ChiCTR2000035399 版本V1.1 版本创建时间2020/08/12 15:59:56 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：

ChiCTR2000035399 

最近更新日期：

Date of Last Refreshed on：

2020-08-10 22:21:54 

注册时间：

Date of Registration：

2020-08-10 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

审核中（六）崔越宏医师：该研究尚未获得伦理委员会批准，请于批准后再开始纳入参试者，并与我们联系上传批件。 T细胞受体（TCR）免疫组库信息预测肿瘤免疫联合抗血管生成治疗毒副反应及疗效的真实世界研究

Public title：

A real world study of T cell receptor repertoire sequencing information to predict side-effects and efficacy of cancer immunotherapy combined with anti-angiogenesis treatment.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

T细胞受体（TCR）免疫组库信息预测肿瘤免疫联合抗血管生成治疗的毒副反应及疗效

Scientific title：

T cell receptor repertoire sequencing information to predict side-effects and efficacy of cancer immunotherapy combined with anti-angiogenesis treatment.

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：

崔越宏 

研究负责人：

崔越宏 

Applicant：

Cui Yuehong 

Study leader：

Cui Yuehong 

申请注册联系人电话：

Applicant telephone：

+8613916912156

研究负责人电话：

Study leader's telephone：

+8613916912156

申请注册联系人传真 ：

Applicant Fax：

021-52303355

研究负责人传真：

Study leader's fax：

021-52303355

申请注册联系人电子邮件：

Applicant E-mail：

cui.yuehong@zs-hospital.sh.cn

研究负责人电子邮件：

Study leader's E-mail：

cui.yuehong@zs-hospital.sh.cn

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

www.zs-hospital.sh.cn

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

www.zs-hospital.sh.cn

申请注册联系人通讯地址：

上海市枫林路180号

研究负责人通讯地址：

上海市枫林路180号

Applicant address：

Fenglin Road 180#, Shanghai, China

Study leader's address：

Fenglin Road 180#, Shanghai, China

申请注册联系人邮政编码：

Applicant postcode：

200032

研究负责人邮政编码：

Study leader's postcode：

200032

申请人所在单位：

复旦大学附属中山医院

Applicant's institution：

Zhongshan Hospital, Fudan University

研究负责人所在单位：

复旦大学附属中山医院

Affiliation of the Leader：

Zhongshan Hospital, Fudan University

是否获伦理委员会批准：

否/No

Approved by ethic committee：

No

伦理委员会批件文号：

Approved No. of ethic committee：

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：

Name of the ethic committee：

伦理委员会批准日期：

Date of approved by ethic committee：

2013-08-26 00:00:00

伦理委员会联系人：

Contact Name of the ethic committee：

伦理委员会联系地址：

Contact Address of the ethic committee：

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：

复旦大学附属中山医院

Primary sponsor：

Zhongshan Hospital, Fudan University

研究实施负责（组长）单位地址：

上海市枫林路180号

Primary sponsor's address：

Fenglin Road 180#, Shanghai, 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)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

复旦大学附属中山医院

具体地址：

枫林路180号

Institution
hospital：

Zhongshan Hospital, Fudan University

Address：

180 Fenglin Road

经费或物资来源：

科研经费

Source(s) of funding：

Scientific Foundation

Target disease：

stomach adenocarcinoma and esophageal squamous cell carcinoma

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

队列研究 

Study design：

Cohort study 

研究目的：

主要研究目的 1）不可切除或转移性胃腺癌或食管鳞癌患者中，PD-1单抗联合抗血管生成药物作为二线及以上治疗的肿瘤客观缓解率（ORR） 和毒副反应发生率。 2）分析TCR免疫组库信息动态变化与疗效和毒副反应的相关性。 次要研究目的 1）PD-1单抗联合抗血管生成药物作为不可切除或转移性胃腺癌或食管鳞癌患者二线及以上治疗可获得的无进展生存时间（PFS）和总生存时间（OS）。 2）PD-1单抗联合抗血管生成药物作为不可切除或转移性胃腺癌患者或食管鳞癌二线及以上治疗的疾病控制率（DCR）。 探索性研究目的 1）探索在“PD-1单抗联合抗血管生成药物”治疗前：组织标本行NGS检测，寻找敏感突变位点。 2）取三个时间点的外周血标本：基线、最佳缓解时和疾病进展时，分析TCR免疫组库信息相关指标： ① Evenness（均一性）；② Shannon Diversity（Shannon多样性）；③ Clone Gini index（克隆基尼指数：该值越低，表示克隆多样性越高）；④ DE50 (多样均一性，综合评估Evenness和Diversity)；⑤ Convergent TCR (TCR聚集度)。  

