ChiCTR2100043644 版本V1.1 版本创建时间2021/06/19 23:19:04 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：

 ChiCTR2100043644 

最近更新日期：

Date of Last Refreshed on：

 2021-06-19 23:15:21 

注册时间：

Date of Registration：

 2021-02-24 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

新型溶瘤病毒抗恶性肿瘤CTC微转移的前瞻、开放、单臂对照临床研究

Public title：

Novel oncolytic virus treatment in patients with CTC micrometastasis: a prospective, open, single-arm, phase II trial

注册题目简写：

English Acronym：

研究课题的正式科学名称：

新型溶瘤病毒抗恶性肿瘤CTC微转移的前瞻、开放、单臂对照临床研究

Scientific title：

Novel oncolytic virus treatment in patients with CTC micrometastasis: a prospective, open, single-arm, phase II trial

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：

李春姗 

研究负责人：

李春姗 

Applicant：

Chunshan Li 

Study leader：

Chunshan Li 

申请注册联系人电话：

Applicant telephone：

 +86 18507810785

研究负责人电话：

Study leader's
telephone：

+86 18507810785

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：

 pingting4746zhong@163.com

研究负责人电子邮件：

Study leader's E-mail：

 pingting4746zhong@163.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 Zhuang Autonomous Region, China

Study leader's address：

89-9 Dongge Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, 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：

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：

 2020-049-02

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：

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：

 2021-01-29 00:00:00

伦理委员会联系人：

黎老师

Contact Name of the ethic committee：

Mr. Li

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 Zhuang Autonomous Region, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 0771-5323553

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 Zhuang Autonomous Region, 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：

各种恶性肿瘤  

Target disease：

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：

 II-III期临床试验 

Study phase：

2-3

研究设计：

单臂 

Study design：

Single arm 

研究目的：

观察新型溶瘤病毒抗恶性肿瘤CTC微转移的有效性、安全性和耐受性。  

Objectives of Study：

observe the new oncolytic virus anti CTC micrometastasis of the efficacy, safety and tolerability of the drug were evaluated.

药物成份或治疗方案详述：

经病理学检查确诊为原发性肝癌、乳腺癌等恶性实体肿瘤的在院或门诊病人共60例。治疗前后收集观察指标 并完善实验室检查项目，治疗后随访安全性指标和有效性指标。 新型溶瘤病毒制剂：1~3×107-10pfu/kg，静脉注射，或腹腔注射，也可以同时注射，每周一次，连续用8-12周。  

Description for medicine or protocol of treatment in detail：

A total of 60 patients with primary liver cancer, lung cancer and other malignant solid tumors confirmed by pathological examination. New oncolytic virus preparation: 1 ~ 3 × 107-10pfu / kg, intravenous injection, or intraperitoneal injection, or at the same time, once a week, for 8-12 weeks.  

纳入标准：

1）18 周岁≤年龄≤75 周岁，性别不限；
2）经组织病理学诊断为肝癌、乳腺癌等恶性实体肿瘤的患者；
3）术后或末次化疗/放疗后1月以上血循环肿瘤细胞仍阳性的患者；
4）体能状态评分 ECOG 0-2分；
5）预计生存期≥ 3 个月；
6）实验室检查：中性粒细胞≥1.5×10^9/L；血小板≥100×10^9/L；血红蛋白≥90g/L；
肝肾功能正常；
7）既往 5 年内无第二肿瘤；
8）能理解本研究的情况，患者及（或）法定代理人自愿同意参加本试验并签署知情同意书。

Inclusion criteria

1）18 years old ≤ age ≤ 75 years old, regardless of gender;
2）Patients with malignant solid tumors such as liver cancer and lung cancer were diagnosed by histopathology;
3）The patients with stage I-III after operation, and the circulating tumor cells were still positive more than 1 month after operation or the last chemotherapy / radiotherapy;
4）ECoG score was 0-2;
5）The expected survival time was more than 3 months;
6）Laboratory examination: neutrophils ≥ 1.5 × 109 / L; platelets ≥ 100 × 109 / L; hemoglobin ≥ 90g / L;
The liver and kidney function were normal;
7）There was no second tumor in the past 5 years;
8）The patient and / or legal representative voluntarily agreed to participate in the trial and signed the informed consent.

