中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2200066334
最近更新日期： Date of Last Refreshed on：	2023-06-11 00:51:46
注册时间： Date of Registration：	2022-12-01 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	特瑞普利单抗及仑伐替尼联合SBRT与肝动脉持续灌注治疗不可切除的肝癌合并门静脉主干癌栓的有效性及安全性
Public title：	Toripalimab and Lenvatinib combined with SBRT and HAIC for HCC With Portal Vein Invasion：A single-arm, single-center clinical study
注册题目简写：
English Acronym：
研究课题的正式科学名称：	特瑞普利单抗及仑伐替尼联合SBRT与肝动脉持续灌注治疗不可切除的肝癌合并门静脉主干癌栓的有效性及安全性
Scientific title：	toripalimab and lenvatinib combined with SBRT and HAIC for HCC With Portal Vein Invasion：A single-arm, single-center clinical study
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：	罗靖茹	研究负责人：	林海锋
Applicant：	Jingru Luo	Study leader：	Haifeng Lin
申请注册联系人电话： Applicant telephone：	+86 177 8984 6883	研究负责人电话： Study leader's telephone：	+86 133 2206 0949
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：	ruru555@126.com	研究负责人电子邮件： Study leader's E-mail：	13322060949@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：	海南省海口市龙华区椰海大道368号	研究负责人通讯地址：	海南省海口市龙华区椰海大道368号
Applicant address：	368 Yehai Dadao, Longhua District, Haikou, Hainan	Study leader's address：	368 Yehai Dadao, Longhua District, Haikou, Hainan
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：	海南医学院第二附属医院
Applicant's institution：	The Second Affiliated Hospital of Hainan Medical College
研究负责人所在单位：	海南医学院第二附属医院
Affiliation of the Leader：	The Second Affiliated Hospital of Hainan Medical College

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：	2022-11-01	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：	海南医学院第二附属医院医学伦理委员会
Name of the ethic committee：	Ethics Committee of the Second Affiliated Hospital of Hainan Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2022-08-26 00:00:00
伦理委员会联系人：	欧辉运
Contact Name of the ethic committee：	HuIyun Ou
伦理委员会联系地址：	海南省海口市龙华区椰海大道368号
Contact Address of the ethic committee：	368 Yehai Dadao, Longhua District, Haikou, Hainan
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 898 6680 9348	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：

海南医学院第二附属医院

Primary sponsor：

The Second Affiliated Hospital of Hainan Medical College

研究实施负责（组长）单位地址：

海南省海口市龙华区椰海大道368号

Primary sponsor's address：

368 Yehai Dadao, Longhua District, Haikou, Hainan

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	海南	市(区县)：	海口
Country：	CHINA	Province：	Hainan	City：	Haikou
单位(医院)：	海南医学院第二附属医院	具体地址：	海南省海口市龙华区椰海大道368号
Institution hospital：	The Second Affiliated Hospital of Hainan Medical College	Address：	368 Yehai Dadao, Longhua District, Haikou, Hainan

经费或物资来源：

自筹经费

Source(s) of funding：

self-financing

研究疾病：

原发性肝癌

Target disease：

HCC

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期临床试验

Study phase：

2

研究设计：

单臂

Study design：

Single arm

研究目的：

评估特瑞普利单抗及仑伐替尼联合SBRT与肝动脉持续灌注治疗晚期肝细胞癌的6个月OS率。

Objectives of Study：

To evaluate the 6-month overall survival (OS) rate of Toripalimab and lenvatinib combined with SBRT and continuous hepatic arterial infusion in the treatment of advanced hepatocellular carcinoma (HCC)

