ChiCTR2400089355 版本V1.0 版本创建时间2024/09/06 10:49:06 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：

ChiCTR2400089355 

最近更新日期：

Date of Last Refreshed on：

2024-09-06 10:48:07 

注册时间：

Date of Registration：

2024-09-06 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

ctDNA甲基化检测对中晚期 NSCLC 治疗疗效监测作用的研究

Public title：

Study on the role of ctDNA methylation detection in monitoring the therapeutic efficacy of advanced NSCLC treatment.

注册题目简写：

YTHJJJHJ-2024

English Acronym：

YTHJJJHJ-2024

研究课题的正式科学名称：

ctDNA甲基化检测对中晚期 NSCLC 治疗疗效监测作用的研究

Scientific title：

Study on the role of ctDNA methylation detection in monitoring the therapeutic efficacy of advanced NSCLC 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：

黄李华; 孟淑燕 

研究负责人：

周崧雯 

Applicant：

Lihua Huang; Shuyan Meng 

Study leader：

wendy 

申请注册联系人电话：

Applicant telephone：

+86 136 3635 9093

研究负责人电话：

Study leader's telephone：

+86 138 1686 0220

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：

shark91298@163.com

研究负责人电子邮件：

Study leader's E-mail：

songwenzhou2017@vip.126.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：

上海市杨浦区507号肿瘤科

研究负责人通讯地址：

上海市杨浦区政民路507号

Applicant address：

No. 507, Oncology Department, Yangpu District, Shanghai,China

Study leader's address：

No. 507 Zhengmin Road, Yangpu District, Shanghai

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：

上海市肺科医院

Applicant's institution：

Shanghai Pulmonary Hospital.

研究负责人所在单位：

上海市肺科医院

Affiliation of the Leader：

Shanghai Pulmonary 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：

L24-409-1

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：

上海市肺科医院医学伦理委员会

Name of the ethic committee：

Instituional Review Board Shanghai Pulmonary Hospital Tongji University

伦理委员会批准日期：

Date of approved by ethic committee：

2024-08-21 00:00:00

伦理委员会联系人：

桂涛

Contact Name of the ethic committee：

Gui Tao

伦理委员会联系地址：

上海市杨浦区政民路507号

Contact Address of the ethic committee：

No. 507 Zhengmin Road, Yangpu District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 21 65115006

伦理委员会联系人邮箱：

Contact email of the ethic committee：

fkyygcp@163.com

研究实施负责（组长）单位：

上海市肺科医院

Primary sponsor：

Shanghai Pulmonary Hospital

研究实施负责（组长）单位地址：

上海市杨浦区政民路507号

Primary sponsor's address：

No. 507 Zhengmin Road, Yangpu District, Shanghai

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)：

上海市肺科医院

具体地址：

上海市杨浦区政民路507号

Institution
hospital：

Shanghai Pulmonary Hospital

Address：

No. 507 Zhengmin Road, Yangpu District, Shanghai

经费或物资来源：

ctDNA 甲基化检测对中晚期 NSCLC 治疗疗效监测作用的研究

Source(s) of funding：

Sponsored by Shanghai He Shuo Hong Jing Biomedical company

Target disease：

advanced non-small cell lung cancer

Target disease code：

研究类型：

诊断试验

Study type：

Diagnostic test

研究所处阶段：

 探索性研究/预试验 

Study phase：

0

研究设计：

诊断试验诊断准确性 

Study design：

Diagnostic test for accuracy 

研究目的：

1. 主要目的 （1）鉴定及筛选具有肺癌特征的甲基化生物标志物，建立并优化适合液体活检的ctDNA定量PCR甲基化检测体系。 （2）验证ctDNA甲基化检测体系较血癌标能更早发现肺癌化疗、免疫治疗或靶向治疗耐药。 （3）构建以ctDNA甲基化拷贝数(mhGE/ML)为评估单位的中晚期NSCLC治疗疗效评估及动态监测体系。 2. 次要目的 对比ctDNA甲基化检测体系与血癌标监测肺癌治疗疗效的准确性和可靠性，评价两种方法检测结果一致性（评价指标包括阳性符合率、阴性符合率等）。  

