ChiCTR2500106235 版本V1.0 版本创建时间2025/07/21 10:55:00 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：

ChiCTR2500106235 

最近更新日期：

Date of Last Refreshed on：

2025-07-21 10:54:55 

注册时间：

Date of Registration：

2025-07-21 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

多纳非尼与替雷利珠单抗联合经肝动脉灌注化疗（HAIC）一线治疗BCLC B/C期肝细胞癌有效性和安全性的前瞻性、单臂临床研究

Public title：

A prospective, single-arm clinical study on the efficacy and safety of Donafenib combined with Tislelizumab and hepatic arterial infusion chemotherapy (HAIC) as first-line treatment for BCLC stage B/C hepatocellular carcinoma.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

多纳非尼与替雷利珠单抗联合经肝动脉灌注化疗（HAIC）一线治疗BCLC B/C期肝细胞癌有效性和安全性的前瞻性、单臂临床研究

Scientific title：

A prospective, single-arm clinical study on the efficacy and safety of Donafenib combined with Tislelizumab and hepatic arterial infusion chemotherapy (HAIC) as first-line treatment for BCLC stage B/C hepatocellular carcinoma.

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：

李万祯 

研究负责人：

李万祯 

Applicant：

Wanzhen Li 

Study leader：

Wanzhen Li 

申请注册联系人电话：

Applicant telephone：

+86 183 4427 2588

研究负责人电话：

Study leader's telephone：

+86 183 4427 2588

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：

646477988@qq.com

研究负责人电子邮件：

Study leader's E-mail：

646477988@qq.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：

广东省茂名市茂南区为民路101号

研究负责人通讯地址：

广东省茂名市茂南区为民路101号

Applicant address：

No. 101, Weimin Road, Maonan District, Maoming, Guangdong

Study leader's address：

No. 101, Weimin Road, Maonan District, Maoming, Guangdong

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：

茂名市人民医院

Applicant's institution：

Maoming People's Hospital

研究负责人所在单位：

茂名市人民医院

Affiliation of the Leader：

Maoming People's Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

PJ2023MI-K104-02

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：

茂名市人民医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Maoming People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2024-08-30 00:00:00

伦理委员会联系人：

王广文

Contact Name of the ethic committee：

Guangwen Wang

伦理委员会联系地址：

广东省茂名市茂南区为民路101号

Contact Address of the ethic committee：

No. 101, Weimin Road, Maonan District, Maoming, Guangdong

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 159 1528 0880

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：

茂名市人民医院

Primary sponsor：

Maoming People's Hospital

研究实施负责（组长）单位地址：

广东省茂名市茂南区为民路101号

Primary sponsor's address：

No. 101, Weimin Road, Maonan District, Maoming, Guangdong

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)：

茂名

Country：

China

Province：

Guangdong

City：

Maoming

单位(医院)：

茂名市人民医院

具体地址：

广东省茂名市茂南区为民路101号

Institution
hospital：

Maoming People's Hospital

Address：

No. 101, Weimin Road, Maonan District, Maoming, Guangdong

经费或物资来源：

自筹

Source(s) of funding：

Self-financing

Target disease：

Hepatocellular carcinoma

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

单臂 

Study design：

Single arm 

研究目的：

探索多纳非尼与替雷利珠单抗联合肝动脉灌注化疗（HAIC）一线治疗BCLC B/C期肝细胞癌患者的有效性和安全性。  

Objectives of Study：

Explore the efficacy and safety of Donafenib combined with Tislelizumab and hepatic arterial infusion chemotherapy (HAIC) as first-line treatment for patients with BCLC stage B/C hepatocellular carcinoma.

