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人EGFR/ALK基因突变联合检测试剂盒(杂交捕获测序法)
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注册号:

Registration number:

ChiCTR2000039940 

最近更新日期:

Date of Last Refreshed on:

2021-02-21 

注册时间:

Date of Registration:

2020-11-14 

注册号状态:

补注册  

Registration Status:

Retrospective registration  

注册题目:

人EGFR/ALK基因突变联合检测试剂盒(杂交捕获测序法) 

Public title:

Human EGFR/ALK Mutation Combo Detection Kit (Hybrid Capture-Based Next Generation Sequencing) 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

人EGFR/ALK基因突变联合检测试剂盒(杂交捕获测序法)(HPLS2019-01) 

Scientific title:

Human EGFR/ALK Mutation Combo Detection Kit (Hybrid Capture-Based Next Generation Sequencing) (HPLS2019-01) 

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:

职小玲 

研究负责人:

王翠翠 

Applicant:

Xiaoling Zhi 

Study leader:

Cuicui Wang 

申请注册联系人电话:

Applicant telephone:

+86 13820662309 

研究负责人电话:

Study leader's telephone:

+86 13269211794 

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:

zhixl@haplox.com 

研究负责人电子邮件:

Study leader's E-mail:

wangcc@haplox.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:

北京市大兴区荣华街道林肯公园C区4栋803室 

研究负责人通讯地址:

北京市大兴区荣华街道林肯公园C区4栋803室 

Applicant address:

Room 803, Building 4, Zone C, Link Park, Ronghua Street, Daxing District, Beijing, China 

Study leader's address:

Room 803, Building 4, Zone C, Link Park, Ronghua Street, Daxing District, Beijing, 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:

深圳市海普洛斯生物科技有限公司 

Applicant's institution:

HaploX Biotechnology Co., Ltd. 

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:

(2019)年临审第(09)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:

首都医科大学附属北京胸科医院伦理委员会 

Name of the ethic committee:

Ethics Committee of Beijing Chest Hospital affiliated to Capital Medical University 

伦理委员会批准日期:

Date of approved by ethic committee:

2019-03-11 

伦理委员会联系人:

张彤群 

Contact Name of the ethic committee:

Tongqun Zhang 

伦理委员会联系地址:

北京市通州区北马场97号 

Contact Address of the ethic committee:

97 North Machang Road, Tongzhou District, Beijing, 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:

首都医科大学附属北京胸科医院 

Primary sponsor:

Beijing Chest Hospital Affiliated to Capital Medical University 

研究实施负责(组长)单位地址:

北京市通州区北马场97号 

Primary sponsor's address:

97 North Machang Road, Tongzhou District, Beijing, 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):

广东

市(区县):

深圳

Country:

China

Province:

Guangdong

City:

Shenzhen

单位(医院):

深圳市海普洛斯生物科技有限公司

具体地址:

南山区西丽街道松坪山路3号奥特迅电力大厦8楼

Institution
hospital:

Shenzhen haplus Biotechnology Co., Ltd

Address:

Eighth Floor, Auto Electric Power Building, 3 Songpingshan Road, Xili Street, Nanshan District

经费或物资来源:

深圳市海普洛斯生物科技有限公司 

Source(s) of funding:

Shenzhen haplus Biotechnology Co., Ltd 

研究疾病:

非小细胞肺癌 

Target disease:

Non-small cell lung cancer 

研究疾病代码:

 

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:

研究目的:

本临床试验采用盲法、对照试验设计,对筛选的临床诊断为非小细胞肺癌的福尔马林固定石蜡包埋(FFPE)样本(以下简称样本)进行检测。采用深圳市海普洛斯生物科技有限公司研制的人 EGFR/ALK 基因突变联合检测试剂盒(杂交捕获测序法)进行检测,采用罗氏公司 cobas EGFR Mutation Test V2 和雅培公司 ALK 基因重组检测试剂盒(荧光原位杂交法)作为对照,进行盲法检测。且对两种方法检测结果不一致的组织样本,采用一代测序进行复核。 选取部分经深圳市海普洛斯生物科技有限公司研制的人 EGFR/ALK 基因突变联合检测试剂盒(杂交捕获测序法)检测结果为 T790M、L858R、19del 缺失突变阳性或者ALK 融合突变,且有相关服用靶向用药信息的患者进行药物疗效相关性研究,以验证TKI 药物疗效的有效性以及人 EGFR/ALK 基因突变联合检测试剂盒(杂交捕获测序法)的准确性,其中 19del 缺失或 L858R 突变阳性的患者可使用 EGFR 靶向药物盐酸埃克替尼片/吉非替尼片;T790M 突变阳性的患者可使用甲磺酸奥希替尼片;ALK 融合突变的患者可使用克唑替尼胶囊。 通过以上的比较分析,评估深圳市海普洛斯生物科技有限公司研制的人 EGFR/ALK基因突变联合检测试剂盒(杂交捕获测序法)在临床检测中的适用性、准确性、有效性以及是否具备实际应用价值。并通过临床试验对临床前制定的各项指标进行修正;发现或预测在实际应用中遇到的问题,以便在说明书增加相关警告或提示,以提高用户操作规范性。 

