ChiCTR2000031980 版本V3.2 版本创建时间2022/12/05 00:16:54 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：

 ChiCTR2000031980 

最近更新日期：

Date of Last Refreshed on：

 2022-12-05 00:12:37 

注册时间：

Date of Registration：

 1990-01-01 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

新型溶瘤病毒治疗晚期恶性实体肿瘤前瞻开放单臂对照临床研究

Public title：

A prospective, open, single-arm controlled clinical trial of novel oncolytic virus in the treatment of advanced malignant solid tumors

注册题目简写：

English Acronym：

研究课题的正式科学名称：

新型溶瘤病毒治疗晚期恶性实体肿瘤前瞻开放单臂对照临床研究

Scientific title：

A prospective, open, single-arm controlled clinical trial of novel oncolytic virus in the treatment of advanced malignant solid tumors

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：

ChiMCTR2000003215

申请注册联系人：

石玮 

研究负责人：

石玮 

Applicant：

Wei Shi 

Study leader：

Wei Shi 

申请注册联系人电话：

Applicant telephone：

 +86 18978885787

研究负责人电话：

Study leader's
telephone：

+86 18978885787

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：

 35111747@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 zhong_liping@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：

 伦审2020-009-02

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：

 2020-03-26 00:00:00

伦理委员会联系人：

方芳

Contact Name of the ethic committee：

Fang Fang

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：

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：

晚期恶性实体肿瘤  

Target disease：

Advanced malignant solid 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：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

观察新型溶瘤病毒治疗晚期恶性实体肿瘤的安全性、耐受性和有效性。  

Objectives of Study：

To observe the safety, tolerability and efficacy of a novel oncolytic viruses in the treatment of advanced malignant solid tumors.

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、自愿参加本次临床试验，理解研究程序且已签署知情同意。
2、年龄在18至80岁，男性或女性。
3、经组织/细胞学确诊的晚期恶性实体肿瘤（不可手术或转移性）并缺乏标准治疗或不具备标准治疗条件的患者。
4、Child-Pugh 肝功能评级：A级、B级。
5、根据imRECIST1.1版实体肿瘤疗效评价标准，患者具备以下条件之一：①有一处影像学（CT或MRI或PET/CT或B超）可测量病灶，要求最长径≥10 mm（若为淋巴结，则要求短轴≥15 mm）（脑转移病灶不作为唯一可测量病灶）；②转移到血液中的循环肿瘤细胞检测阳性。
6、终末期肝病模型（MELD）评分＜9分。
7、能合作观察不良事件和疗效。
8、无其他抗肿瘤伴随治疗。
9、按东部肿瘤合作组织（ECOG）标准，体能状态为0～2分。
10、血清白蛋白≥30 g/L，血清ALT≤125 U/L，血清AST≤100 U/L，血清TBIL≤1.5×ULN，电解质正常或经过治疗后达到正常，蛋白尿=0～1+，血肌酐≤1.5×ULN。
11、血常规检查标准需符合：HB≥80 g/L；ANC≥1.5×10^9/L；PLT≥70×10^9 /L。
12、患者必须从之前的治疗毒性中恢复至≤1级，除了脱发和2级既往含铂治疗相关神经病变（CTCAE 5.0）。

Inclusion criteria

1. Voluntarily participate in this clinical trial, understand the study procedures and have signed informed consent.
2. Age between 18 and 80 years old, male or female.
3. Patients with advanced malignant solid tumors (inoperable or metastatic) confirmed by histology/cytology and who lack standard treatment or do not have standard treatment conditions.
4. Child-Pugh liver function rating: A, B.
5. According to the imRECIST 1.1 version of the solid tumor efficacy evaluation criteria, the patient has one of the following conditions:
(1) There is a lesion that can be measured by imaging (CT or MRI or PET/CT or B ultrasound), and the longest diameter is >= 10 mm (if it is a lymph node); the short axis is required to be >= 15 mm) (brain metastases are not considered as the only measurable lesions);
(2) Circulating tumor cells that metastasized into the bloodstream tested positive.
6. Model of end-stage liver disease (MELD) score < 9 points.
7. Be able to cooperate to observe adverse events and curative effects.
8. No other anti-tumor accompanying therapy.
9. According to the standards of the Eastern Cancer Cooperation Organization (ECOG), the physical condition is 0 ~ 2 points.
10. Serum albumin >= 30 g/L, serum ALT <= 125 U/L, serum AST <= 100 U/L, serum TBIL <= 1.5 x ULN, normal electrolyte or reach normal after treatment, proteinuria = 0 ~ 1+, serum creatinine <= 1.5 x ULN.
11. The standard of blood routine examination should meet: HB >= 80 g/L; The ANC acuity 1.5 * 10^9 / L; PLT >= 70 x 10^9 /L.
12. Patients must recover to <= grade 1 from previous therapeutic toxicity, except for alopecia and grade 2 prior platinum-containing treatment-related neuropathy (CTCAE 5.0).