药物成份或治疗方案详述：

（1）多纳非尼 多纳非尼给药窗口期为首次 HAIC 前后 7 天内。患者每天固定时间口服多纳非尼，每日 2 次，每次 2 片（0.1g/片），用药至PD。治疗期间，结合受试者给药安全耐受性，根据药品说明书进行调整。 （2）替雷利珠单抗 替雷利珠单抗静脉注射给药，固定剂量200mg，静脉滴注给药，首次输注60min，如耐受可，以后每次输注30min，3周给药1次，每3周为1个周期，累计最长用药期为2年。 研究期间，替雷利珠每3周给药1次，给药窗口期为HAIC治疗后7天内。 （3）肝动脉灌注化疗（HAIC） 在DSA引导下经皮股动脉插管成功后实施腹腔干及肠系膜上动脉造影，必要时行膈动脉造影，明确肿瘤的供血动脉。最终将动脉留置微导管管头超选停留在肿瘤供血动脉后，固定包扎留置导管送患者回病房。在病房将导管接注射泵持续泵入如下化疗药： ?奥沙利铂 85mg/m2，2~3小时，Day 1； ?亚叶酸钙 200mg/m^2，2小时，Day1； ?5-FU 2500mg/m^2，48小时。 拔除导管，加压包扎止血12小时。 上述HAIC治疗过程每3周重复，4-6次，不超过6次。 

Description for medicine or protocol of treatment in detail：

(1) Donafenib The dosing window for donafenib is within 7 days before and after the first HAIC. Patients take donafenib orally at a fixed time every day, twice a day, 2 tablets each time (0.1 g/tablet), until progressive disease (PD). During the treatment period, adjust according to the safety and tolerability of the subject's administration and in accordance with the drug instructions. (2) Tislelizumab Tislelizumab is administered intravenously at a fixed dose of 200 mg. It is administered as an intravenous drip. The first infusion lasts for 60 minutes. If tolerated, subsequent infusions can last for 30 minutes each time. It is administered once every 3 weeks, with each 3-week period considered one cycle. The cumulative maximum treatment period is 2 years. During the study period, tislelizumab is administered once every 3 weeks, with the dosing window being within 7 days after HAIC treatment. (3) Hepatic arterial infusion chemotherapy (HAIC) After successful percutaneous femoral artery catheterization under the guidance of digital subtraction angiography (DSA), celiac trunk and superior mesenteric artery angiography is performed. If necessary, phrenic artery angiography is carried out to clarify the tumor's blood supply arteries. Finally, after the tip of the arterial indwelling microcatheter is selectively placed in the tumor blood supply artery, the catheter is fixed and dressed, and the patient is sent back to the ward with the catheter in place. In the ward, the catheter is connected to an injection pump to continuously infuse the following chemotherapy drugs: - Oxaliplatin: 85 mg/m2, over 2 - 3 hours, on Day 1; - Leucovorin calcium: 200 mg/m2, over 2 hours, on Day 1; - 5-Fluorouracil (5-FU): 2500 mg/m2, over 48 hours. The catheter is then removed, and the puncture site is compressed and bandaged to stop bleeding for 12 hours. The above HAIC treatment process is repeated every 3 weeks, for 4 - 6 times, not exceeding 6 times. 

纳入标准：

患者必须满足以下所有入选标准才可入组本研究： 1. 患者自愿加入本研究，签署知情同意书； 2. 年龄>=18 岁，<=75 岁，男女皆可； 3. 临床或病理学确诊的BCLC B期或C期肝细胞癌，既往未接受过任何肝癌系统治疗； 4. 至少有一个肝内可评价病灶，肝内病灶是主要的肿瘤负荷。（根据 RECIST v1.1 要求，该可测量病灶螺旋 CT 扫描长径>= 10 mm 或肿大淋巴结短径>=15 mm）； 5. Child-Pugh 评分<=7 分（Child-Pugh A-B）； 6. ECOG 评分：0～2； 7. 预期生存期>=12 周； 8. 主要器官功能符合下列要求（首次用药前 14 天内不允许使用任何血液成分、细胞生长因子及其他纠正治疗的药物）： 1)血常规检查须符合以下标准： A.中性粒细胞绝对计数（ANC）>=3×10^9/L； B.血小板（PLT）>=80×10^9/L； C.血红蛋白>=90g/L; 2)血生化检查须符合以下要求： A.血清白蛋白（ALB）>=28g/L； B.谷草转氨酶（AST）<=3×ULN； C.谷丙转氨酶（ALT）<=3×ULN； D.碱性磷酸酶（ALP）<=2.5×ULN； E.总胆红素（TBil）<=1.5×ULN； F.血清肌酐（Cr）<=1.5×ULN 3)促甲状腺激素（TSH）<=1×ULN（如异常应同时考察 FT3、FT4 水平，如 FT3 及 FT4水平正常，可以入组） 4)国际标准化比率（INR）<=2.3或凝血酶原时间（PT）超过正常对照的范围<=6秒，要求未进行抗凝治疗。

