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：	ChiCTR2400094431
最近更新日期： Date of Last Refreshed on：	2024-12-23 15:18:21
注册时间： Date of Registration：	2024-12-23 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	肝动脉灌注化疗（HAIC）联合阿得贝利单抗和贝伐珠单抗一线治疗晚期肝细胞癌（HCC）合并门静脉癌栓（PVTT）的一项开放性，单臂，探索性临床研究
Public title：	An Open, Single-Arm, Exploratory Clinical Study of Hepatic Artery Infusion Chemotherapy (HAIC) in Combination with Adebrelimab and Bevacizumab for First-Line Treatment of Advanced Hepatocellular Carcinoma (HCC) with Portal Vein Thrombosis (PVTT)
注册题目简写：
English Acronym：
研究课题的正式科学名称：	肝动脉灌注化疗（HAIC）联合阿得贝利单抗和贝伐珠单抗一线治疗晚期肝细胞癌（HCC）合并门静脉癌栓（PVTT）的一项开放性，单臂，探索性临床研究
Scientific title：	An Open, Single-Arm, Exploratory Clinical Study of Hepatic Artery Infusion Chemotherapy (HAIC) in Combination with Adebrelimab and Bevacizumab for First-Line Treatment of Advanced Hepatocellular Carcinoma (HCC) with Portal Vein Thrombosis (PVTT)
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：	朱震宇	研究负责人：	朱震宇
Applicant：	Zhenyu Zhu	Study leader：	Zhenyu Zhu
申请注册联系人电话： Applicant telephone：	+86 138 1087 7106	研究负责人电话： Study leader's telephone：	+86 138 1087 7106
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：	zhuzy302@163.com	研究负责人电子邮件： Study leader's E-mail：	zhuzy302@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：	北京市丰台区西四环中路100号	研究负责人通讯地址：	北京市丰台区西四环中路100号
Applicant address：	NO.100, West Fourth Ring Middle Road, Beijing	Study leader's address：	NO.100, West Fourth Ring Middle Road, Beijing
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：	中国人民解放军总医院第五医学中心
Applicant's institution：	the Fifth Medical Center of Chinese PLA General Hospital
研究负责人所在单位：	中国人民解放军总医院第五医学中心
Affiliation of the Leader：	the Fifth Medical Center of Chinese PLA General 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：	KY-2024-10-168-1;KY-2024-10-168-2	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：	中国人民总医院第五医学中心伦理委员会
Name of the ethic committee：	Medical Ethics Committee of the the Fifth Medical Center of Chinese PLA General Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2024-11-06 00:00:00
伦理委员会联系人：	张昕洁
Contact Name of the ethic committee：	Xinjie Zhang
伦理委员会联系地址：	北京市丰台区东大街8号
Contact Address of the ethic committee：	No.8, Dongda Street, Fengtai District, Beijing
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 10 6694 7798	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：

中国人民解放军总医院第五医学中心

Primary sponsor：

The Fifth Medical Center of Chinese PLA General Hospital

研究实施负责（组长）单位地址：

北京市丰台区西四环中路100号

Primary sponsor's address：

NO.100, West Fourth Ring Middle Road, Beijing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	中国人民解放军总医院第五医学中心	具体地址：	北京市丰台区西四环中路100号
Institution hospital：	the Fifth Medical Center of Chinese PLA General Hospital	Address：	NO.100, West Fourth Ring Middle Road, Beijing

经费或物资来源：

国家卫生健康委医药卫生科技发展研究中心

Source(s) of funding：

National Health Commission Medical and Health Science and Technology Development Research Center

研究疾病：

肝癌

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：

其它

Study phase：

N/A

研究设计：

单臂

Study design：

Single arm

研究目的：

评价HAIC联合阿得贝利单抗和贝伐珠单抗一线治疗晚期HCC合并PVTT患者的有效性和安全性。

Objectives of Study：

To evaluate the efficacy and safety of HAIC in combination with Adebrelimab and bevacizumab for the first-line treatment of patients with advanced HCC combined with PVTT.