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Age range from 18 to 75 years old, regardless of gender;
2. For BCLC stage C hepatocellular carcinoma that has been clearly diagnosed by pathology or clinically diagnosed, if the clinical diagnosis is not typical, pathological diagnosis is required;
3. Two imaging studies have confirmed that only the main portal vein invasion (Vp4) exists.
4. Patients who have not received local anti-tumor therapy for hepatocellular carcinoma within 4 weeks prior to enrollment can be enrolled if they have received local anti-tumor therapy for hepatocellular carcinoma in neoadjuvant therapy;
5. Have not received systemic anti-tumor therapy for hepatocellular carcinoma in the past, including chemotherapy, Targeted therapy and immunotherapy;
6. At least one measurable lesion (according to mRECIST standard);
7. The laboratory test meets the following requirements: Platelets>=50 × 109/L; Hemoglobin>=9g/dL; White blood cells>=4 × 109/L; Neutrophils>=1.5 × 109/L); Serum total bilirubin<=1.5 times the upper limit of normal value (ULN), Transaminase (ALT, AST)<=5 times ULN; Creatinine<=1.5 times ULN; Urinary routine results showed that urinary protein<2+; For patients with baseline urine routine testing showing urinary protein>=2+, 24-hour urine collection should be performed and 24-hour urine protein quantification<1g; International standardized ratio (INR) or activated partial thromboplastin time (APTT)<=1.5 times ULN;
8. Child Pugh grading A-B;
9. ECOG score of 0 or 1;
10. The expected survival period is greater than or equal to 3 months;
11. Sign a written informed consent form and be willing to undergo follow-up.

排除标准：

1.有其他恶性肿瘤病史，已治愈的宫颈原位癌或皮肤基底细胞癌除外; 2.已知异体器官或异体造血干细胞移植史的患者; 3.存在任何活动性自身免疫病或有自身免疫病病史; 4.乙型肝炎病毒(HBV)DNA > 2000IU/ml 或 104 拷贝/ml;丙型肝炎病毒(HCV)RNA >103 拷贝/ml;乙肝表面抗原(HbsAg)与抗 HCV 抗体同时阳性; 人免疫缺陷病毒(HIV)感染者(HIV 1/2 抗体阳性); 5.入组前6个月内发生任何危及生命的出血事件; 6.处于活动期或临床控制不佳的严重感染或在入组前14天内有重度感染; 7.患有II级以上心肌缺血或心肌梗塞、控制不良的心律失常(包括 QTcF 间期男性>=450ms、女性>=470ms)(QTc 间期以 Fridericia 公式计算);按照 NYHA 标准II级以上心功能不全或心脏彩超检查:LVEF(左室射血分数)<50%; 8.高血压患者，经降压药物治疗无法获得良好控制(收缩压>150mmHg，舒张压>100mmHg); 9.未控制的胸腔积液、心包积液，或中等量以上腹水; 10.尿常规显示尿蛋白>=2+且证实 24 小时尿蛋白定量>1.0 g; 11.活动性或未能控制的严重感染，首次给药前发生原因不明的发热(体温>38.5°C); 12.糖尿病控制不佳(空腹血糖(FBG)>10mmol/L); 13.目前或既往有中枢神经系统转移; 14.在参加本研究前的2个月内出现过腹部瘘管、胃肠道穿孔或腹腔脓肿; 15.已知存在的遗传性或获得性出血及血栓倾向; 16.既往6个月内发生过血栓/栓塞事件; 17.无法吞咽、慢性腹泻或肠梗阻，明显影响药物服用和吸收; 18.入组前 30 天内接受过任何疫苗治疗(包括抗感染疫苗，如流感疫苗、水痘疫苗等); 19.在过去两年内有任何药物(包括精神类药物)或酒精依赖或滥用史; 20.对含碘造影剂严重过敏的患者; 21.已知对任何单克隆抗体、抗血管生成靶向药物、化疗等本研究药物成分有严重过敏史; 22.孕妇或哺乳期妇女; 23.经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素。 24.入组前4周参加过临床试验。