Objectives of Study：

Main Objectives (1) To identify and screen for methylation biomarkers characteristic of lung cancer and to establish and optimize a ctDNA quantitative PCR methylation detection system suitable for liquid biopsies. (2) To validate that the ctDNA methylation detection system can detect resistance to chemotherapy, immunotherapy, or targeted therapy for lung cancer earlier than blood cancer biomarkers. (3) To construct a system for evaluating the therapeutic efficacy and dynamic monitoring of advanced NSCLC, using ctDNA methylation copy number (mhGE/ML) as the assessment unit. Secondary Objectives To compare the accuracy and reliability of the ctDNA methylation detection system with blood cancer biomarkers in monitoring the therapeutic efficacy of lung cancer, and to evaluate the consistency of the test results between the two methods (evaluation indicators include positive agreement rate, negative agreement rate, etc.).

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）获得病理诊断的、有影像学依据的中晚期NSCLC（IIIB-IV期）； （2）年龄小于70岁，大于18岁； （3）KPS评分大于80分； （4）接受一线或者二线免疫治疗联合化疗的肺癌患者（驱动基因野生型）； （5）接受靶向治疗的肺癌患者（驱动基因阳性）。

Inclusion criteria

1. Patients with pathologically diagnosed, image-based advanced NSCLC (Stage IIIB-IV);
2.(2) Age less than 70 years and older than 18 years;
3.(3) KPS score greater than 80;
4.(4) Lung cancer patients receiving first-line or second-line immunotherapy combined with chemotherapy (wild-type driver gene);
5.(5) Lung cancer patients receiving targeted therapy (positive driver gene).

排除标准：

1.年龄大于70岁、小于18岁、KPS评分小于80分、无明确病理诊断患者、同时患有其他肿瘤患者。

Exclusion criteria：

1.Patients older than 70 years, younger than 18 years, with a KPS score less than 80, without a definitive pathological diagnosis, and patients with concurrent other tumors.

研究实施时间：

Study execute time：

从 From 2024-09-15 00:00:00至 To 2027-09-15 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-09-15 00:00:00 至 To 2025-09-15 00:00:00  

诊断试验：

Diagnostic Tests：

金标准或参考标准（即可准确诊断某疾病的单项方法或多项联合方法，在本研究中用于诊断是否有该病的临床参考标准）：

病理诊断是诊断肺癌的金标准 目前CT测量病灶大小变化是临床评估肺癌治疗疗效的参考标准

Gold Standard or Reference Standard (The clinical reference standards required to establish the presence or absence of the target condition in the tested population in present study):

Pathological diagnosis is the gold standard for diagnosing lung cancer. Currently, CT measurement of lesion size change is the reference standard for clinical assessment of the efficacy of lung cancer treatment.

指标试验（即本研究的待评估诊断试验，无论为方法、生物标志物或设备，均请列出名称）：

ctDNA液态活检特定基因甲基化定量PCR检测，中晚期非小细胞肺癌治疗前后及耐药时外周血检测特定基因甲基化定量PCR的变化

Index test:

ctDNA liquid biopsy for specific gene methylation quantitative PCR detection. Changes in peripheral blood detection of specific gene methylation quantitative PCR before and after treatment and at the time of drug resistance in advanced and middle-stage non-small cell lung cancer.

