ChiCTR2500095781 版本V1.0 版本创建时间2025/01/13 15:37:14 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：

ChiCTR2500095781 

最近更新日期：

Date of Last Refreshed on：

2025-01-13 15:36:58 

注册时间：

Date of Registration：

2025-01-13 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

化疗联合信迪利单抗序贯伏美替尼一线治疗具有EGFR敏感突变的晚期NSCLC的探索性临床研究

Public title：

An exploratory clinical study of chemotherapy combined with sintilimab followed by vormetinib as first-line treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations

注册题目简写：

English Acronym：

研究课题的正式科学名称：

化疗联合信迪利单抗序贯伏美替尼一线治疗具有EGFR敏感突变的晚期NSCLC的探索性临床研究

Scientific title：

An exploratory clinical study of chemotherapy combined with sintilimab followed by vormetinib as first-line treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations

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：

马进安 

研究负责人：

马进安 

Applicant：

Jinan Ma 

Study leader：

Jinan Ma 

申请注册联系人电话：

Applicant telephone：

+86 13973192715

研究负责人电话：

Study leader's telephone：

+86 13973192715

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：

3420248369@qq.com

研究负责人电子邮件：

Study leader's E-mail：

4320248369@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：

中南大学湘雅二医院

研究负责人通讯地址：

湖南省长沙市芙蓉区人民中路139号

Applicant address：

The Second Xiangya Hospital of Central South University

Study leader's address：

No 139 Renmin Road Furong district

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：

中南大学湘雅二医院

Applicant's institution：

The Second Xiangya Hospital of Central South University

研究负责人所在单位：

中南大学湘雅二医院

Affiliation of the Leader：

Second Xiangya Hospital of CSU

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：

LYEC2024-0381

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：

中南大学湘雅二医院临床研究伦理委员会

Name of the ethic committee：

Clinical Research Ethics Committee of the Second Xiangya Hospital, Central South University

伦理委员会批准日期：

Date of approved by ethic committee：

2024-10-30 00:00:00

伦理委员会联系人：

蒋屏

Contact Name of the ethic committee：

Ping Jiang

伦理委员会联系地址：

湖南省长沙市芙蓉区人民中路139号

Contact Address of the ethic committee：

No 139 Renmin Road Furong district

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 731 85292476

伦理委员会联系人邮箱：

Contact email of the ethic committee：

xy2gcpjiang@163.com

研究实施负责（组长）单位：

中南大学湘雅二医院

Primary sponsor：

Second Xiangya Hospital of CSU

研究实施负责（组长）单位地址：

湖南省长沙市芙蓉区人民中路139号

Primary sponsor's address：

No 139 Renmin Road Furong district

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖南

市(区县)：

Country：

China

Province：

Hunan

City：

单位(医院)：

中南大学湘雅二医院

具体地址：

湖南省长沙市芙蓉区人民中路139号

Institution
hospital：

Second Xiangya Hospital of CSU

Address：

No 139 Renmin Road Furong district

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Self support

Target disease：

Histologically or cytologically confirmed as locally advanced or metastatic NSCLC (including patients with recurrence after prior surgical treatment or initial diagnosis of IIIB/C and IV stages according to the AJCC 9th edition lung cancer staging criteria). Confirmed as locally advanced or metastatic NSCLC without prior systemic therapy. Patients who have received local treatment may participate

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 II期临床试验 

Study phase：

2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

以历史临床试验为对照，观察在未接受过任何系统治疗的EGFR敏感突变的局部晚期或转移性NSCLC患者中，“化疗联合PD-1单抗序贯EGFR-TKIs”给药模式用于一线治疗的生存获益及安全性。  

Objectives of Study：

The aim of this study was to compare the survival benefit and safety of "chemotherapy plus PD-1 monoclonal antibody followed by EGFR-Tkis" regimen as first-line treatment for locally advanced or metastatic NSCLC patients with EGFR sensitive mutations who had not received any systemic treatment.