Objectives of Study：

Primary Endpoint 1）The ORR and safety in patients with unresectable or metastatic stomach adenocarcinoma or esophageal squamous cell carcinoma patients treated with anti-angiogenesis agents in combination with PD-1 inhibitor as a second-line or later treatment. 2) The relationship of efficacy and side-effects with T cell receptor repertoire sequencing information. Secondary Endpoints 1) PFS, OS 2) DCR Exploratory Endpoints 1) Next-generation sequencing (NGS) of tissue (collected prior intervention) to explore find sensitive mutation sites correlated to anti-angiogenesis agents and PD-1 inhibitor combination treatment. 2) Peripheral blood specimens taken at three time points: baseline, optimal response time and disease progression, analyze the following indicators: ① Evenness ② Shannon Diversity ③ Clone Gini index ④ DE50 ⑤ Convergent TCR

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) 患者自愿参加研究，签署同意书，有良好的依从性，并服从随访，乐于且能够遵守研究期间的方案。
2) 男性或女性，年龄≥18岁且≤75岁。
3) 美国东部肿瘤协作组的体能状态评分（ECOG PS）评分为0或1。
4) 组织学和/或细胞学确认不可切除的或转移性的胃腺癌或食管鳞癌患者。
5) 患者既往一线或二线标准治疗失败，具有可测量的靶病灶，且未曾接受过针对靶病灶的放疗等局部治疗（注：之前接受过放疗的病灶不可以视为靶病灶，除非放疗后病灶发生明确进展）。
6) 使用0或1种降压药物即可有效控制血压，定义为随机前收缩压≤140mmHg，舒张压≤90mmHg，且在随机前一周内没有更换降压药物。
7) 适当的骨髓储备，表现为受试者入组前7天内血常规符合下列标准：血红蛋白≥90g/L；中性粒细胞绝对计数（ANC）≥1.5×109/L；血小板≥90×109/L（患者在采集血样2周内未接受过输血或生长因子支持）。
8) 适当的肝功能，表现为符合下列所有要求：
a. 血清总胆红素≤1.5倍正常上限值(ULN)（Gilbert综合征患者若总胆红素<3倍ULN则可以入组，胆道梗阻者允许胆道引流）；
b. 血清白蛋白≥30g/L;
c. AST、ALT≤3倍ULN（如存在肝转移则AST和ALT允许≤5倍ULN）。
9) 适当的肾功能，表现为符合下列所有要求：
a．血清肌酐≤1.5倍ULN且肌酐清除率≥50ML/min（使用Cockcroft-Gault公式）；
b. 蛋白尿＜2+；如果蛋白尿≥2+，则24小时尿蛋白必须＜2g。
10) 国际标准化比值（INR）或凝血酶原时间（PT）≤1.5倍ULN，活化部分凝血活酶时间（APTT）≤1.5倍ULN；无应用抗凝剂治疗病史；研究者判断无高凝风险。
11) 既往抗癌治疗或外科手术的所有急性毒性作用缓解为NCI-CTCAE 5.0版本≤1级（除脱发或根据研究者判断认为对患者的安全没有风险的其他毒性作用）。
12) 具有生育能力的女性必须在入组前7天内的尿液或血清妊娠检测为阴性，并且须同意在研究期间以及研究结束后6个月内采取高效的避孕措施；未绝育的男性须同意在研究期间以及研究结束后6个月内采取高效的避孕措施，并且同意在该相同时间段内避免捐献精子。
13) 有自主行为能力，有吞咽药片的能力，无影响口服药物吸收的胃肠道疾病。
14) 同意提供血液学及组织学样本。