目标人群（可以是某种疾病患者或正常人群，详细描述其疾病特征，注意应纳入符合分布特点的全序列病例，具有良好的代表性）

中晚期非小细胞肺癌100例、 获得病理诊断的、年龄18-70岁、KPS评分大于80得分；健康人群30例

例数:

Sample size:

130

Target condition (The target condition is a particular disease or disease stage that the index test will be intended to identify. Please specify the characteristics in detail; the population should has a complete spectrum and good representative):

One hundred cases of advanced and middle-stage non-small cell lung cancer, with a pathological diagnosis, aged between 18 and 70 years, and a KPS score greater than 80 points. 30 cases of healthy population。

容易混淆的疾病人群（即与目标疾病不易区分的一种或多种不同疾病，应避免采用正常人群对照的病例-对照设计）：

无

例数:

Sample size:

0

Population with condition difficult to distinguish from the target condition, the normal population in a case-control study design should be avoid:

None

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)：

上海市肺科医院 

单位级别：

三级甲等 

Institution
hospital：

Shanghai Pulmonary Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

外周血特定基因甲基化定量PCR检测

指标类型：

主要指标

Outcome：

Peripheral blood specific gene methylation quantitative PCR detection.

Type：

Primary indicator

测量时间点：

治疗前后、耐药时

测量方法：

采集患者清晨空腹外周血临床样本，每例患者每次收集外周血3管，进行特定基因定量甲基化检测

Measure time point of outcome：

before and after therapy 、drug resistance

Measure method：

Clinical samples of peripheral blood were collected from patients in the early morning after an overnight fast, with three tubes of peripheral blood collected from each patient per visit for specific gene quantitative methylation detection.

指标中文名：

准确度

指标类型：

主要指标

Outcome：

Accuracy

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

灵敏度

指标类型：

主要指标

Outcome：

Sensitivity

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

特异度

指标类型：

主要指标

Outcome：

Specificity

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

阳性预测值

指标类型：

次要指标

Outcome：

Positive predicative value

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

阴性预测值

指标类型：

次要指标

Outcome：

Negative predictive value

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：

外周血

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 70 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

