ChiCTR2300073889 版本V1.2 版本创建时间2026/03/31 17:51:47 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：

 ChiCTR2300073889 

最近更新日期：

Date of Last Refreshed on：

 2023-09-17 12:16:36 

注册时间：

Date of Registration：

 2023-07-24 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

BCLC B/C期肝细胞癌行经肝动脉栓塞化疗（TACE）联合信迪利单抗和贝伐珠单抗类似物治疗降为BCLC A期后接受手术切除或射频消融对比持续药物治疗的随机、对照临床试验

Public title：

A randomized, controlled clinical trial comparing surgery or radiofrequency ablation following a downgrade to BCLC stage A from BCLC stages B/C after treatment with Transarterial chemoembolization (TACE) combined with Cyndi single-antibody and Bevacizumab analogs, against continuous drug therapy

注册题目简写：

English Acronym：

研究课题的正式科学名称：

BCLC B/C期肝细胞癌行经肝动脉栓塞化疗（TACE）联合信迪利单抗和贝伐珠单抗类似物治疗降为BCLC A期后接受手术切除或射频消融对比持续药物治疗的随机、对照临床试验

Scientific title：

A randomized, controlled clinical trial comparing surgery or radiofrequency ablation following a downgrade to BCLC stage A from BCLC stages B/C hepatocellular carcinoma after treatment with Transarterial chemoembolization (TACE) combined with sintilimab and Bevacizumab analogs, against continuous drug therapy

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：

卫旭彪 

研究负责人：

程树群 

Applicant：

Xubiao Wei 

Study leader：

Shuqun Cheng 

申请注册联系人电话：

Applicant telephone：

 +86 136 3635 4249

研究负责人电话：

Study leader's
telephone：

+86 21 8187 5251

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：

 weixubiao@hotmail.com

研究负责人电子邮件：

Study leader's E-mail：

 chengshuqun@aliyun.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：

上海市杨浦区长海路225号

研究负责人通讯地址：

上海市杨浦区长海路225号

Applicant address：

225 Changhai Road, Yangpu District, Shanghai, China

Study leader's address：

225 Changhai Road, Yangpu District, Shanghai, China

申请注册联系人邮政编码：

Applicant postcode：

 200438

研究负责人邮政编码：

Study leader's postcode：

 200438

申请人所在单位：

海军军医大学第三附属医院/东方肝胆外科医院

Applicant's institution：

Eastern Hepatobiliary Surgery Hospital

研究负责人所在单位：

海军军医大学第三附属医院/东方肝胆外科医院

Affiliation of the Leader：

Eastern Hepatobiliary Surgery Hospital

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：

 EHBHKY2023-H015-P001

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：

海军军医大学第三附属医院伦理学委员会

Name of the ethic committee：

Ethics Committee of the Third affliated Hospital of Navy Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-06-05 00:00:00

伦理委员会联系人：

邰小云

Contact Name of the ethic committee：

Xiaoyun Tai

伦理委员会联系地址：

上海市杨浦区长海路225号

Contact Address of the ethic committee：

225 Changhai Road, Yangpu District, Shanghai, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 152 2139 0719

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：

东方肝胆外科医院

Primary sponsor：

Eastern Hepatobiliary Surgery Hospital

研究实施负责（组长）单位地址：

上海市杨浦区长海路225号

Primary sponsor's address：

225 Changhai Road, Yangpu District, Shanghai, 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)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

东方肝胆外科医院

具体地址：

上海市杨浦区长海路225号

Institution
hospital：

Eastern Hepatobiliary Surgery Hospital

Address：

225 Changhai Road, Yangpu District, Shanghai, China

经费或物资来源：

科技部重点研发计划；国家自然科学基金

Source(s) of funding：

the National Key R&D Program of China (No: 2022YFC2503700, 2022YFC2503705); the National Natural Science Foundation of China (No: 82102941; 82103483)

研究疾病：

肝细胞癌  

Target disease：

Hepatocellular carcinoma

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：

随机平行对照 

Study design：

Parallel 

研究目的：

通过随机对照研究，根据治疗失败时间（TTF）、总体生存期（OS）、安全性等指标来评价BCLC B/C期肝细胞癌行经肝动脉栓塞化疗（TACE）联合信迪利单抗和贝伐珠单抗类似物治疗降为BCLC A期后行手术切除或射频消融对比持续药物治疗的有效性和安全性。  

Objectives of Study：

Through a methodically designed randomized controlled trial, to compare the efficacy and safety of surgical resection or radiofrequency ablation versus the continuation of drug therapy with sintilimab and Bevacizumab analogs in hepatocellular carcinoma patients. These patients have been down-staged to BCLC stage A from BCLC stages B/C following treatment with Transarterial Chemoembolization (TACE) in combination with the aforementioned drugs. The primary endpoints for assessment in this clinical trial include Time to Treatment Failure (TTF), Overall Survival (OS), and a comprehensive safety profile.