Inclusion criteria

Patients must meet all of the following inclusion criteria to be enrolled in this study: 1.Patients voluntarily join this study and sign the informed consent form. 2.Aged 18 years >=and <=75 years, either male or female. 3.Clinically or pathologically diagnosed with BCLC stage B or C hepatocellular carcinoma, and have not received any prior systemic treatment for liver cancer. 4.At least one intrahepatic evaluable lesion. The intrahepatic lesion is the main tumor burden. (According to RECIST v1.1 requirements, the long diameter of the measurable lesion on spiral CT scan should be >=10 mm or the short diameter of enlarged lymph nodes should be >=5 mm.) 5.Child-Pugh score <=7 points (Child-Pugh A - B). 6.ECOG score: 0 - 2. 7.Expected survival time >=12 weeks. 8.The main organ functions meet the following requirements (no blood components, cell growth factors or other corrective treatment drugs are allowed within 14 days before the first medication use): (1)Blood routine examination must meet the following criteria: A. Absolute neutrophil count (ANC) >=3×10?/L; B. Platelet (PLT) >=80×10?/L; C. Hemoglobin >=90 g/L; (2)Blood biochemical examination must meet the following requirements: A. Serum albumin (ALB) >=28 g/L; B. Aspartate aminotransferase (AST) <=3×ULN; C. Alanine aminotransferase (ALT) <=3×ULN; D. Alkaline phosphatase (ALP) <=2.5×ULN; E. Total bilirubin (TBil) <=1.5×ULN; F. Serum creatinine (Cr) <=1.5×ULN; (3)Thyroid-stimulating hormone (TSH) <=1×ULN (if abnormal, FT3 and FT4 levels should also be examined simultaneously. If FT3 and FT4 levels are normal, the patient can be enrolled). (4)International normalized ratio (INR) <=2.3 or prothrombin time (PT) exceeds the normal control range by <=6 seconds, and anticoagulation therapy has not been carried out.

排除标准：

符合以下条件中任何一条，须排除出本研究： 1. 接受过肝脏局部治疗 HCC； 2. 患者存在任何活动性自身免疫病或有自身免疫病病史； 3. 患者正在使用免疫抑制剂、或全身激素治疗以达到免疫抑制目的，并在入组前 2 周内仍在继续使用的； 4. 目前伴有间质性肺炎或间质性肺病，或既往有需激素治疗的间质性肺炎或间质性肺病病史者；活动性结核； 5. 对其他单克隆抗体发生过重度过敏反应； 6. 已知有中枢神经系统转移或肝性脑病病史者； 7. 有器官移植史者； 8. 肝内肿瘤病灶呈弥漫性改变； 9. 经规律降压治疗血压仍无法降至正常范围者（收缩压＞140mmHg，舒张压＞90mmHg）。 10. >=II级的冠心病、心律失常（包括QTc间期延长男性＞450ms，女性＞470ms）。 11. 症状性充血性心力衰竭（纽约心脏病协会分级II-IV级）或症状性或控制不佳的心律失常； 12. 凝血功能异常（INR＞1.5ULN、APTT＞1.5ULN），并具有出血倾向； 13. 入组前6个月内发生的动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作、脑出血、脑梗塞）、深静脉血栓及肺栓塞等； 14. 尿常规提示尿蛋白>=++并经证实 24 小时尿蛋白量>1.0g； 15. 需要治疗的活动性感染或首次给药前7天内使用过全身性抗感染药物； 16. 患者先天或后天免疫功能缺陷（如 HIV 感染者）； 17. 合并乙肝及丙肝共同感染； 18. 患者既往 3 年内或同时患有其它恶性肿瘤（已治愈的皮肤基底细胞癌和宫颈原位癌除外）； 19. 怀孕或哺乳期妇女，或不愿采取避孕措施的育龄妇女； 20. 经研究者判断，患者有其他可能影响研究结果或导致本研究被迫中途终止的因素，如酗酒、药物滥用、其他的严重疾病（含精神疾病）需要合并治疗，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到患者的安全。