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.年龄在18-75岁之间；
2.组织学或细胞学确诊为局部晚期或转移性NSCLC（包括既往手术治疗后复发的或初诊的IIIB/C和IV期患者。按AJCC第9版肺癌分期标准）；
3.确诊为局部晚期或转移性NSCLC之后未接受过任何系统性治疗。对于接受过局部治疗的患者，如果局部治疗范围内的病灶为非靶病灶，患者可以参加研究。
4.诊断为局部晚期或转移性NSCLC的肿瘤组织样本或血液样本经实验室检测确认为EGFR敏感突变（包括外显子19缺失或外显子21 L858R突变，两者单独存在或共存EGFR其他位点突变均可）。如果肿瘤组织可及，推荐送检肿瘤组织；若肿瘤组织不可及或患者不可接受组织活检，则送检血液样本。
5.ECOG PS评分为0或1并且在之前2周没有恶化，最小预期生存≥12周。
6.患者至少有1个肿瘤病灶既往未经过放疗等局部治疗，也没有在筛选期接受过组织活检，并且在基线时可以准确测量，基线期最长径≥10 mm（如果是淋巴结，要求短径≥15 mm）。选择的测量方法适合准确重复测量，可以是计算机断层扫描（CT）或磁共振扫描（MRI）。如仅存在一个可测量的病灶且既往未经过照射等局部治疗，则可接受其作为靶病灶，在诊断性活检至少14天之后进行肿瘤病灶基线评价。
7.重要器官的功能符合下列要求（注：筛检前14天内不允许使用任何血液成分及造血生长因子如升白药、升血小板药、纠正贫血药）： A. 中性粒细胞绝对计数（ANC）≥1.5×109/L; B. 血小板计数≥100×109/L； C. 血红蛋白≥9 g/dL； D. 血清白蛋白≥2.8g/dL； E. 胆红素≤1.5×正常值上限（ULN）； F. 丙氨酸转氨酶（ALT）≤2.5×ULN，天冬氨酸转氨酶（AST）≤2.5×ULN；伴有肝转移的受试者，则ALT和AST≤5×ULN； G. 肌酐＞1.5×ULN并且肌酐清除率＜50 mL/min（通过Cockcroft-Gault公式计算）；仅当肌酐＞1.5×ULN时才需要确认肌酐清除率； H. 活化部分凝血活酶时间（APTT）≤1.5×ULN，国际标准化比值（INR）≤1.5（对于使用稳定剂量的预防性抗凝治疗时，参考具体药物的监测要求可接受超出本范围）； I. 心脏功能检测：基线心电图显示无PR间期延长或房室传导阻滞。
8.女性受试者必须已采取可靠的避孕措施，应在第一次服用研究药物前7天内尿或血清妊娠呈阴性；有生育潜力者和伴侣为育龄期女性的男性受试者，需要在研究治疗期间、以及在最后一次给药后8周内采用一种经医学认可的避孕措施（如避孕药或避孕套）。
9.全身使用的皮质激素（强的松> 10 mg/d或等效剂量）在入组前停用至少2周。
10.受试者自愿加入本研究，并签署知情同意书，依从性好，配合随访。

Inclusion criteria

1.Age between 18-75 years. 2.Histologically or cytologically confirmed as locally advanced or metastatic NSCLC (including patients with prior surgical treatment who have recurred or were initially diagnosed as IIIB/C and IV stages according to the AJCC 9th edition lung cancer staging criteria). 3.Have not received any systemic treatment after the diagnosis of locally advanced or metastatic NSCLC. For patients who have received local treatment, if the target lesion is not within the scope of local treatment, the patient may participate in the study. 4.The tissue sample or blood sample of the tumor confirmed by laboratory tests as EGFR sensitive mutations (including exon 19 deletion or exon 21 L858R mutation, which can exist alone or together with other mutations in the EGFR gene). If the tumor tissue is available, it is recommended to submit the tumor tissue; if the tumor tissue is not available or the patient cannot tolerate biopsy, the blood sample should be submitted. 5.ECOG PS score of 0 or 1 and no deterioration within the past 2 weeks, with a minimum expected survival of at least 12 weeks. 6.The patient has at least one tumor lesion that has not been previously treated with radiation or other local therapies, and has not been screened within the past 2 weeks, and the longest diameter is >=10 mm (if it is a lymph node, the shortest diameter is >=15 mm). The measurement method selected is suitable for accurate repeated measurement, which can be computed tomography (CT) or magnetic resonance imaging (MRI). If only one measurable lesion exists and has not been previously treated with radiation or other local therapies, it may be accepted as a target lesion and evaluated for baseline status at least 14 days after diagnostic biopsy. 7.Vital organ function meets the following requirements (Note: no blood components and hematopoietic growth factors such as leukopenia, thrombocytopenia, and anemia correction drugs are allowed within 14 days before screening) : A. Absolute neutrophil count (ANC) >=1.5×10^9/L; B. Platelet count >=100×10^9/L; C. hemoglobin >=9 g/dL; D. serum albumin >=2.8g/dL; E. Bilirubin <=1.5× upper limit of normal value (ULN); F. alanine aminotransferase (ALT) <=2.5×ULN, aspartate aminotransferase (AST) <=2.5×ULN; For patients with liver metastasis, ALT and AST<=5×ULN; G. Creatinine > 1.5×ULN and creatinine clearance < 50 mL/min (calculated by the Cockcroft-Gault formula); Creatinine clearance should be confirmed only if creatinine > 1.5×ULN. H. Activated partial thromboplastin time (APTT) <=1.5×ULN and international normalized ratio (INR) <=1.5 (beyond this range may be acceptable according to drug-specific monitoring requirements when using a stable dose of prophylactic anticoagulation); I. Cardiac function testing: baseline electrocardiogram showed no PR interval prolongation or atrioventricular block. 8.Female participants must be using reliable contraception and should have a urine or serum negative for pregnancy within 7 days before the first dose of study drug; Childbearing potential and male participants whose partner was a woman of childbearing age were required to use a medically approved contraceptive method (such as the contraceptive pill or condom) during the study treatment and for up to 8 weeks after the last dose. 9.Systemic corticosteroids (prednisone > 10 mg per day or equivalent) were discontinued for at least 2 weeks before enrollment. 10.The subjects voluntarily participated in the study, signed the informed consent form, and the compliance was good.

