ChiCTR2400090801 版本V1.0 版本创建时间2024/10/14 09:01:42 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：

 ChiCTR2400090801 

最近更新日期：

Date of Last Refreshed on：

 2024-10-14 09:01:34 

注册时间：

Date of Registration：

 2024-10-14 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

经肝动脉化疗栓塞术（TACE）联合阿得贝利单抗和甲磺酸仑伐替尼用于不可切除的晚期肝细胞癌的开放、单中心、前瞻性研究

Public title：

An open-label, single-center, prospective study of transarterial chemoembolization (TACE) combined with Adabelimab and lenvatinib mesylate for unresectable advanced hepatocellular carcinoma.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

经肝动脉化疗栓塞术（TACE）联合阿得贝利单抗和甲磺酸仑伐替尼用于不可切除的晚期肝细胞癌的开放、单中心、前瞻性研究

Scientific title：

An open-label, single-center, prospective study of transarterial chemoembolization (TACE) combined with Adabelimab and lenvatinib mesylate for unresectable advanced 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：

孙善波 

研究负责人：

周卫忠 

Applicant：

Shanbo Sun 

Study leader：

Weizhong Zhou 

申请注册联系人电话：

Applicant telephone：

 +86 156 5107 6004

研究负责人电话：

Study leader's
telephone：

+86 25 8371 8836

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：

 sunshanbo123@163.com

研究负责人电子邮件：

Study leader's E-mail：

 xmjbq007@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：

江苏省南京市鼓楼区中央路19号

研究负责人通讯地址：

江苏省南京市鼓楼区广州路300号

Applicant address：

19 Zhongfang Road, Gulou District, Nanjing City, Jiangsu Province, China

Study leader's address：

300 Guangzhou Road, Gulou District, Nanjing City, Jiangsu Province, 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：

江苏恒瑞医药科技股份有限公司

Applicant's institution：

Jiangsu Hengrui Medical Technology Co., LTD

研究负责人所在单位：

南京医科大学第一附属医院(江苏省人民医院)

Affiliation of the Leader：

The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province 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：

 2024-SR-331

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：

南京医科大学第一附属医院伦理委员会

Name of the ethic committee：

Ethics Committee of the First Affiliated Hospital of Nanjing Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-05-08 00:00:00

伦理委员会联系人：

赵俊

Contact Name of the ethic committee：

Jun Zhao

伦理委员会联系地址：

江苏省南京市鼓楼区广州路300号

Contact Address of the ethic committee：

300 Guangzhou Road, Gulou District, Nanjing City, Jiangsu Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 25 6830 6360

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：

南京医科大学第一附属医院(江苏省人民医院)

Primary sponsor：

The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital)

研究实施负责（组长）单位地址：

江苏省南京市鼓楼区广州路300号

Primary sponsor's address：

300 Guangzhou Road, Gulou District, Nanjing City, Jiangsu Province, 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)：

江苏

市(区县)：

Country：

China

Province：

jiangsu

City：

单位(医院)：

南京医科大学第一附属医院

具体地址：

江苏省南京市鼓楼区广州路300号

Institution
hospital：

The First Affiliated Hospital of Nanjing Medical University

Address：

300 Guangzhou Road, Gulou District, Nanjing City, Jiangsu Province, China

经费或物资来源：

自募

Source(s) of funding：

Self recruitment

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：

单臂 

Study design：

Single arm 

研究目的：

? 评价TACE联合阿得贝利单抗和甲磺酸仑伐替尼用于不可切除的晚期肝细胞癌的有效性和安全性  

Objectives of Study：

Evaluate the efficacy and safety of TACE combined with Adabelimab and lenvatinib mesylate for unresectable advanced hepatocellular carcinoma.