Exclusion criteria：

Patients meeting any of the following conditions must be excluded from this study: 1. Have received local liver treatment for HCC. 2. Patients with any active autoimmune disease or a history of autoimmune disease. 3. Patients who are currently using immunosuppressants or systemic hormone therapy for immunosuppressive purposes and are still continuing to use them within 2 weeks before enrollment. 4. Currently suffering from interstitial pneumonia or interstitial lung disease, or having a history of interstitial pneumonia or interstitial lung disease that required steroid treatment in the past; active tuberculosis. 5. Have had a severe allergic reaction to other monoclonal antibodies. 6. Known history of central nervous system metastasis or hepatic encephalopathy. 7. Have a history of organ transplantation. 8. Diffuse changes in intrahepatic tumor lesions. 9. Blood pressure cannot be reduced to the normal range despite regular antihypertensive treatment (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg). 10. Coronary heart disease or arrhythmia of grade >= II (including QTc interval prolongation: > 450 ms in males, > 470 ms in females). 11. Symptomatic congestive heart failure (New York Heart Association Class II - IV) or symptomatic or poorly controlled arrhythmia. 12. Coagulation dysfunction (INR > 1.5 ULN, APTT > 1.5 ULN) with a tendency to bleed. 13. Arterial/venous thrombotic events within 6 months before enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism. 14. Urine routine shows urine protein >= ++ and 24-hour urine protein is confirmed to be > 1.0 g. 15. Active infection requiring treatment or use of systemic anti-infective drugs within 7 days before the first dose. 16. Patients with congenital or acquired immune deficiency (such as HIV-infected individuals). 17. Coinfection with hepatitis B and hepatitis C. 18. Patients who have had other malignancies within the past 3 years or at the same time (except for cured basal cell carcinoma of the skin and cervical carcinoma in situ). 19. Pregnant or breastfeeding women, or women of childbearing age who are unwilling to take contraceptive measures. 20. In the opinion of the investigator, the patient has other factors that may affect the study results or lead to the premature termination of this study, such as alcohol abuse, drug abuse, other serious diseases (including mental illnesses) requiring combination therapy, significant laboratory abnormalities, accompanied by family or social factors that may affect the patient's safety.

研究实施时间：

Study execute time：

从 From 2023-06-01 00:00:00至 To 2026-05-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-10-09 00:00:00 至 To 2026-05-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

56

Group：

Experimental group

Sample size：

干预措施：

多纳非尼、替雷利珠单抗联合肝动脉灌注化疗（HAIC）

干预措施代码：

Intervention：

Donafenib, Tislelizumab combined with hepatic arterial infusion chemotherapy (HAIC).

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广东 

市(区县)：

 茂名 

Country：

China 

Province：

Guangdong 

City：

Maoming 

单位(医院)：

茂名市人民医院 

单位级别：

三甲 

Institution
hospital：

Maoming People's Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存时间

指标类型：

主要指标

Outcome：

Progression-Free Survival (PFS)

Type：

Primary indicator

测量时间点：

指从随机至首次出现疾病进展（RECIST1.1标准）或死亡（以先发生者为准）之间的时间。

测量方法：

从随机开始至48周内，每6周进行一次影像学评估；之后每12周进行一次影像学评估；如怀疑新发病灶可实时检查；首次评价PR/CR受试者须在4周后进行疗效确认。

Measure time point of outcome：

It refers to the time from randomization to the first occurrence of disease progression (according.

Measure method：

From randomization, imaging assessments are conducted every 6 weeks within 48 weeks; thereafter, imaging assessments are performed every 12 weeks. If new lesions are suspected, real-time examinations can be carried out. For subjects initially evaluated as PR/CR, efficacy confirmation must be performed 4 weeks later.

指标中文名：

总生存期(OS)

指标类型：

次要指标

Outcome：

Overall Survival

Type：

Secondary indicator

测量时间点：

指从随机化开始至因任何原因引起死亡的时间。这里的随机化开始时间对于临床试验来说很关键，它是一个明确界定的起始点。

测量方法：

研究治疗终止后，定期通过中心访视或者电话随访收集患者生存状态，直至死 亡；若受试者在试验过程中死亡，则记录实际死亡时间。

Measure time point of outcome：

It refers to the time from the start of randomization to death due to any cause.