Exclusion criteria：

1. Have a history of other malignant tumors, except for cured cervical Carcinoma in situ or skin Basal-cell carcinoma; 2. Patients with a known history of allogeneic organ or hematopoietic stem cell transplantation; 3. Existence of any active autoimmune disease or history of autoimmune disease; 4. Hepatitis B virus (HBV) DNA>2000IU/ml or 104 copies/ml; Hepatitis C virus (HCV) RNA>103 copies/ml; Hepatitis B surface antigen (HbsAg) and anti HCV antibody were positive at the same time; People infected with Human Immunodeficiency Virus (HIV) (HIV 1/2 antibody positive); 5. Any life-threatening bleeding event occurs within 6 months prior to enrollment; 6. Severe infections during the active period or under poor clinical control, or severe infections within 14 days prior to enrollment; 7. Suffering from myocardial ischemia or myocardial infarction of grade II or above, and poorly controlled arrhythmia (including QTcF interval for males>=450ms and females>=470ms) (QTc interval is calculated using Fridericia formula); According to NYHA standard, cardiac insufficiency above grade II or color Doppler echocardiography: LVEF (left ventricular Ejection fraction)<50%; 8. Hypertensive patients who cannot achieve good control through antihypertensive medication treatment (systolic blood pressure>150mm Hg, diastolic blood pressure>100mmHg); 9. Uncontrolled Pleural effusion, pericardial effusion, or more than moderate amount of ascites; 10. Urinary routine examination shows urinary protein>=2+and confirms that 24-hour urine protein quantification is>1.0 g; 11. Active or uncontrollable severe infection, with unexplained fever (body temperature>38.5 ° C) occurring before the first administration; 12. Poor control of diabetes (Glucose test#Fasting blood sugar (FBG)>10mmol/L); 13. Current or previous central nervous system metastasis; 14. Has experienced abdominal fistula, gastrointestinal perforation, or abdominal abscess within 2 months prior to participating in this study; 15. Known genetic or acquired bleeding and thrombotic tendencies; 16. Have experienced thrombosis/embolism events within the past 6 months; 17. Inability to swallow, chronic diarrhea or Bowel obstruction, which significantly affects drug administration and absorption; 18. Have received any vaccine treatment (including anti infection vaccine, such as influenza vaccine, Varicella vaccine, etc.) within 30 days before enrollment; 19. Have any history of drug (including psychotropic substances) or Alcohol dependence or abuse in the past two years; 20. Patients with severe allergies to iodine containing contrast agents; 21. It is known that there is a history of severe allergies to any monoclonal antibodies, anti angiogenic targeted drugs, chemotherapy, or other components of this study drug; 22. Pregnant or lactating women; 23. According to the judgment of the researcher, there are other factors that may cause the study to be terminated midway. 24. Participated in clinical trials 4 weeks before enrollment.

研究实施时间：

Study execute time：

从 From 2022-09-01 00:00:00至 To 2025-08-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-12-01 00:00:00 至 To 2024-08-31 00:00:00

干预措施：

Interventions：

组别：	单臂研究	样本量：	20
Group：	single arm	Sample size：	20
干预措施：	特瑞普利单抗及仑伐替尼联合SBRT与肝动脉持续灌注治疗	干预措施代码：
Intervention：	Toripalimab and lenvatinib combined with SBRT and continuous hepatic arterial infusion	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	海南	市(区县)：
Country：	China	Province：	Hainan	City：
单位(医院)：	海南医学院第二附属医院	单位级别：	三甲
Institution hospital：	The Second Affiliated Hospital of Hainan Medical College	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：	次要指标
Outcome：	Progression Free Surviva	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	客观缓解率	指标类型：	次要指标
Outcome：	Overall Response 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：	缓解持续时间	指标类型：	次要指标
Outcome：	Duration of Response	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	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总生存期	指标类型：	次要指标
Outcome：	Overall Survival	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	安全性	指标类型：	副作用指标
Outcome：	Safety	Type：	Adverse events
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	6个月OS率	指标类型：	主要指标
Outcome：	6-month overall survival (OS) rate	Type：	Primary 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：

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）：

不适用

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：
Blinding：

是否共享原始数据： IPD sharing	否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）：	试验完成后6个月内公开
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Within six months after the trail comolete
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：	本课题将使用EDC系统进行数据采集录入。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	This study will use the EDC system for data acquisition and entry.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2022-12-01 16:02:36