排除标准：

1.伴随以下任何疾病状态： A． 肿瘤组织学或细胞学病理证实合并小细胞肺癌成分或肉瘤样病变； B． 已知有脑膜转移的患者； C． 脊髓压迫或脑转移，除非无症状，病情稳定，且在首次治疗前至少2周不需要类固醇治疗； D． 未控制的胸腔积液、心包积液，或需要反复引流的腹水（一月一次或更频繁）；经过引流后症状稳定至少两周的受试者可入组。
2.接受过下列任一治疗： A．曾经使用过任何EGFR-TKIs治疗； B. 首次治疗前4周内，患者曾接受重大手术或有严重外伤； C. 首次治疗前4周内，接受过超过30%的骨髓照射，或者接受过大面积放疗； D. 研究药物首次给药前7天内，使用过CYP3A4强抑制剂、诱导剂或为CYP3A4敏感底物的治疗窗窄的药物; E. 首次治疗前2周内，患者使用免疫抑制药物治疗其他疾病； F. 既往接受过任何不适合根治性手术或放疗的晚期NSCLC全身抗肿瘤治疗，包括化疗、生物疗法、免疫疗法或任何研究药物； G. 有任何并发症或其他恶性肿瘤且在首次治疗后2年内需要治疗或大手术的患者。
3.在开始研究治疗时，有大于CTCAE 1级的未能缓解的既往治疗（如辅助化疗）遗留毒性；脱发和既往化疗引起的2级神经毒性者除外。
4.首次使用研究药物前5年内曾诊断为任何其他恶性肿瘤，除外具有低风险转移和死亡风险的恶性肿瘤（5年生存率＞90%），如经充分治疗的基底细胞或鳞状细胞皮肤癌或宫颈原位癌除外。
5.难治性恶心、呕吐或慢性胃肠道疾病，不能吞咽药物或曾接受大范围的肠切除术，可能影响口服药物的摄入、转运或吸收。
6.确诊或可疑的间质性肺病或特发性肺纤维化病史、药物性肺炎、特发性肺炎、或其他严重影响肺功能的中重度肺部疾病（除外≤1级放射性肺炎）。
7.有活动性的自身免疫性疾病、自身免疫性疾病史（如间质性肺炎、结肠炎、肝炎、垂体炎、血管炎、肾炎、甲状腺功能亢进症、甲状腺功能减退症，包括但不限于这些疾病或综合症）；除外：a. 白癜风或已痊愈的童年时代哮喘/过敏，成人后无需任何干预的受试者；b. 使用稳定剂量的甲状腺替代激素治疗的自身免疫介导甲状腺功能减退症的受试者；c. 使用稳定剂量的胰岛素治疗I型糖尿病的受试者。
8.有免疫缺陷病史，包括HIV检测阳性，或患有其他获得性、先天性免疫缺陷疾病，或有器官移植史和异基因骨髓移植史，或自体造血干细胞移植史。
9.通过病史或CT检查发现有活动性肺结核感染，或入组前1年内有活动性肺结核感染病史的受试者，或超过1年以前有活动性肺结核感染病史但未经正规治疗的受试者。
10.存在活动性乙型肝炎（乙肝病毒表面抗原（HBsAg）阳性，且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）。
11.妊娠期或哺乳期妇女。
12.已知对任何研究治疗及其辅料过敏或发生过超敏反应。
13.未得到控制的并发疾病，包括但不限于：症状性充血性心力衰竭、左心室射血分数（LVEF）＜50%、未得到控制的高血压、不稳定型心绞痛、未得到控制的心律失常、重大癫痫发作、上腔静脉综合征，或可能影响研究依从性、导致不良事件风险显著增加或影响受试者提供书面知情同意能力的精神疾病/社会状况。
14.经研究者判断，受试者有其他可能导致其被迫中途终止研究的因素，如患有其他严重疾病（含精神疾病）需要合并治疗，实验室检查值严重异常，和/或可能影响受试者安全或试验资料收集的家庭或社会因素。