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. 患者自愿加入本研究，签署知情同意书； 2. 年龄在20岁至75岁之间，性别不限； 3. 临床诊断或经病理诊断的中晚期肝细胞癌(BCLC-B/C)，且经过TACE联合双达方案治疗后降为BCLC A期（RECIST 1.1评估）； 4. 肝脏功能Child pugh 评分 <= 7分，ALBI 分级 1-2级； 5. ECOG评分：0-1分； 6. 预期生存期≥12周； 7. 重要器官功能复合下列要求（评估前14天内不能使用任何血液成分（如白蛋白）、细胞生长因子及其他纠正治疗的药物）： （1）血红蛋白≥90g/L； （2）中性粒细胞计数≥1.5×109/L； （3）血小板计数≥60×109/L； （4）血清白蛋白数≥30g/L； （5）总胆红素≤1.5*ULN； （6）ALT和AST≤3*ULN； （7）AKP≤2.5*ULN； （8）血清肌酐≤1.5*ULN； 8. 乙肝感染状态：HBV-DNA<2000 copies/ml；或患者 HBV-DNA>2000 copies/ml，则开始前至少提前1周开始口服抗病毒药物； 9. 非手术绝育或育龄期女性患者，需要在研究治疗期间和治疗结束后3个月内采用一种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套）；非手术绝育的育龄期女性患者在研究入组前的72小时内血清或尿HCG检查必须为阴性；而且必须为非哺乳期。

Inclusion criteria

1. Patients voluntarily join this study and sign an informed consent form; 2. Age is between 20 and 75 years old, with no gender restriction; 3. Clinically diagnosed or pathologically confirmed intermediate or advanced hepatocellular carcinoma (BCLC-B/C), which has been downgraded to BCLC stage A (according to RECIST 1.1 criteria) after treatment with TACE in combination with the dual drugs; 4. Liver function Child-Pugh score <= 7 points, ALBI grade 1-2; 5. ECOG score: 0-1 point; 6. Expected survival period >=12 weeks; 7. Important organ functions meet the following requirements (no use of any blood components (such as albumin), cell growth factors, and other corrective therapeutic drugs within 14 days prior to evaluation): (1) Hemoglobin >= 90g/L; (2) Neutrophil count >= 1.5×109/L; (3) Platelet count >= 60×109/L; (4) Serum albumin >= 30g/L; (5) Total bilirubin <= 1.5ULN; (6) ALT and AST <= 3ULN; (7) AKP <= 2.5ULN; (8) Serum creatinine <= 1.5ULN; 8. Hepatitis B infection status: HBV-DNA < 2000 copies/mL; or if the patient's HBV-DNA > 2000 copies/mL, start taking oral antiviral drugs at least one week in advance; 9. For non-surgically sterilized or women of childbearing age, they need to use a medically approved contraceptive measure (such as an intrauterine device, contraceptive pills, or condoms) during the research treatment and within three months after the end of the treatment. For non-surgically sterilized women of childbearing age, a serum or urine HCG test must be negative within 72 hours before joining the study; moreover, they must not be breastfeeding.

排除标准：

1. 既往使用过除双达方案外其他靶向、免疫或化疗药物；接受过针对肝癌的射频、手术或放疗等局部治疗； 2.有临床症状的腹水，需要穿刺、持续引流或既往3个月接受过腹水引流者，仅有影像学显示少量腹水但不伴有临床症状者除外； 3. 有未能良好控制的心脏临床症状或疾病，如： （1）2级以上的心力衰竭，不稳定型心绞痛； （2）1年内发生过心肌梗死； （3）有临床意义的室上性或室性心律失常需要治疗或干预； （4）严重的甲状腺亢进或者甲减患者； 4. 凝血功能异常（INR>2.0，PT>16s），具有出血倾向或正在接受溶栓或抗凝治疗，允许预防性使用小剂量阿司匹林、低分子肝素等； 5. 随机前3个月内出现过显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、有出血危险的食管胃底静脉曲张、出血性胃溃疡或患有脉管炎等，基线期若大便隐血阳性需复查，若仍未转阴需要进行胃镜和肠镜检查，若胃镜提示重度食管胃底静脉曲张伴红色征则不能入组； 6. 已知存在的遗传性或获得性出血及血栓倾向（如血友病患者、凝血机能障碍、血小板减少等）； 7. 尿常规提示尿蛋白≥++并经证实24小时尿蛋白量>1.0g； 8. 先前接受过激素治疗，在治疗完成后（末次用药），研究用药前不足4周的患者；先前治疗引起的不良事件（脱发除外）未恢复至≤CTCAE 1级的患者； 9. 患者有活动性感染，用药前7天内有不明原因发热≥38.5℃、或基线期白细胞计数≥15*10^9/L； 10. HCV、HIV或梅毒感染； 11. 患者既往3年内或同时患者其它恶性肿瘤； 12. 长期患有头痛或偏头痛，服药不能缓解的患者； 13. 研究者认为其他原因不宜参加本试验者如合并严重精神疾病、药物滥用、家庭或社会因素不宜入组等。