排除标准：

1、对溶瘤病毒及其代谢物或其药用辅料（不论有无活性）有过敏史者。
2、既往抗肿瘤治疗的不良反应尚未恢复到CTCAE 5.0等级评价≤1级（脱发等研究者判断无安全风险的毒性除外）。
3、曾接受免疫治疗并出现irAE等级≥3级。
4、其他未控制的活动性感染。
5、有免疫缺陷病史，包括HIV抗体检测阳性。
6、活动性乙型肝炎（HBV）或丙型肝炎病毒（HCV）感染。
7、有严重的心血管疾病史：需要临床干预的室性心律失常；QTc间期＞480ms；6个月内有急性冠脉综合征、充血性心力衰竭、脑卒中或其他III级及以上心血管事件；美国纽约心脏病协会（NYHA）心功能分级≥II级或左室射血分数（LVEF）<50％；无法控制的高血压。
8、精神障碍者或依从性差者。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。
9、妊娠期或哺乳期女性。
10、研究者认为受试者存在其它严重的系统性疾病或其他原因而不适合参加本临床研究。

Exclusion criteria：

1. Patients with a history of allergy to oncolytic viruses and their metabolites or their pharmaceutical excipients (whether active or not).
2. The adverse reactions of previous anti-tumor therapy have not been recovered to CTCAE 5.0 grade evaluation <= grade 1 (except for toxicities such as hair loss that the researchers judged to have no safety risk).
3. Received immunotherapy and had irAE grade >= 3.
4. Other uncontrolled active infections.
5. A history of immunodeficiency, including positive HIV antibody test.
6. Active hepatitis B (HBV) or hepatitis C virus (HCV) infection.
7. History of severe cardiovascular disease: ventricular arrhythmia requiring clinical intervention; QTC interval > 480ms; acute coronary syndrome, congestive heart failure, stroke or other class III or above heart disease within 6 months Vascular events; New York Heart Association (NYHA) functional class >= II or left ventricular ejection fraction (LVEF) < 50%; uncontrolled hypertension.
8. Patients with mental disorders or poor compliance. According to the judgment of the investigator, objective conditions (including the patient's psychological state, family relationship, social factors or geographical factors, etc.) prevent the patient from completing the planned study or the subjects have other factors that may cause the study to be terminated midway.
9. Women who are pregnant or breastfeeding.
10. The investigator believes that the subjects have other serious systemic diseases or other reasons and are not suitable to participate in this clinical trial.

研究实施时间：

Study execute time：

从 From 2020-02-01 00:00:00至 To 2023-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-03-01 00:00:00 至 To 2023-08-31 00:00:00

干预措施：

Interventions：

组别：

晚期恶性实体肿瘤

样本量：

 20

Group：

Advanced malignant solid tumor

Sample size：

干预措施：

新型溶瘤病毒治疗，剂量：1～3×10^7～10 pfu/kg，视病情可静脉注射，或腹腔注射、瘤内注射，也可以同时注射，每周1次，一个周期为8～12周，根据康复状况决定是否增加治疗时间。

干预措施代码：

Intervention：

Novel oncolytic virus treatment, dose: 1–3 × 10^7–10 pfu/kg. Depending on clinical status, the virus may be administered intravenously, intraperitoneally, or intratumorally, alone or in combination. Treatment is administered once weekly for 8 to 12 weeks per cycle, with treatment duration adjusted according to clinical response and recovery.