Objectives of Study:

In this clinical trial, a blind, controlled trial design is used to detect the selected formalin fixed paraffin embedded (FFPE) samples (hereinafter referred to as samples) clinically diagnosed as non-small cell lung cancer. The human EGFR / ALK gene mutation detection kit (hybridized capture sequencing) developed by Shenzhen haplus Biotechnology Co., Ltd. is used for detection, and the Roche Cobas EGFR mutation test V2 and Abbott ALK gene recombination detection kit (fluorescence in situ hybridization) are used as controls for blind detection. The tissue samples with inconsistent detection results of the two methods are checked by first generation sequencing. In order to verify TKI, we select some patients with T790M, L858R, 19del deletion mutation or ALK fusion mutation and relevant targeted medication information developed by Shenzhen haplus Biotechnology Co., Ltd. (hybridized capture sequencing) Among them, patients with 19del deletion or L858R mutation positive can use EGFR targeted drug icotinib hydrochloride tablets / gefitinib tablets; patients with T790M mutation positive can use oxitinib mesylate tablets; patients with al790m mutation positive can use EGFR targeted drug icotinib hydrochloride tablets / gefitinib tablets Patients with fusion mutation can use clotriminib capsules. Through the above comparative analysis, the applicability, accuracy, effectiveness and practical application value of the human EGFR / ALK gene mutation joint detection kit (hybridized capture sequencing) developed by Shenzhen haplus Biotechnology Co., Ltd. in clinical detection are evaluated. And through clinical trials, we can revise the pre clinical indicators, discover or predict the problems encountered in practical application, so as to add relevant warnings or prompts in the manual, so as to improve the standardization of user operation. 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

析因分组(即根据危险因素或暴露因素分组) 

Study design:

Factorial 

纳入标准:

(1) 选择年龄≥18 周岁,性别不限; (2) 临床上经细胞学或组织学诊断为非小细胞肺癌(NSCLC)的受试者; (3) 蜡卷 10 片以上,厚度 3-5μm 的样本,白片 2 片以上,肿瘤细胞占比≥20%,坏死组织区域<10%。 (4) 选择 2 年以内的样本; (5) 干扰样本:小细胞肺癌或良性肿瘤的样本。 

Inclusion criteria

1. Subjects aged 18 years or above were selected, regardless of gender; 2. Subjects with clinically diagnosed non-small cell lung cancer (NSCLC) by cytology or histology; 3. More than 10 pieces of wax roll, 3-5 μ m thick samples, more than 2 pieces of white pieces, tumor cells accounted for more than 20%, necrosis tissue area < 10%. 4. Select samples within 2 years; 5. Interference samples: samples of small cell lung cancer or benign tumor. 

排除标准:

(1) 样本量不足,达不到检测要求的样本; (2) 未按照说明书要求进行保存的样本; (3) 病例信息不完整的样本;(包括性别、年龄、诊断结果、影像学诊断、病理诊断和其他人口学资料等) (4) 研究者认为需要排除的样本。 

Exclusion criteria:

1. The sample size is insufficient to meet the test requirements; 2. Samples not kept in accordance with the instructions; 3. Samples with incomplete case information (including gender, age, diagnosis results, imaging diagnosis, pathological diagnosis and other demographic data, etc.) 4. Samples that the researchers think need to be excluded. 

研究实施时间:

Study execute time:

From2019-04-17To 2020-03-31 

征募观察对象时间:

Recruiting time:

From2019-04-17To 2020-03-31 

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):

金标准:一代测序; 参考标准:cobas EGFR Mutation Test V2 (罗氏诊断公司,国械注进20193401515)和ALK 基因重组检测试剂盒(荧光原位杂交法)(雅培公司 ,国械注进20143405183)

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):

Gold Standard: Sanger sequencing Reference Standard:cobas EGFR Mutation Test V2 (Roche Diagnostics GmbH,State instrument injection 20193401515) and Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular, Inc.,State instrument injection 20143405183).