Inclusion criteria

1) The patient volunteers to participate in the study, signs a consent form, has good compliance, and obeys the follow-up, and is willing and able to follow the protocol during the study.
2) Male or female, aged ≥18 years and ≤75 years.
3) The ECOG PS score is 0 or 1.
4) Histological and/or cytological confirmation of patients with unresectable or metastatic gastric adenocarcinoma or esophageal squamous cell carcinoma.
5) Patients have failed previous first-line standard treatments, have measurable target lesions, and have not received local treatments such as radiotherapy for target lesions (Note: lesions that have previously received radiation therapy cannot be considered target lesions, except that after radiation therapy, clear progress has occurred).
6) The use of 0-1 antihypertensive drug can effectively control blood pressure, which is defined as random pre-systolic blood pressure ≤140mmHg, diastolic blood pressure ≤90mmHg, and no antihypertensive drug has been changed within one week before randomization.
7) Appropriate bone marrow reserve, as shown in the blood count of the subject within 7 days before enrollment: hemoglobin ≥90g / L; ANC ≥1.5 × 109 / L; platelet ≥90 × 109 / L (patients have not received blood transfusion or growth factor support within 2 weeks prior blood collection).
8) Appropriate liver function is shown to meet all of the following requirements:
a. Serum total bilirubin ≤ 1.5 x ULN (Gilbert syndrome patients can be included if the total bilirubin is <3 x ULN, and those with biliary obstruction allow biliary drainage);
b. serum albumin ≥30g / L;
c. AST, ALT ≤ 3 x ULN (If liver metastases exist, AST and ALT allow ≤ 5 x ULN).
9) Appropriate renal function demonstrated by all of the following requirements:
a. Serum creatinine ≤ 1.5 x ULN and creatinine clearance ≥ 50ml/min (using Cockcroft-Gault formula);
b. Proteinuria <++; if proteinuria is ≥++, 24-hour urine protein must be <2g.
10) INR or prothrombin time (PT) ≤ 1.5 x ULN, APTT ≤ 1.5 x ULN; no history of anticoagulant treatment; investigator judges no high coagulation risk.
11) All acute toxic effects of previous anti-cancer treatment or surgery were all relieved by NCI-CTCAE version 5.0 ≤ 1 (except for hair loss or other toxic effects that the investigator judges to have no risk to the patient's safety).
12) Fertile women must have a negative urine or serum pregnancy test within 7 days before enrollment, and must agree to use effective contraception during the study period and within 6 months after the end of the study period; non-sterile men must agree to use efficient contraception during the study period and within 6 months after the study was completed. Patient agrees to avoid sperm donation during the same time period.
13) Have the ability to act autonomously, have the ability to swallow pills, and have no gastrointestinal diseases that affect oral drug absorption.
14) Agree to provide hematology and histology samples.