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)：

 南宁 

Country：

China

Province：

Guangxi

City：

Nanning

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 index

Type：

Primary indicator

测量时间点：

每3～4周1次

测量方法：

与研究药物有关不良反应的发生率

Measure time point of outcome：

Once every 3–4 weeks

Measure method：

Incidence of treatment-related adverse events

指标中文名：

肿瘤进展时间

指标类型：

次要指标

Outcome：

Time to progression, TTP

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观有效率

指标类型：

次要指标

Outcome：

Objective response rate, ORR

Type：

Secondary 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：

症状缓解率

指标类型：

次要指标

Outcome：

Symptom relief rate

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

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：

征募研究对象情况：

Recruiting status：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 80 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）：

未使用

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

N/A

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：

开放

Blinding：

Open-label

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)：

Not stated

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： 研究病历为最原始记录，必须妥善保存。本研究采用电子病例报告表进行数据的采集。病例报告表来自研究病历，由研究者完成。每个筛选和入选病例必须完成病例报告表。研究者将确保数据采集的准确性和可靠性。所有数据都将采用基于因特网的电子CRF加以记录，在线自动检查数据的完整性。输入用户名和密码后可获取研究数据，用户应严格保密自己的密码。 服务器和用户个人电脑之间的电子通讯是加密的，不会传输被保护的数据(患者姓名、地址、身份证号等)。对于研究数据的所有更改，可获得完整的审核跟踪。实验室数据将采用取决于中心和性别的正常值范围加以确认。描述性和逻辑性数据检查在不断完善的数据库中进行，任何不合理或不一致的数据输入将告知研究单位和/或监查人员，由研究单位的工作人员加以解释和纠正。研究者必须对患者毒性反应分级及肿瘤疗效反应作出决定，而主要研究者应该对诊断作出最后判断。 在研究过程中，研究者应允许申办方的监查人员或代表到研究机构检查研究相关文件(如病人知情同意书、研究药物清点表、伦理委员会的批准文件)。监查人员到访时会对病人的档案进行严格审阅，以核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、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。纸质资料由专人管理。 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 collection: Research medical records are the most original records and must be kept properly. In this study, electronic case report form is used for data collection. The case report form comes from the study medical record and is completed by the investigator. A case report form must be completed for each selected and selected case. Researchers will ensure the accuracy and reliability of data collection. All data will be recorded using an Internet-based electronic CRF, which automatically checks the integrity of the data online. After entering the user name and password, the research data can be obtained. Users should keep their passwords strictly confidential. Electronic communications between the server and the user's PC are encrypted and do not transmit protected data (patient names, addresses, ID numbers, etc.). A complete audit trail is available for all changes to the study data. Laboratory data will be confirmed using a range of normal values depending on centre and sex. Descriptive and logical data checks are carried out in the continuously improving database, and any unreasonable or inconsistent data entry will be informed to the research unit and/or the monitoring staff, who will interpret and correct it. The investigator must decide on the patient's toxicity grade and tumor efficacy response, and the principal investigator should make the final judgment on the diagnosis. During the study, the investigator should allow sponsors' monitors or representatives to visit the study facility to review study related documents (e.g., patient informed consent, study drug inventory, ethics committee approval documents). During the visit, the patient's file is carefully reviewed to check whether the information recorded on the CRF, especially key information regarding safety and efficacy, matches the patient's original records. Data Management: 1. Establish a data management committee. Skilled computer operators were recruited to form a data management committee, which was headed by members of the research group. Other data managers were unaware of the research scheme. 2. Data preservation and entry. All subjects' data and scale data are recorded by DDC team members on the computer, and all original data are recorded and saved in the subject database, the input content of which is consistent with the original data. The paper materials are managed by special personnel. 3. Data quality control and backup. Members of the research group regularly conducted quality control over the input data, timely reported and recorded missing data items, and recalibrated and calibrated the obviously wrong data. Periodically export and back up 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：

  2020-04-16 22:27:52