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):

本试剂盒(人 EGFR/ALK基因突变联合检测试剂盒(杂交捕获测序法))基于高通量测序法(NGS)用于定性检测人的非小细胞肺癌(NSCLC)的福尔马林固定石蜡包埋(FFPE)病理标本样本中所提取 DNA 的 EGFR 基因的 3 种突变以及ALK 基因的 1 种基因融合,共计 4 种体细胞变异(19 外显子缺失、L858R 突变、T790M 突变和ALK 融合突变)。本试剂盒仅用于 NSCLC 患者靶基因序列的检测,检测结果仅供临床参考。其中 19 外显子缺失、L858R 突变 用于盐酸埃克替尼片/吉非替尼片的伴随诊断检测,T790M 突变用于甲磺酸奥希替尼片的伴随诊断检测,ALK 融合突变用于克唑替尼胶囊的伴随诊断检测。

Index test:

Human EGFR/ALK Mutation Combo Detection Kit (Hybrid Capture-Based Next Generation Sequencing)

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)

非小细胞肺癌患者

例数:

Sample size:

1022

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):

Patients with non-small cell lung cancer (NSCLC).

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):

小细胞肺癌或良性肿瘤的样本

例数:

Sample size:

28

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

Small cell lung cancer or benign tumor samples.

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

北京 

市(区县):

北京 

Country:

China 

Province:

Beijing 

City:

Beijing 

单位(医院):

首都医科大学附属北京胸科医院 

单位级别:

三级甲等 

Institution
hospital:

Beijing Chest Hospital Affiliated to Capital Medical University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

河南 

市(区县):

郑州 

Country:

China 

Province:

He'nan 

City:

Zhengzhou 

单位(医院):

河南省肿瘤医院 

单位级别:

三级甲等 

Institution
hospital:

He'nan Cancer Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

山西 

市(区县):

太原 

Country:

China 

Province:

Shanxi 

City:

Taiyuan 

单位(医院):

山西省肿瘤医院 

单位级别:

三级甲等 

Institution
hospital:

Shanxi Cancer Hospital  

Level of the institution:

Tertiary A 

测量指标:

Outcomes:

指标中文名:

阳性符合率

指标类型:

主要指标 

Outcome:

Positive coincidence 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:

阴性符合率

指标类型:

主要指标 

Outcome:

Negative coincidence 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:

总符合率

指标类型:

主要指标 

Outcome:

The total coincidence 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:

Kappa值

指标类型:

主要指标 

Outcome:

Kappa value

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

客观缓释率

指标类型:

附加指标 

Outcome:

Objective Response Rate

Type:

Additional 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:

附加指标 

Outcome:

disease control rate

Type:

Additional 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:

福尔马林固定石蜡包埋样本

组织:

Sample Name:

Formalin fixed paraffin embedded samples

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:

结束

Completed

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age 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):

不适用

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

N/A

盲法:

样本入组完成后将样本进行设盲,由主要研究者授权的研究者对样本进行设盲并记录保存。设盲规则如下(从左到右): 第1-2位:研究单位ID(01-03); 第3-5位:样本ID(001-999); 例如:标签01001,指研究单位01中心入选的第一个样本。 设盲人员将对样本的盲号进行登记,设盲文件将有设盲人员独立保存直至揭盲。

Blinding:

After the samples were enrolled, the samples were blinded and recorded by the researchers authorized by the main researcher. Let the blind rule be as follows (from left to right) 1-2: research unit ID (01-03); 3-5: sample ID (001-999); For example, label 01001 refers to the first sample selected by research unit 01 center. The blind person will register the blind number of the sample, and the blind document will be kept by the blind person independently until it is unblinded.

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):

暂不到期,不公开 请阅读网页注册指南中关于 原始数据共享 的内容。

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

Not expired, not open

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:

数据采集和源文件: 本研究将会按照标准化的病例报告表(CRF)和/或其他数据收集形式来采集研究数据。所有研究中心的现场都会提供这些数据收集表单以备用。 研究人员将信息录入表单中,确保信息的完整性和准确性。如果出现任何需要更正的错误,需要修改应按照填写说明进行规范操作,并同时签署修改者的姓名及修改日期。 数据管理: 包括数据的收集、清理和数据库锁定等,并提交给统计部门进行分析。

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

Data acquisition and source files: The study data will be collected in accordance with the standardized case Report Form (CRF) and/or other data collection formats.These data collection forms are available on site at all research centers for standby use. Researchers enter information into forms to ensure completeness and accuracy.If there are any errors that need to be corrected, please follow the instructions and sign the name and date of modification. Data management: Includes data collection, cleaning and database locking, and submits to statistical department for analysis.

数据与安全监察委员会:

Data and Safety Monitoring Committee:

无/No

注册人:

Name of Registration:

 2020-11-14
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