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）：

不共享

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

non

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：

1、CRF表格由资助公司指派的CRO填写、或者研究团队成员填写 2、临床数据管理员参与数据收集方案的早期讨论，然后监督基于临床试验方案的数据收集工具的开发。受试者入组开始，数据管理员需要确保数据的收集、验证、完整性和一致性。临床数据管理员与其他数据提供者（如处理所收集的血液样本的实验室）进行联络，并确保这些数据安全传输，并与临床试验中收集的其他数据保持一致。在临床试验结束时，临床数据管理员确保所有预期采集的数据都已被记录在案，并且所有数据管理活动都已完成。在这一阶段，数据被宣布为最终数据(数据库锁定 ), 临床数据管理员将数据交予统计分析。 2、开展数据管理活动时应遵循SOP程序，并支持在开展数据管理活动时遵守适用法律和准则(如ICH GCP 和21CFR Part 11)的义务。 3、需遵循标准操作程序、使用的临床数据管理系统(CDMS)、数据来源说明、数据处理流程、数据传输格式和流程以及要质量控制程序 4、病例报告表（CRF）是临床试验的数据收集工具，可以是纸质的，也可以是电子的。纸质CRF将被打印出来，通常使用无碳纸张，并被寄往进行临床试验的研究机构，完成临床试验后再将其寄回至数据管理部门。电子CRF使数据能够使用计算机直接输入到字段中，并能通过电子方式传送至数据管理部门。CRF的设计需要考虑到： 临床试验方案要求收集的信息，并计划将这些信息用于统计分析。在可能的情况下，标准的CRF可重复使用来收集大多数临床试验中通用的数据，如受试者的人口学信息。除CRF设计外，电子试验设计还包括逻辑核查编程。逻辑核查用于在以下情况下提出质疑信息：当输入不一致的数据，将某些数据点从一页CRF映射到另一页CRF中，计算某些诸如受试者的年龄、BMI等字段。逻辑核查有助于研究者正确地输入正确的数据，也有助于提高临床试验数据的质量。 5、如果使用电子CRF的临床试验，数据库设计和CRF设计是密切相关的。电子CRF可以将数据输入基础关系数据库。对于使用纸质CRF的临床试验，关系型数据库是单独建立的。在这两种情况下，关系数据库都可以使所有数据都收集在CRF中。计算机数据验证：所有用于临床试验处理和管理的计算机系统都必须经过严格验证，以确保运行无误并且结果可重复。 6、当使用电子CRF时，数据录入在临床研究中心由已经获得相应权限的人员进行。在使用纸质CRF时，页面由数据录入员录入。最佳的做法是先进行一轮数据录入，在完成数据输入后在进行第二轮录入或者由独立的操作者进行验证。第一轮和第二轮之间的任何差异都可以得到解决，从而使输入的数据是一个完整的数据，能够真实地反映了CRF上的记录。如果操作人员无法识别某个数据，则应通知数据管理员，以便向填写该数据的人澄清。 7、中心实验室数据：在临床试验过程中收集的样本可能会被送到一个中心实验室进行分析。临床数据管理员与中央实验室联系，并在数据传输协议中商定数据格式和传输时间表。采集样本的日期和时间可与CRF进行核对，以确保所有采集的样本都已被分析。 8、其他外部数据：临床试验数据的分析可由实验室、图像处理专家或其他第三方进行。临床数据管理员与这些数据提供者联系，并商定数据格式和传输时间表。数据可与CRF进行核对，以确保一致性。 9、不良事件稽查：CRF收集临床试验过程中报告的不良事件，但有一个单独的程序，以确保严重的不良事件能迅速报告。临床数据管理员必须确保这些程序之间的数据一致。 10、患者记录数据：如果要求受试者记录数据(如每日症状)，则提供日记本供其填写。这类数据的数据管理需要采用与CRF数据不同的方法，例如，提出数据质疑一般是不切实际的。病人日记可采用纸质或电子(电子日记)形式。这种电子日记一般采取手持设备的形式，使当事人能够输入所需数据，并将这些数据传送到中央服务器。 11、追踪报表：临床数据管理员生成和使用的典型报表包括：CRF完成状态/缺失页面；数据质疑状态；数据质疑未在指定时间范围内解决；常见的数据质疑（用来帮助识别可进行改善的地方）。 12、质量控制：质量控制适用于临床数据管理过程中的各个阶段，通常由SOP规定。 13、数据保密及研究结果归属： 匿名化处理：在研究者或者资助方临床协调员处理数据时，应尽可能采用匿名化或去标识化手段，确保受试者的个人信息不会在研究报告或公开的数据中被识别。 数据安全：研究机构需要采取适当的技术和组织措施来保护存储和传输中的受试者数据，防止未授权的访问、泄露、丢失或破坏。 信息访问限制：只有直接参与研究的团队成员以及资助方CRC才能访问受试者的个人信息，并且他们必须承诺保密。 保密协议：研究人员和所有可能接触到受试者信息的团队成员以及资助方应签署保密协议，承诺不泄露任何个人信息。 研究者与资助方双方约定，所有因进行本研究或履行研究合同而产生或开发的项目成果及知识产权均归属于上海市肺科医院所有。