Exclusion criteria：

1.Accompanied by any of the following disease conditions: A. Small cell lung cancer components or sarcomatoid lesions were confirmed by tumor histology or cytology. B. Patients with known leptomeningeal metastases; C. Spinal cord compression or brain metastases, unless asymptomatic, in stable condition, and not requiring steroids for at least 2 weeks prior to the first treatment; D. Uncontrolled pleural effusion, pericardial effusion, or ascites that requires repeated drainage (once a month or more); Subjects with stable symptoms for at least two weeks after drainage were eligible for enrollment. 2.Received any of the following treatments: A. Having received any EGFR-TKIs treatment; B. Major surgery or severe trauma within 4 weeks before the first treatment; C. Irradiation of more than 30% of bone marrow or large area of radiation within 4 weeks before the first dose of treatment; D. Use of a CYP3A4 strong inhibitor, inducer, or drug with a narrow therapeutic window as a CYP3A4 sensitive substrate within 7 days before the first dose of the study drug; E. Use of immunosuppressive drugs for other diseases within 2 weeks before the first treatment; F. Patients with advanced NSCLC who have received any previous systemic anti-tumor therapy, including chemotherapy, biological therapy, immunotherapy, or any investigational drug, which is not suitable for radical surgery or radiotherapy; G. Patients with any complications or other malignancies requiring treatment or major surgery within 2 years of initial treatment. 3.Residual toxicity from previous therapy (e.g., adjuvant chemotherapy) that was not responsive to CTCAE grade 1 or greater at the time of initiation of study treatment; Patients with alopecia and grade 2 neurotoxicity from previous chemotherapy were excluded. 4.Any other malignancy diagnosed within 5 years before the first use of study drug, except those with a low risk of metastasis and death (5-year survival rate > 90%), with the exception of adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ. 5.Refractory nausea, vomiting, chronic gastrointestinal diseases, inability to swallow drugs, or a history of major bowel resection may affect oral drug intake, transport, or absorption. 6.Confirmed or suspected history of interstitial lung disease or idiopathic pulmonary fibrosis, drug-induced pneumonia, idiopathic pneumonia, or other moderate-to-severe pulmonary diseases that severely affect lung function (except grade ≤1 radiation pneumonitis). 7.Active autoimmune disease, history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Exceptions: a. subjects with vitiligo or cured childhood asthma/allergy without any intervention in adulthood; b. subjects with autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; c. Subjects treated with stable doses of insulin for type I diabetes. 8.A history of immunodeficiency, including testing positive for HIV or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation or autologous hematopoietic stem-cell transplantation. 9.Subjects with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before but without regular treatment. 10.Presence of active hepatitis B (positive hepatitis B virus surface antigen (HBsAg) and HBV DNA>=500 IU/mL) and hepatitis C (positive hepatitis C antibody and HCV-RNA above the detection limit of the analytical method). 11.Pregnant or lactating women. 12.Known allergies or hypersensitivity reactions to any study treatment and its excipients. 13.Uncontrolled concurrent diseases, including but not limited to: Symptomatic congestive heart failure, left ventricular ejection fraction (LVEF) < 50%, uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmia, major seizures, superior vena cava syndrome, Or mental illness/social conditions that may affect study compliance, result in a significantly increased risk of adverse events, or affect the ability of the subject to provide written informed consent. 14.In the judgment of the investigator, the subject has other factors that may lead to the forced termination of the study, such as other serious medical conditions (including mental disorders) requiring combined treatment, severely abnormal laboratory results, and/or family or social factors that may affect the subject's safety or the trial data collection.