Exclusion criteria：

1. Previous use of other targeted, immune or chemotherapy drugs other than the dual approach; previous local treatment for liver cancer such as radiofrequency, surgery, or radiotherapy; 2. Patients with clinically symptomatic ascites that require puncture, continuous drainage, or those who have received ascites drainage in the past three months, except those who only have a small amount of ascites shown by imaging but are without clinical symptoms; 3. Patients with uncontrolled clinical symptoms or diseases of the heart, such as: (1) Heart failure of more than grade 2, unstable angina; (2) Myocardial infarction in the past year; (3) Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; (4) Severe hyperthyroidism or hypothyroidism patients. 4. Abnormal coagulation function (INR>2.0, PT>16s), bleeding tendency or currently receiving thrombolysis or anticoagulant treatment, preventive use of low-dose aspirin, low-molecular-weight heparin, etc., is allowed; 5. Significant clinically significant bleeding symptoms in the past three months before randomization or a clear tendency to bleed, such as gastrointestinal bleeding, esophageal varices with a risk of bleeding, bleeding gastric ulcers or patients with vasculitis, etc. If there is positive occult blood in the stool at baseline, re-examination is needed, and if it does not turn negative, gastroscopy and colonoscopy are needed. If gastroscopy indicates severe esophagogastric varices with red signs, the patient cannot be enrolled; 6. Known hereditary or acquired bleeding and thrombotic tendency (such as hemophilia, coagulation dysfunction, thrombocytopenia, etc.); 7. Urinalysis suggests urine protein >= ++ and 24-hour urine protein >1.0g is confirmed; 8. Patients who have previously received hormone therapy and it is less than four weeks before the use of research drugs after the treatment is completed (last dose); patients whose adverse events caused by previous treatment (except hair loss) have not recovered to <= CTCAE grade 1; 9. Patients with active infection, unexplained fever >= 38.5°C within 7 days before drug use, or a white blood cell count >= 15*10^9/L at baseline; 10. HCV, HIV or syphilis infection; 11. Patients with other malignant tumors within the past three years or at the same time; 12. Patients who have long suffered from headaches or migraines and cannot be relieved by medication; 13. Patients who, for other reasons considered by the researchers, should not participate in this trial, such as severe mental illness, drug abuse, family or social factors unsuitable for enrollment, etc.

研究实施时间：

Study execute time：

从 From 2023-07-24 00:00:00至 To 2028-08-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-08-01 00:00:00 至 To 2028-06-30 00:00:00

干预措施：

Interventions：

组别：

降期后手术/消融组

样本量：

 40

Group：

Surgery/RFA

Sample size：

干预措施：

双达停药6周（期间使用一次达攸同）后行肝癌根治性切除或射频消融术，术后4周开始辅助使用双达治疗；常规随访。

干预措施代码：

Intervention：

After discontinuing the dual drugs for 6 weeks (with one dose of Bevacizumab analogs administered during this period), radical resection or radiofrequency ablation of hepatocellular carcinoma is performed. Four weeks after the surgery, adjuvant treatment with the dual approach is started; regular follow-up is performed.

Intervention code：

组别：

持续药物治疗组

样本量：

 40

Group：

Continuous drug treatment.

Sample size：

干预措施：

持续双达方案（信迪利单抗 200mg+贝伐珠单抗类似物 15mg/kg， 静脉滴注， 3周一次）治疗；常规随访。

干预措施代码：

Intervention：

Continuous treatment with the dual drugs (Sintilimab 200mg + Bevacizumab analog 15mg/kg, administered via intravenous infusion, once every 3 weeks); regular follow-up is performed.

Intervention code：

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)：

 东方肝胆外科医院 

单位级别：

 三甲 

Institution
hospital：

Eastern Hepatobiliary Surgery Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

治疗失败时间

指标类型：

主要指标

Outcome：

time to reatment failure

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总体生存时间

指标类型：

次要指标

Outcome：

Overall survival, 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：

毒副作用

指标类型：

主要指标

Outcome：

adverse events

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：

肿瘤组织

组织：

肝脏

Sample Name：

tumor tissue

Tissue：

liver

人体标本去向

 使用后销毁  

说明

保存3年

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 20 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）：

简单随机：电脑产生随机号码。

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

A computer-generated randomization code.

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：

无

Blinding：

none

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）：

本研究的临床数据并未公开。然而，在得到机构伦理委员会批准并提出合理的请求后，可以从通讯作者（程树群：chengshuqun@aliyun.com）处获取这些数据，这些数据将在论文发表后保留三年。

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

Clinical data in this study are not publicly available. The data are, however, for 3 years, available from the corresponding author (Shuqun Cheng: chengshuqun@aliyun.com), upon reasonable request and with the approval of the institutional ethical committees.

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：

病历记录表

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

CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2023-07-24 17:02:28