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

The CRF forms are filled out by a CRO assigned by the funding company or by the research team members. The clinical data manager participates in early discussions of the data collection plan and then supervises the development of data collection tools based on the clinical trial protocol. Starting from the enrollment of subjects, the data manager needs to ensure the collection, verification, integrity, and consistency of the data. The clinical data manager liaises with other data providers (such as laboratories processing the collected blood samples) and ensures that these data are securely transmitted and consistent with other data collected in the clinical trial. At the end of the clinical trial, the clinical data manager ensures that all expected data have been documented and that all data management activities are complete. At this stage, the data is declared as final data (database lock), and the clinical data manager hands over the data for statistical analysis. Data management activities should follow SOP procedures and support the obligation to comply with applicable laws and guidelines (such as ICH GCP and 21 CFR Part 11) when conducting data management activities. The Case Report Form (CRF) is a data collection tool for clinical trials and can be in paper or electronic format. Paper CRFs are printed, usually on carbonless paper, and sent to the research institutions conducting the clinical trials, where they are completed and then mailed back to the data management department. Electronic CRFs allow data to be directly entered into fields using a computer and transmitted electronically to the data management department. CRF design needs to consider: the information to be collected as required by the clinical trial protocol for use in statistical analysis. Where possible, standard CRFs are reusable to collect data common to most clinical trials, such as demographic information of subjects. In addition to CRF design, electronic trial design includes logic check programming. Logic checks are used to question information when inconsistent data is entered, mapping certain data points from one page of the CRF to another, or calculating fields such as the subject’s age or BMI. Logic checks help researchers enter the correct data correctly and also help improve the quality of clinical trial data. If an electronic CRF is used in a clinical trial, the database design and CRF design are closely related. Electronic CRFs can input data into a basic relational database. For clinical trials using paper CRFs, a relational database is established separately. In both cases, the relational database allows all data collected in the CRF to be gathered. Computer data validation: all computer systems used for the processing and management of clinical trials must be rigorously validated to ensure error-free operation and repeatable results. When using electronic CRFs, data entry is performed at the clinical study center by personnel who have been granted the appropriate permissions. When using paper CRFs, the pages are entered by data entry clerks. The best practice is to perform a first round of data entry, followed by a second round of entry or validation by an independent operator after the data input is complete. Any differences between the first and second rounds can be resolved, resulting in a complete and accurate reflection of the data entered on the CRF. If an operator cannot identify a piece of data, they should notify the data manager to clarify with the person who entered the data. Central laboratory data: Samples collected during the clinical trial may be sent to a central laboratory for analysis. The clinical data manager liaises with the central laboratory and agrees on the data format and transmission schedule in the data transfer protocol. The date and time of sample collection can be verified against the CRF to ensure that all collected samples have been analyzed. Other external data: The analysis of clinical trial data may be conducted by laboratories, image processing experts, or other third parties. The clinical data manager liaises with these data providers and agrees on the data format and transmission schedule. The data can be verified against the CRF to ensure consistency. Adverse event audit: The CRF collects adverse events reported during the clinical trial, but there is a separate procedure to ensure that serious adverse events are reported promptly. The clinical data manager must ensure data consistency between these procedures. Patient-recorded data: If subjects are required to record data (such as daily symptoms), diaries are provided for them to fill out. The data management of this type of data requires a different approach from CRF data, for example, it is generally impractical to question the data. Patient diaries can be in paper or electronic (electronic diary) form. This electronic diary is generally in the form of a handheld device, allowing the individual to enter the required data and transmit it to a central server. Tracking reports: Typical reports generated and used by the clinical data manager include: CRF completion status/missing pages; status of data queries; data queries not resolved within the specified time frame; common data queries (used to help identify areas for improvement). Quality control: Quality control applies to all stages of the clinical data management process and is usually governed by SOPs. Data Confidentiality and Research Outcome Ownership: Anonymization: When researchers or the funding party’s clinical coordinators handle data, they should, as much as possible, use anonymization or de-identification methods to ensure that the personal information of subjects is not identifiable in research reports or publicly released data. Data Security: Research institutions need to take appropriate technical and organizational measures to protect the data of subjects during storage and transmission, preventing unauthorized access, disclosure, loss, or destruction. Access Restrictions: Only team members directly involved in the research and the funding party’s CRC can access the personal information of subjects, and they must commit to confidentiality. Confidentiality Agreements: Researchers and all team members who may come into contact with subject information, as well as the funding party, should sign confidentiality agreements, promising not to disclose any personal information. Both the researchers and the funding party agree that all project outcomes and intellectual property rights generated or developed from conducting this study or fulfilling the research contract shall belong to Shanghai Pulmonary Hospital.

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  2024-09-06 10:48:07