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. 自愿参加本研究，签署知情同意书； 2. 年龄 ≥18 周岁，男女不限； 3. 经病理组织学、细胞学或影像学确诊的肝细胞癌； 4. CNLC IIb/IIIa/ IIIb 期或BCLC分期 B/C 期肝细胞癌受试者； 5. 既往未接受过针对肝细胞癌的系统治疗，或既往仅接受过一线针对肝细胞癌的系统治疗/手术切除，出现PD/SD且与第一次给药间隔时长 ≥4周； 6. 既往未接受TACE治疗，或接受TACE但间隔市时长 ≥4周的患者（TACE抵抗患者除外）； 7. Child-Pugh 肝功能评级：A~B 级（≤ 9 分）； 8. ECOG PS 评分：0~1 分； 9. 若患有乙型肝炎病毒（HBV）感染，如 HBsAg 阳性，需检测 HBV-DNA，且HBV-DNA 需 <2000 IU/mL（若研究中心只有 copy/mL 检测单位，则必须 <104 copy/mL）；对于 HBV-DNA≥2000 IU/mL 的受试者，入组前接受至少 1 周的抗病毒治疗（仅允许使用核苷类药物如恩替卡韦、富马酸替诺福韦酯和富马酸丙酚替诺福韦片），且病毒拷贝数相比治疗前下降 10 倍（1 lg）以上。对于 HBV 感染者，需在研究期间全程接受抗病毒治疗。丙型肝炎病毒（HCV）-RNA 阳性受试者必须按治疗指南接受抗病毒治疗； 11. 育龄妇女在开始首次用药前必须妊娠检测为（βHCG）阴性。育龄妇女和男子(与育龄妇女发生性关系)必须同意在治疗期间和末次给药 6 个月内避孕。

Inclusion criteria

Voluntarily participate in this study and sign an informed consent form; Age ≥18 years old, no gender restrictions; Hepatocellular carcinoma diagnosed by pathological histology, cytology, or imaging; Subjects with CNLC stage IIb/IIIa/IIIb or BCLC stage B/C hepatocellular carcinoma; No prior systemic treatment for hepatocellular carcinoma, or only one line of systemic treatment/surgical resection for hepatocellular carcinoma in the past, with PD/SD and a gap of ≥4 weeks from the first administration; No prior TACE treatment, or patients who have received TACE with a gap of ≥4 weeks (except for TACE-resistant patients); Child-Pugh liver function rating: A~B grade (≤ 9 points); ECOG PS score: 0~1 points; Women of childbearing age must have a negative pregnancy test (βHCG) before the first dose. Women of childbearing age and men (who have sexual relations with women of childbearing age) must agree to use contraception during the treatment period and within 6 months after the last administration.