Measure method：

After the termination of the study treatment, the patient's survival status will be collected regularly through center visits or telephone follow-ups until death; if the subject dies during the trial, the actual time of death will be recorded.

指标中文名：

至疾病进展时间（TTP）

指标类型：

次要指标

Outcome：

Time to Progression

Type：

Secondary indicator

测量时间点：

从随机分组开始到肿瘤客观进展的时间。

测量方法：

起始点为随机分组时间或者开始治疗的时间（根据具体研究设计而定）。终点为根据疗效评价标准确定的肿瘤进展时间。

Measure time point of outcome：

Time from randomization to objective tumor progression.

Measure method：

The starting point is the time of randomization or the initiation of treatment (depending on the specific study design). The endpoint is the time to tumor progression determined based on the efficacy evaluation criteria.

指标中文名：

至缓解时间（TTR）

指标类型：

次要指标

Outcome：

Time to Response

Type：

Secondary indicator

测量时间点：

从开始治疗到首次观察到肿瘤客观缓解所经历的时间.

测量方法：

起始点为首次达到客观缓解（CR或PR）的时间，这个时间需要根据严格的疗效评价标准（如RECIST标准）通过影像学检查或其他评估手段来确定。

Measure time point of outcome：

Time from treatment initiation to first observation of objective tumor response.

Measure method：

The starting point is defined as the time of first achieving objective tumor response (complete response [CR] or partial response [PR]), which must be determined based on strict efficacy evaluation criteria (such as RECIST criteria) through imaging assessments or other validated evaluation methods.?

指标中文名：

客观缓解率(ORR)

指标类型：

次要指标

Outcome：

Objective Response Rate

Type：

Secondary indicator

测量时间点：

Tumor shrinkage reaches a certain magnitude and is maintained for a specified duration.

测量方法：

肿瘤缩小达到一定量并且保持一定时间的病人的比例，包括完全缓解（CR）和部分缓解（PR）

Measure time point of outcome：

Tumor shrinkage reaches a certain magnitude and is maintained for a specified duration.

Measure method：

Proportion of patients achieving tumor shrinkage of a specified magnitude that is maintained for a defined duration, including both complete response (CR) and partial response (PR).

指标中文名：

疾病控制率(DCR)

指标类型：

次要指标

Outcome：

Disease Control Rate

Type：

Secondary indicator

测量时间点：

肿瘤缩小或稳定且维持一定时间。

测量方法：

肿瘤缩小或稳定且维持一定时间的病人比例，包括CR、PR和SD。

Measure time point of outcome：

Tumor shrinkage or stable disease maintained for a specified duration.

Measure method：

Proportion of patients achieving tumor shrinkage, stable disease (SD), or better (including complete response [CR] and partial response [PR]) that is maintained for a specified duration.?

指标中文名：

缓解持续时间(DOR)

指标类型：

次要指标

Outcome：

Duration of Response

Type：

Secondary indicator

测量时间点：

从首次观察到肿瘤客观缓解到肿瘤再次进展或患者死亡的时间。

测量方法：

从首次观察到肿瘤客观缓解（包括完全缓解CR和部分缓解PR）到肿瘤再次进展（根据预先设定的疗效评价标准，如RECIST标准）或患者死亡的时间。

Measure time point of outcome：

Time from first documentation of objective tumor response to tumor progression or patient death.

Measure method：

Time from first documentation of objective tumor response (including complete response [CR] and partial response [PR]) to tumor progression (as determined by predefined efficacy evaluation criteria such as RECIST criteria) or patient death.?

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

Sample Name：

None

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

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 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）：

无

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：

无

Blinding：

None.

是否共享原始数据：

IPD sharing

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）：

在试验结束6个月内上传试验数据。http://www.medresman.org.cn/login.aspx。

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

Upload the trial data within 6 months after the completion of the trial.http://www.medresman.org.cn/login.aspx

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：

病例报告表

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

Case Report Form

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-07-21 10:54:55