或地域因素等）使患者无法完成计划研究的或受试者有其他可能导致本研究被迫中途终止的因素；
14）妊娠期或哺乳期女性；
15）自身免疫疾病。

Exclusion criteria：

Exclusion criteria for liver cancer
1) Severe cirrhosis, liver atrophy, portal hypertension, ascites of medium or more quantity;
2) Previous history of liver transplantation;
3) Diffuse liver cancer, tumor thrombus or liver obstructive jaundice in the main portal vein, and liver failure, it is difficult to control hepatic encephalopathy;
4) Double cancer and multiple cancer patients;
5) Active upper gastrointestinal ulcer, obvious vomiting, chronic diarrhea, intestinal obstruction, absorption disorder , etc.. Other patients known to affect drug absorption, distribution, metabolism or clearance;
6) The toxicity of previous anticancer therapy has not been restored to level I or completely recovered from previous surgery;
7) Active bleeding or abnormal coagulation (PT > 16S, APTT > 43S, TT > 21s, INR >= 2), with bleeding tendency or undergoing thrombolysis or anticoagulation treatment;
8) Taking drugs that may prolong QTc and / or TDP or affect drug metabolism (such as sedation agent) at the same time;
9) Suspected allergy to Astragalus / Panax notoginseng, oncolytic virus or similar drugs and their metabolites or their pharmaceutical accessories;
10) Pregnant or lactating women, or those who are unwilling to use contraception during the trial;
11) Any significant clinical and laboratory abnormalities that the investigator considers to affect the safety assessment;
12) Brain metastasis, meningeal metastasis or various mental disorders;
13) Glomerular filtration rate was significantly abnormal (creatinine clearance rate < 60ml / min, serum creatinine
>= 1.5 x ULN);
14) They are receiving broad-spectrum antiviral drugs, such as amantadine, acyclovir, ganciclovir and lidocaine bavelin, et al. 3 days of discontinuation of Antihepatitis B treatment;
15) Autoimmune diseases;
16) HIV, HCV, HDV infection;
17) Those who participated in clinical trials of any drugs or medical devices within 3 months before the trial.
Exclusion criteria for lung cancer
1) Those who have a history of allergy to Astragalus / notoginseng and their metabolites or their pharmaceutical excipients (with or without activity);
2) Have taken other drugs in clinical trials within 30 days before the first administration;
3) In addition to lung cancer, in the past five years, there has been a diagnosis of another kind of malignant tumor (excluding those already treated malignant tumors, such as completely resected basal cell carcinoma and carcinoma in situ;
4) Major surgical treatment, open biopsy or significant trauma within 2 weeks prior to first use of study drug. In all cases, the patient must be fully recovered and stable before treatment;
5) Subjects with active gastrointestinal disease or other diseases may significantly affect drug absorption, metabolic or excretory factors;
6) Uncontrollable chronic systemic complications (such as severe chronic lung, liver, kidney, heart or visceral diseases);
7) According to NYHA standard, patients with grade III-IV cardiac insufficiency;
8) QTc of baseline ECG was prolonged (QTCF: male > 450 ms, female > 470 MS);
9) Any uncontrollable serious clinical research related problems (such as uncontrolled psychosis state, uncontrolled pleural effusion and / or pericardial effusion, uncontrolled complications, including mobility infection, arterial thrombosis and symptomatic pulmonary embolism;
10) Presence of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid treatment previous medical history, or evidence of any qualitative lung disease during clinical activity;
11) The subjects were in the stage of acute infection and needed drug treatment and antiviral treatment;
12) HIV, HBV and HCV were positive in the subjects (number of copies of HBV >= 104 copies / ml, copy number of HCV >= 10^3 copies / ml);
13) According to the judgment of the researcher, the objective conditions (including patients' psychological state, family relationship, social factors or place domain factors, etc.) make the patients unable to complete the planned study or the subjects have other factors that may cause the study to be factors of forced termination;
14) Pregnant or lactating women;
15) Autoimmune diseases.

研究实施时间：

Study execute time：

从 From 2020-04-01 00:00:00至 To 2022-04-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-04-01 00:00:00 至 To 2022-01-31 00:00:00

干预措施：

Interventions：

组别：

晚期恶性实体肿瘤

样本量：

 20

Group：

Advanced malignant solid tumor

Sample size：

干预措施：

新型溶瘤病毒治疗，剂量：1～3×10^7～10 pfu/kg，视病情可静脉注射，或腹腔注射、瘤内注射，也可以同时注射，每周1次，一个周期为8～12周，根据康复状况决定是否增加治疗时间。

干预措施代码：

Intervention：

Novel oncolytic virus treatment, dose: 1–3 × 10^7–10 pfu/kg. Depending on clinical status, the virus may be administered intravenously, intraperitoneally, or intratumorally, alone or in combination. Treatment is administered once weekly for 8 to 12 weeks per cycle, with treatment duration adjusted according to clinical response and recovery.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广西 