排除标准：

1. 已知肝内胆管细胞癌、肉瘤样肝细胞癌、混合细胞癌（ICC 成分超过 30%）及纤维板层细胞癌；5 年内或同时患有除 HCC 之外的其它活动性恶性肿瘤；入组前经研究者评估需行手术联合射频消融治疗者。已治愈的局限性肿瘤，如皮肤基底细胞癌、皮肤鳞癌、浅表性膀胱癌、前列腺原位癌、宫颈原位癌、乳腺原位癌等可以入组； 2. 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，或其他可能干扰免疫相关肺毒性判断和处理的肺纤维化、机化性肺炎（例如，闭塞性细支气管炎）、尘肺、药物相关肺炎、特发性肺炎或在筛选期胸部 CT 显示患有活动性肺炎或肺功能严重受损的受试者；活动性结核； 3. 存在活动性自身免疫病或有自身免疫病病史且可能复发[包括但不局限于自身免疫性肝炎、间质性肺炎、葡萄膜炎、肠炎、垂体炎、血管炎、肾炎、甲状腺功能亢进、甲状腺功能降低（仅通过激素替代治疗可以控制的受试者可入组）]；患有无需系统治疗的皮肤病如白癜风、银屑病、脱发，接受胰岛素治疗的经控制的 I 型糖尿病或在童年期哮喘已完全缓解，成人后无需任何干预的可入组；需要支气管扩张剂进行医学干预的哮喘患者则不能入组； 4. 入组前 2 周内使用免疫抑制剂或全身激素治疗以达到免疫抑制目的（剂量 >10mg/天泼尼松或其他等疗效激素）； 5. 患者有活动性感染、入组前 1 周内有不明原因发热 ≥38.5℃、或基线期白细胞计数 >15×109/L ；入组之前 2 周内口服或静脉给予治疗性抗生素（用药时间不超过 48 小时静脉给予的预防性抗生素除外）； 6. 患者先天或后天免疫功能缺陷（如 HIV 感染者）； 7. 入组前 4 周内接受过减毒活疫苗治疗，或预期于治疗期间或末次给药后 60 天内需要接种此类疫苗； 8. 入组前 6 个月内出现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、重度食管胃底静脉曲张、出血性胃溃疡或患有脉管炎等，基线期若大便潜血阳性，可复查，复查后若仍为阳性，需要进行胃镜检查； 9. 已知存在的遗传性或获得性出血（如凝血功能障碍）或血栓倾向，如血友病病人，凝血机制障碍，血小板减少等；目前正在接受出于治疗目的使用全剂量口服或注射抗凝药物或溶栓药物（允许预防性使用小剂量阿司匹林等）； 10. 入组前 6 个月内发生过动脉血栓栓塞事件，如脑血管意外（包括暂时性缺血性发作、脑出血、脑梗塞）、CTCAE3 级以上的深静脉血栓、肺栓塞等； 11. 有未能良好控制的心脏临床症状或疾病，如：（1）按照纽约心脏病协会（NYHA）标准 II 级以上心脏功能不全或彩色多普勒超声心电图：LVEF（左室射血分数）<50%；（2）不稳定型心绞痛；(3）入组前 1 年内发生过心肌梗死；（4）有临床意义的室上性或室性心律失常需要治疗或干预；（5）静息状态下 QTc> 450ms（男性）； QTc>470ms（女性）； 12. 药物无法控制的高血压（收缩压≥140mmHg 或者舒张压 ≥90mmHg)（基于≥2 次测量获得的 BP 读数的平均值），允许通过使用降压治疗实现上述参数：既往曾出现高血压危象或高血压性脑病； 13. 入组前 6 个月内出现重大血管疾病（例如，需要手术修补或近期有外周动脉血栓形成的主动脉瘤）； 14. 严重、未愈合或裂开的伤口以及活动期溃病或未经治疗的骨折； 15. 入组前 4 周内接受过大手术治疗（诊断除外）或预期需在研究期间进行大手术治疗； 16. 不能吞咽药片、吸收不良综合症或任何影响胃肠吸收的状况； 17. 入组前 6 个月内曾患肠梗阻和/或曾有胃肠道梗阻临床体征或症状，包括与原有疾病有关或需要常规肠外水化、肠外营养或管饲的不完全梗阻。在初始诊断时如果有不完全梗阻/梗阻综合征/肠梗阻体征/症状的患者接受了明确（外科）治疗以消退症状时，经综合评估后患者可入组； 18. 入组前2周内仍在使用强CYP3A4诱导剂（利福平、利福喷丁、苯妥因、卡马西平、巴比妥类或圣约翰草等）或入组前1周内仍在使用强CYP3A4抑制剂（伊曲康唑，酮康唑、伏立康唑、阿扎那韦、利托那韦、克拉霉素、葡萄柚等）； 19. 已知对任何研究药物或辅料过敏者； 20. 入组前 4 周内有参加其他药物临床研究； 21. 妊娠或哺乳期女性； 22. 研究者认为不适合参加该研究的其他因素。