排除标准：

1) 患有未分化的或其它组织学类型的胃癌或食管癌；影像学检查发现存在肿瘤侵犯主要血管的证据（包括完全邻近、围绕或延伸至主要 血管腔内，例如肺动脉或上腔静脉），且研究者判断不适合入组。
2) 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。
备注：以下疾病的患者不被排除，可以进入进一步筛选：
a. 控制的1型糖尿病
b. 甲状腺机能减退（如果仅用激素替代疗法可以控制）
c. 控制的乳糜泻
d. 无需全身治疗的皮肤病（例如白癜风，牛皮癣，脱发）
e. 其它任何在没有外部触发因素的情况下预期不会复发的疾病
3) 2年内有任何活动性恶性肿瘤，除外本试验中正在研究的特定癌症以及已经治愈的局部复发性癌症（如已切除的基底细胞或鳞状细胞皮肤癌，浅表膀胱癌，宫颈或乳腺原位癌）。
4) 入组前 7 天内存在不可控制的、需要频繁引流的胸腔积液、心包积液或腹水（允许积液细胞学检查确认）。
5) 入组前两周内有消化道出血，或经研究者判断具有高出血风险者（注：单纯粪便潜血(+)不是排除标准）。
6) 入组前6个月内曾发生胃肠穿孔和/或瘘管。
7) 患者存在不能吞咽、恶心呕吐、上消化道梗阻、生理功能异常、吸收不良综合征等，可能影响口服药物吸收者。
8) 入组前2个月内体重下降≥ 20%。
9) 有以下疾病病史：间质性肺病、非感染性肺炎或不可控的全身疾病包括糖尿病、高血压、肺纤维化、急性肺病等。
10) 需要给予全身抗细菌药、抗真菌药或抗病毒治疗的重度慢性或活动性感染，包括结核感染等。
11) 已知有HIV感染史。
12) 未治疗的慢性乙型肝炎或慢性 HBV 携带者，若乙型肝炎病毒（HBV）DNA 超过ULN、或丙型肝炎病毒（HCV）RNA 阳性患者应排除。
13) 有以下任何心血管风险因素：
a. 在入组前≤ 28 天内出现心源性胸痛，定义为限制日常生活器具性活动的中度痛。
b. 入组前≤ 28天内曾出现有症状的肺栓塞。
c. 入组前≤ 6个月内曾发生急性心肌梗塞。
d. 入组前≤ 6个月内有达到纽约心脏病协会Ⅲ/IV级的任何心力衰竭史，或左心射血分数<50%。
e. 入组前≤ 6个月内曾发生≥2级的室性心律失常。
f. 入组前≤ 6个月内曾发生脑血管意外（CVA）
g. 患有高血压且经降压药物治疗无法获得良好控制者，表现为：收缩压>140 mmHg，舒张压>90 mmHg（3个月内）。
h. 显著心脏传导异常，包括QTc间期延长综合征病史（QTc间期延长>450 ms）和/或起 搏器植入史。
14) 筛选时和研究期间出于治疗目的需要使用标准剂量的口服或肠外抗凝药物或溶栓药物。
15) 患者有脑转移或脑膜转移。
16) 对任何研究用药成份过敏者。
17) 曾进行异基因干细胞移植或者器官移植。
18) 在入组前≤ 14 天内需要用皮质类固醇（剂量高于 10 mg/d的强的松或同类药物同
等剂量）或其它免疫抑制剂全身治疗的患者。
备注：目前或之前曾使用过以下任何类固醇方案的患者可以入选：
a. 肾上腺素替代性类固醇（强的松≤10mg/d或同类药物同等剂量）
b. 全身吸收量极小的局部、眼用、关节内、鼻内和吸入性皮质类固醇。
c. 短期（≤ 7 天）使用皮质类固醇，用于预防（例如，用于预防造影剂过敏或针对
特定化疗的止吐剂）或用于治疗非自身免疫病症（例如由接触性过敏原引起的延迟型超敏反应）。
19) 在随机之前4周内曾接种活疫苗（备注：季节性流感疫苗通常是灭活疫苗，允许使用。鼻腔内使用的疫苗是活疫苗，不允许使用） 。
20) 在入组前28天内或5个半衰期内（以更短者为准，但至少14天）曾接受：免疫治疗（如白介素、干扰素、胸腺素等）或任何试验治疗。
21) 曾接受抗PD-1、抗PD-L1、抗PD-L2或任何其它特定靶向T细胞共刺激或检查点通路的抗体或药物治疗。
22) 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。
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。