市(区县)：

 南宁 

Country：

China

Province：

Guangxi

City：

Nanning

单位(医院)：

 广西中医药大学第一附属医院 

单位级别：

 三级甲等 

Institution
hospital：

The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全性指标

指标类型：

主要指标

Outcome：

Safety index

Type：

Primary indicator

测量时间点：

每3～4周1次

测量方法：

与研究药物有关不良反应的发生率

Measure time point of outcome：

Once every 3–4 weeks

Measure method：

Incidence of treatment-related adverse events

指标中文名：

肿瘤进展时间

指标类型：

次要指标

Outcome：

Time to progression, TTP

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观有效率

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：

症状缓解率

指标类型：

次要指标

Outcome：

Symptom relief 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：

生活质量

指标类型：

次要指标

Outcome：

Quality of life

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 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）：

本随机方法由负责人编制随机分配卡

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

In this random method, the person in charge prepares the random distribution card.

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：

开放

Blinding：

open-label

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

是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）：

原始数据上报国家科技部系统共享

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

Not stated

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：

数据采集 研究病历为最原始记录，必须妥善保存。本研究采用电子病例报告表进行数据的采集。病例报告表来自研究病历，由研究者完成。每个筛选和入选病例必须完成病例报告表。研究者将确保数据采集的准确性和可靠性。所有数据都将采用基于因特网的电子CRF加以记录，在线自动检查数据的完整性。输入用户名和密码后可获取研究数据，用户应严格保密自己的密码。服务器和用户个人电脑之间的电子通讯是加密的，不会传输被保护的数据(患者姓名、地址、身份证号等)。对于研究数据的所有更改，可获得完整的审核跟踪。实验室数据将采用取决于中心和性别的正常值范围加以确认。描述性和逻辑性数据检查在不断完善的数据库中进行，任何不合理或不一致的数据输入将告知研究单位和/或监查人员，由研究单位的工作人员加以解释和纠正。研究者必须对患者毒性反应分级及肿瘤疗效反应作出决定，而主要研究者应该对诊断作出最后判断。在研究过程中，研究者应允许申办方的监查人员或代表到研究机构检查研究相关文件(如病人知情同意书、研究药物清点表、伦理委员会的批准文件)。监查人员到访时会对病人的档案进行严格审阅，以核对记录在病例报告表(CRF)的信息，尤其是安全性和疗效有关的关键信息和病人的原始记录是否吻合。 数据管理 1、管理 （1）建立数据管理委员会，招聘熟练计算机操作人员组建数据管理委员会，由本课题组成员担任组长，其余数据管理人员均对该研究方案不知情。 （2）数据保存与录入所有受试者数据及量表资料由DDC组员进行电脑录入，将原始资料全部录入保存在课题数据库，该数据库录入内容与原始资料保持一致。纸质资料专人管理。 （3）数据质控与备份课题组成员定期对录入数据进行质控，及时报告、记录数据缺失项，对明显错误数据重新核对、校准。定期导出、备份数据至物理存储装置，专人保管，防治数据库损坏。

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

data acquisition The research medical record is the most original record and must be kept properly. In this study, electronic case report form was used to collect data. The case report form is from the study medical record and completed by the investigator. The case report form must be completed for each screened and selected case. Researchers will ensure the accuracy and reliability of data collection. All data will be recorded by Internet based electronic CRF, and the integrity of data will be checked automatically online. After entering the user name and password, the research data can be obtained, and the user should keep his password strictly confidential. The electronic communication between the server and the user's personal computer is encrypted, and the protected data (patient name, address, ID number, etc.) will not be transmitted. A complete audit trail is available for all changes to study data. Laboratory data will be confirmed using a range of normal values depending on the center and gender. Descriptive and logical data check is carried out in the constantly improved database. Any unreasonable or inconsistent data input will be informed to the research unit and / or the inspector, and the staff of the research unit will explain and correct it. The researchers must make a decision on the classification of toxic reactions and the response of tumor efficacy, and the main researchers should make a final judgment on the diagnosis. During the research process, the investigator shall allow the sponsor's inspectors or representatives to inspect the research related documents (such as the informed consent of patients, the inventory of research drugs, and the approval documents of the ethics committee) in the research institution. During the visit, the inspectors will strictly review the patient's files to check whether the information recorded in the CRF, especially the key information related to safety and efficacy, is consistent with the original record of the patient. data management 1, management (1) Establish a data management committee, recruit skilled computer operators to establish a data management committee, with the members of the research group as the team leader, and the rest of the data management personnel are unaware of the research scheme. (2) Data saving and inputting all subjects' data and scale data shall be input by DDC team members by computer, and all the original data shall be input and saved in the subject database, and the input content of the database shall be consistent with the original data. Paper materials shall be managed by special personnel. (3) The members of the data quality control and backup research group regularly control the input data, timely report and record the missing items of the data, and recheck and calibrate the obviously wrong data. Regularly export and backup the data to the physical storage device, and assign special personnel to keep it to prevent database damage.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-04-16 22:27:52