Exclusion criteria：

Known intrahepatic cholangiocarcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma (with more than 30% ICC component), and fibrolamellar carcinoma; other active malignant tumors within 5 years or concurrently with HCC; subjects assessed by the investigator as needing surgery combined with radiofrequency ablation treatment before enrollment. Cured localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostatic carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc., can be enrolled; Currently with interstitial pneumonia or interstitial lung disease, or a history of interstitial pneumonia or interstitial lung disease requiring steroid treatment, or other conditions that may interfere with the judgment and management of immune-related pulmonary toxicity, such as pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or subjects with active pneumonia or severely impaired lung function shown on chest CT during the screening period; active tuberculosis; Presence of active autoimmune disease or a history of autoimmune disease that may recur [including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (subjects who can be controlled with hormone replacement therapy only can be enrolled)]; subjects with skin diseases that do not require systemic treatment such as vitiligo, psoriasis, alopecia, controlled type I diabetes treated with insulin, or asthma in childhood that has completely resolved and does not require any intervention in adulthood can be enrolled; asthma patients requiring bronchodilators for medical intervention cannot be enrolled; Use of immunosuppressants or systemic corticosteroid treatment for immunosuppression within 2 weeks before enrollment (dose >10mg/day prednisone or other equivalent efficacy steroids); Patients with active infection, unexplained fever ≥38.5°C within 1 week before enrollment, or baseline white blood cell count >15×10^9/L; administration of therapeutic antibiotics orally or intravenously within 2 weeks before enrollment (except for prophylactic antibiotics administered intravenously for no more than 48 hours); Patients with congenital or acquired immune function defects (such as HIV-infected individuals); Received treatment with live attenuated vaccines within 4 weeks before enrollment, or expected to require such vaccinations during the treatment period or within 60 days after the last administration; Significant clinical bleeding symptoms or clear bleeding tendency within 6 months before enrollment, such as gastrointestinal bleeding, severe esophageal-gastric varices, hemorrhagic gastric ulcer, or patients with vasculitis, etc., if the baseline fecal occult blood test is positive, re-examination can be done, and if still positive after re-examination, a gastroscopy is required; Known genetic or acquired bleeding tendencies (such as coagulation disorders) or thrombotic tendencies, such as hemophilia patients, coagulation mechanism disorders, thrombocytopenia, etc.; currently receiving full-dose oral or injectable anticoagulant or thrombolytic drugs for therapeutic purposes (preventive use of low-dose aspirin is allowed); Arterial thromboembolic events within 6 months before enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis of grade 3 or above according to CTCAE, pulmonary embolism, etc.; Poorly controlled cardiac clinical symptoms or diseases, such as: (1) cardiac insufficiency of grade II or above according to the New York Heart Association (NYHA) standards or color Doppler echocardiography: LVEF (left ventricular ejection fraction) <50%; (2) unstable angina; (3) myocardial infarction within 1 year before enrollment; (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) QTc>450ms (males); QTc>470ms (females) at rest; Uncontrolled hypertension (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg) (based on the average of ≥2 BP readings), allowed to achieve the above parameters through antihypertensive treatment: history of hypertensive crisis or hypertensive encephalopathy; Major vascular diseases within 6 months before enrollment (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis); Severe, unhealed, or dehisced wounds, and active ulcers or untreated fractures; Received major surgical treatment (except for diagnosis) within 4 weeks before enrollment or expected to require major surgical treatment during the study period; Inability to swallow pills, malabsorption syndrome, or any condition affecting gastrointestinal absorption; History of intestinal obstruction and/or clinical signs or symptoms of gastrointestinal obstruction within 6 months before enrollment, including incomplete obstruction related to the original disease or requiring regular parenteral hydration, parenteral nutrition, or tube feeding. Patients with incomplete obstruction/obstruction syndrome/gastrointestinal obstruction signs/symptoms at the initial diagnosis who have received definitive (surgical) treatment to alleviate symptoms may be enrolled after comprehensive assessment; Still using strong CYP3A4 inducers (rifampicin, rifapentine, phenytoin, carbamazepine, barbiturates, or St. John's wort, etc.) within 2 weeks before enrollment or still using strong CYP3A4 inhibitors (itraconazole, ketoconazole, voriconazole, atazanavir, ritonavir, clarithromycin, grapefruit, etc.) within 1 week before enrollment; Known allergy to any study drug or excipients; Participated in other drug clinical studies within 4 weeks before enrollment; Pregnant or breastfeeding women; Other factors deemed unsuitable for participation in the study by the investigator.

研究实施时间：

Study execute time：

从 From 2024-10-14 00:00:00至 To 2026-10-14 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-10-14 00:00:00 至 To 2026-10-14 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 30

Group：

Experimental group

Sample size：

干预措施：

TACE联合阿得贝利单抗和甲磺酸仑伐替尼

干预措施代码：

Intervention：

TACE combined with Adabelimab and lenvatinib mesylate

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 江苏 

市(区县)：

  

Country：

China

Province：

jiangsu

City：

单位(医院)：

 南京医科大学第一附属医院 

单位级别：

 三甲 

Institution
hospital：

The First Affiliated Hospital of Nanjing Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

6个月无肿瘤进展率

指标类型：

主要指标

Outcome：

PFS6

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

OS(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：

客观缓解率

指标类型：

次要指标

Outcome：

ORR(Objective Response Rate)

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 100 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:

公开/Public

盲法：

Blinding：

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

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）：

无

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

none

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：

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  2024-10-14 09:01:34