排除标准：

排除标准
1）在首次给药前30 天内服用过其他正在临床试验的药物；
2）近5年内被诊断第二发肿瘤者；
3）首次使用研究药物之前2周内有明显创伤性损伤者；受试者在研究期间可能会接受其他抗肿瘤治疗导致无法继续本研究；
4）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；
5）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）；
6）按NYHA标准，III~IV 级心功能不全者；
7）基线期心电图QTc 延长者（QTcF：男性>450 ms，女性>470 ms）；
8）任何以下心脏标准：a)筛选期静息心电图（ECG）显示校正QT间期（QTc）＞470毫秒； b)静息ECG结果显示的任何有重要临床意义的节律、传导或形态的异常，如完全性左束支传导阻滞，Ⅱ度及以上心脏传导阻滞，PR间期＞250毫秒等； c)任何增加QTc延长风险或心律失常风险的因素，如心衰、低钾血症、先天性长QT综合症、长QT综合症家族史或一级亲属中有小于40岁发生无法解释的猝死、使用任何已知可延长QT间期的伴随药物；
9）任何无法控制的严重的与临床研究相关的问题（例如物质滥用，不受控制的精神病状态，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、及合并治疗或实验室检查异常者；
14）根据研究者的判断，有严重的危害患者安全、或影响患者完成本研究的伴随疾病（如控制不佳的高血压、严重的糖尿病、甲状腺疾病等
15）妊娠期或哺乳期女性；
16）自身免疫疾病

Exclusion criteria：

1）Other drugs in clinical trials were taken within 30 days before the first administration;
2）The second tumor was diagnosed in recent 5 years;
3）Patients with obvious traumatic injury within 2 weeks before the first use of the study drug; subjects may receive other anti-tumor treatment during the study period, resulting in unable to continue the study;
4）Subjects with active gastrointestinal diseases or other diseases may lead to factors that significantly affect drug absorption, distribution, metabolism or excretion;
5）Uncontrollable chronic systemic comorbid diseases (such as severe chronic lung, liver, kidney or heart disease);
6）According to NYHA standard, patients with grade III-IV cardiac insufficiency;
7）QTc prolongation of baseline ECG (QTCF: male > 450 ms, female > 470 MS);
8）Any disease factor that increases the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia and congenital long QT syndrome;
9）Any uncontrollable serious clinical study related problems (e.g., substance abuse, uncontrolled psychiatric state, uncontrolled complications, including active infections, arterial thrombosis, and symptomatic pulmonary embolism);
10）Previous history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or evidence of interstitial lung disease during any period of clinical activity;
11）The subjects were in the stage of acute infection and needed drug treatment and antiviral treatment;
12）The subjects were positive for HIV, HBV and HCV (HBV copies ≥ 104 copies / ml, HCV copies ≥ 103 copies / ml);
13）According to the judgment of the researcher, the objective conditions (including the patient's psychological state, family relationship, social or geographical factors, etc.) make the patient unable to complete the planned study, or the subject has other factors that may lead to the termination of the study, and the abnormal combination treatment or laboratory examination;
14）According to the judgment of the researchers, there are some concomitant diseases (such as poorly controlled hypertension, severe diabetes, thyroid disease, etc.) that seriously endanger the safety of patients or affect the completion of this study
15）Pregnant or lactating women;
16）Autoimmune diseases

研究实施时间：

Study execute time：

从 From 2020-12-31 00:00:00至 To 2022-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2021-03-01 00:00:00 至 To 2022-12-31 00:00:00

干预措施：

Interventions：

组别：

干预组

样本量：

 20

Group：

experimental group

Sample size：

干预措施：

新型溶瘤病毒：1×10^7-9 PFU/Kg，静脉注射，或腹腔注射，也可以同时注射，每周一次，连续用 8-12 周。

干预措施代码：

Intervention：

New oncolytic virus: 1×10^7~9 PFU/Kg, intravenous injection, or intraperitoneal injection, or at the same time, once a week, for 8-12 weeks.

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)：

  

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

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

Type：

Primary 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：

无病生存期

指标类型：

次要指标

Outcome：

Disease-free survival (DFS)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存时间

指标类型：

次要指标

Outcome：

Overall survival time (OS)

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 (QOL)

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：

标本中文名：

尿液

组织：

Sample Name：

urine

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

标本中文名：

粪便

组织：

Sample Name：

feces

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）：

单臂、自身前后对照

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

Single arm, before and after control

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：

单臂试验是开放、前后对照试验，不是盲法。

Blinding：

The single-arm test is an open, before and after controlled test, not a blind method.

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)：

The original data is reported to the Ministry of Science and Technology for system sharing

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：

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：

  2021-02-24 08:52:28