Exclusion criteria：

1) Have undifferentiated or other histological types of gastric or esophageal cancer; evidence of tumor invasion of major blood vessels (including completely adjacent, surrounding, or extending into the main vessel lumen, such as the pulmonary artery or superior vena cava) , and the researcher judges that it is not suitable for enrollment.
2) Patients with active autoimmune disease or a history of autoimmune disease but who may relapse.
Note: Patients with the following diseases are not excluded and can be entered for further screening:
a. Controlled Type 1 Diabetes
b. Hypothyroidism (if only controlled by hormone replacement therapy)
c. Controlled celiac disease
d. Skin diseases that do not require systemic treatment (e.g. vitiligo, psoriasis, hair loss)
e. Any other disease that is not expected to recur without external triggers
3) Any active malignant tumor within 2 years, except for the specific cancer being studied in this trial and cured local recurrent cancer (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ).
4) There is uncontrollable pleural effusion, pericardial effusion, or ascites that need to be drained frequently within 7 days before enrollment (allow effusion cytology to confirm).
5) Patients with gastrointestinal bleeding within two weeks before enrollment, or those at high risk of bleeding as judged by the investigator (Note: fecal occult blood (+) is not an exclusion criterion).
6) Gastrointestinal perforation and / or fistula occurred within 6 months before enrollment.
7) There are many factors that affect oral drug absorption (such as inability to swallow, nausea and vomiting, upper gastrointestinal obstruction, abnormal physiological function, malabsorption syndrome, etc.), which may affect anlotinib hydrochloride absorbers.
8) Weight loss ≥ 20% within 2 months before enrollment.
9) History of the following diseases: interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc.
10) Severe chronic or active infections, including tuberculosis, that require systemic antibacterial, antifungal or antiviral treatment.
11) Known history of HIV infection.
12) Patients with untreated chronic hepatitis B or chronic HBV carriers with hepatitis B virus (HBV) DNA exceeding ULN, or hepatitis C virus (HCV) RNA positive should be excluded. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable patients with hepatitis B (HBV DNA 13) Have any of the following cardiovascular risk factors:
a. Cardiogenic chest pain occurs within ≤ 28 days prior to enrollment, and is defined as moderate pain that limits the daily use of appliance sexual activity.
b. Symptomatic pulmonary embolism occurred within ≤ 28 days before enrollment.
c. Acute myocardial infarction occurred within ≤ 6 months before enrollment.
d. Have any history of heart failure that has reached New York Heart Association Grade III / IV within ≤ 6 months before enrollment, or left ventricular ejection fraction <50%.
e. Ventricular arrhythmia of grade ≥ 2 occurred within ≤ 6 months before enrollment.
f. Cerebrovascular accident (CVA) occurred within ≤ 6 months before enrollment
g. Those with high blood pressure who cannot be controlled well with antihypertensive medications. The symptoms are: systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg (within 3 months).
h. Significant cardiac conduction abnormalities, including a history of QTc interval prolongation syndrome (QTc interval prolongation> 450 ms) and/or a history of pacemaker implantation.
14) Patients receiving oral or parenteral anticoagulant or thrombolytic treatment for therapeutic purposes during screening and/or during the study should be excluded.
15) The patient has brain metastases or meningeal metastases.
16) People who are allergic to any research medication.
17) Have had an allogeneic stem cell transplant or organ transplant.
18) Corticosteroids (prednisone or similar drugs at doses greater than 10 mg/day are required for ≤ 14 days before enrollment)
Equal dose) or other immunosuppressive agents for systemic treatment.
Note: Patients who are currently or previously using any of the following steroid regimens can be selected:
a. Adrenaline replacement steroids (prednisone ≤10mg / d or equivalent dose of similar drugs)
b. Local, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids with minimal systemic absorption.
c. Short-term (≤ 7 days) use of corticosteroids for prophylaxis (for example, to prevent contrast agent hypersensitivity or antiemetic for specific chemotherapy) or for the treatment of non-autoimmune conditions (such as delayed hypersensitivity caused by contact allergens).
19) Live vaccinations were given within 4 weeks before randomization (Note: seasonal influenza vaccines are usually inactivated vaccines and are allowed. Vaccines used in the nasal cavity are live vaccines and are not allowed).
20) Have received immunotherapy (such as interleukin, interferon, thymosin, etc.) or any experimental treatment within 28 days or 5 half-lives (whichever is shorter, but at least 14 days) before enrollment.
21) Having received anti-PD-1, anti-PD-L1, anti-PD-L2, or any other specific antibody or drug therapy that targets T-cell co-stimulation or checkpoint pathways.
22) For those with a history of uncontrolled epilepsy, central nervous system disease, or mental disorder, it is up to the investigator to determine whether their clinical severity prevents the signing of informed consent or affects the patient's compliance with oral medication.
23) There are potential medical conditions or alcohol/drug abuse or dependence that the investigator believes are not conducive to the administration of the study drug or affect the interpretation of drug toxicity or adverse events.

研究实施时间：

Study execute time：

从 From 2020-10-08 00:00:00至 To 2023-10-08 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2020-10-08 00:00:00 至 To 2022-10-08 00:00:00  

干预措施：

Interventions：

组别：

胃腺癌组

样本量：

60

Group：

stomach adenocarcinoma group

Sample size：

干预措施：

PD-1单抗联合阿帕替尼

干预措施代码：

Intervention：

PD-1 inhibitor and apatinib

Intervention code：

组别：

食管鳞癌组

样本量：

60

Group：

esophageal squamous cell carcinoma group

Sample size：

干预措施：

PD-1单抗联合安罗替尼

干预措施代码：

Intervention：

PD-1 inhibitor and anlotinib

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)：

复旦大学附属中山医院 

单位级别：

三级甲等 

Institution
hospital：

Zhongshan Hospital, Fudan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

有效率

指标类型：

主要指标

Outcome：

overall 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：

TCR免疫组库信息

指标类型：

主要指标

Outcome：

T cell receptor repertoire sequencing information

Type：

Primary 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：

外周血

组织：

Sample Name：

Peripheral 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）：

观察性研究，无需随机

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

This is an observational study, so no randomization.

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）：

以研究结果成文，并公开发表为准。

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

The results of this study is published as an article.

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：

采用病例记录表进行数据采集和管理

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

Case Record Form will be used.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-08-10 22:21:48