研究实施时间：

Study execute time：

从 From 2024-09-01 00:00:00至 To 2027-09-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-11-25 00:00:00 至 To 2025-09-01 00:00:00  

干预措施：

Interventions：

组别：

治疗组

样本量：

5

Group：

Treatment group

Sample size：

干预措施：

化疗联合靶向及免疫治疗

干预措施代码：

Intervention：

Chemotherapy combined with targeted therapy and immunotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖南 

市(区县)：

  

Country：

China 

Province：

Hunan 

City：

 

单位(医院)：

中南大学湘雅二医院 

单位级别：

三级甲等 

Institution
hospital：

Second Xiangya Hospital of CSU

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：

Progression-free survival

Type：

Primary indicator

测量时间点：

每8周一次

测量方法：

irRECIST标准影像学评估，包括但不限于MRI、PETCT、CT

Measure time point of outcome：

Once every 8 weeks

Measure method：

Imaging evaluation, including but not limited to MRI, PETCT, and CT(irRECIST criteria)

指标中文名：

治疗期间发生的任何不良事件

指标类型：

次要指标

Outcome：

Any adverse events that occurred during treatment

Type：

Secondary indicator

测量时间点：

治疗全过程

测量方法：

实验室检测与患者主观感觉及临床医生评估

Measure time point of outcome：

whole course of treatment

Measure method：

Laboratory tests and patient subjective feeling and clinician evaluation

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：

出组时

测量方法：

irRECIST标准影像学评估，包括但不限于MRI、PETCT、CT

Measure time point of outcome：

time of out of group

Measure method：

Imaging evaluation, including but not limited to MRI, PETCT, and CT(irRECIST criteria)

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：

出组时

测量方法：

irRECIST标准影像学评估，包括但不限于MRI、PETCT、CT

Measure time point of outcome：

time of out of group

Measure method：

Imaging evaluation, including but not limited to MRI, PETCT, and CT(irRECIST criteria)

指标中文名：

缓解深度

指标类型：

次要指标

Outcome：

DepOR

Type：

Secondary indicator

测量时间点：

每8周一次

测量方法：

irRECIST标准影像学评估，包括但不限于MRI、PETCT、CT

Measure time point of outcome：

Once every 8 weeks

Measure method：

Imaging evaluation, including but not limited to MRI, PETCT, and CT(irRECIST criteria)

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：

病人死亡

测量方法：

随访

Measure time point of outcome：

Death of a patient

Measure method：

Follow-up

指标中文名：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of relief, DoR

Type：

Secondary indicator

测量时间点：

病人死亡

测量方法：

随访

Measure time point of outcome：

Death of a patient

Measure method：

Follow-up

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

Sample Name：

NA

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

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:

不公开/Private

盲法：

无

Blinding：

None

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）：

研究公开发表后邮件联系研究负责人获取。

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

After the research is publicly published, contact the research leader by email to obtain it.

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：

每个签署知情同意书的患者需要完成eCRF。 数据直接输入到eCRF中。 所有的修正都应该被记录，包括旧信息、新信息、修正的人员、修正日期以及变更原因。此外，还应包括重大修正的原因。 主要研究者必须审查eCRF的完整性和准确性，并且必须署名和注明日期。此外，研究者必须对所有输入到eCRF的数据的准确性和真实性负全部责任。 在研究监查员定期访问期间，将审查eCRF的完整性和准确性。 数据处理程序的全部细节将记录在单独的数据管理计划中。

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

Each patient who signed an informed consent form was required to complete the eCRF. Data were entered directly into the eCRF. All corrections should be documented, including old information, new information, who made the correction, the date of the correction, and the reason for the change. In addition, reasons for major amendments should be included. The eCRF must be reviewed for completeness and accuracy by the principal investigator and must be signed and dated. In addition, the investigator must take full responsibility for the accuracy and authenticity of all data entered into the eCRF. eCRF will be reviewed for completeness and accuracy during regular visits by study monitors. Full details of the data handling procedures will be documented in a separate data management plan.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2025-01-13 15:36:58