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. 年龄为18-75岁（包含18和75）（以签署知情同意当日计算），男女皆可；
3.影像学CT/MRI确诊的肝细胞癌患者；
4.巴塞罗那临床肝癌分期（BCLC，见附件1）C期，且不适合手术，或经过手术和/或局部治疗后进展；腹部核磁增强或腹部CT增强证实合并门脉癌栓Vp 3，或Vp 4）；
5.局部治疗后进展的患者，局部治疗（包括但不限于手术、放疗、肝动脉栓塞、TACE、肝动脉灌注、射频消融、冷冻消融或经皮乙醇注射）至少在基线影像学扫描前4周已完成，且局部治疗引起的毒性反应（脱发除外）必须恢复至美国国家癌症研究所-不良事件通用术语标准第5.0版（NCI-CTCAE v5.0）评级<=1级；
6.既往未接受过任何针对HCC的系统治疗
7.至少有一个可测量病灶（根据RECIST v1.1标准）
8. Child-Pugh肝功能分级（见附件2）：A、或B级
9.东部肿瘤协作组（ECOG）体力状况评分为0～1分（ECOG评分标准见附件3）；
10.预期生存期 >= 12周；
11.主要器官功能基本正常，严重血液、心、肺、肝、肾、骨髓等功能异常和免疫缺陷疾病，符合方案要求：
	血常规检查：（除外血红蛋白，筛查前14天内未输血、未使用粒细胞集落刺激因子[G-CSF]、7天内未使用纠正治疗）
        血红蛋白 >= 90 g/L；
	中性粒细胞计数 >= 1.5×109/L；
	血小板计数 >=50×109/L；
	生化检查：（14天内未输白蛋白）
	血清白蛋白 >= 29 g/L；
	丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）<=2.5倍正常值上限（ULN）；
	总胆红素（TBIL）<= 1.5倍ULN；
	肌酐Cr <= 1.5倍ULN或Cr清除率 > 50 mL/min（Cockcroft-Gault公式如下）
男性：Cr清除率=((140-年龄)×体重)/(72×血Cr) 
女性：Cr清除率=((140-年龄)×体重)/(72×血Cr) × 0.85 
体重单位：kg；血Cr单位：mg/mL；
	尿蛋白 < 2+（若尿蛋白 ≥ 2+，可以进行24小时（h）尿蛋白定量，24h尿蛋白定量<1.0 g 可以入组）；
	凝血功能：活化部分凝血活酶时间（APTT）和国际标准化比值（INR）<= 1.5×ULN（对于使用稳定剂量的抗凝治疗如低分子肝素或者华法林且INR在抗凝血剂的预期治疗范围内可以筛选）；
	促甲状腺激素（TSH）<= ULN；如果异常应考察T3和T4水平，T3和T4水平水平正常则可以入选；
	心脏彩超：左室射血分数（LVEF）大于等于60%。
12.若患者患有活动性乙型肝炎病毒（HBV）感染：HBV-脱氧核糖核酸（DNA）必须＜ 2×103 IU/mL且愿意在研究期间全程接受抗病毒治疗（依据当地标准治疗进行治疗，例如恩替卡韦），在监测病毒拷贝数的情况下，由医生根据患者个体情况判断是否符合入组；
丙型肝炎病毒（HCV）核糖核酸（RNA）阳性患者必须按当地标准治疗指南接受抗病毒治疗且肝功能在CTCAE 1级升高以内；
13.有生育能力的女性：必须同意从签署知情同意书开始直到研究药物末次给药后至少120天内禁欲（避免异性性交）或使用可靠、有效方法避孕。且在开始研究治疗前的7天内血清HCG检查必须为阴性；而且必须为非哺乳期。如果女性患者已来月经、尚未达到绝经后状态（连续无月经时间>=12个月，除绝经之外未发现其他原因），且未接受过绝育手术（如子宫切除术、双侧输卵管结扎术或双侧卵巢切除术），则认为该患者有生育能力。
14.对于伴侣为育龄妇女的男性患者，必须同意从签署知情同意书开始直到研究药物末次给药后至少120天内禁欲，或使用可靠、有效方法避孕。在同一时间段内男性受试者也必须同意不捐精子。伴侣已怀孕的男性受试者须使用避孕套，无须再采用其它避孕方法。

Inclusion criteria

1.Patients voluntarily enrolled in this study by signing an informed consent form;
2.Aged 18-75 years (inclusive of 18 and 75) (calculated on the date of signing the informed consent), both male and female;
3.Patients with hepatocellular carcinoma confirmed by imaging CT/MRI;
4. BCLC C and not suitable for surgery, or progressed after surgery and/or local treatment; abdominal nuclear magnetic enhancement or abdominal CT enhancement confirming combined portal cancer embolization Vp 3, or Vp 4);
5.For patients who have progressed after local therapy, local therapy (including, but not limited to, surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) has been completed at least 4 weeks prior to the baseline imaging scan, and toxic reactions (other than alopecia) resulting from the local therapy must have been recovered to the National Cancer Institute-Common Terminology Criteria for Adverse Events, version 5.0 ( NCI-CTCAE v5.0) rating <=Grade 1;
6.Not have received any prior systemic therapy for HCC
7. At least one measurable lesion (according to RECIST v1.1 criteria)
8. Child-Pugh Liver Function Classification (see Appendix 2): A, or B.
9. Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1 (see Annex 3 for ECOG scoring criteria)
10. Expected survival >= 12 weeks;
11. The function of major organs is basically normal, and severe blood, heart, lung, liver, kidney, bone marrow and other functional abnormalities and immunodeficiency diseases meet the requirements of the program:
	Routine blood tests: (excluding hemoglobin, no blood transfusion within 14 days prior to screening, no use of granulocyte colony-stimulating factor [G-CSF], no corrective therapy within 7 days)
        Hemoglobin > = 90 g/L;
	Neutrophil count > = 1.5×109/L;
	Platelet count >=50×109/L;
	Biochemical tests: (no albumin transfusion within 14 days)
	serum albumin > = 29 g/L;
	alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 times the upper limit of normal (ULN);
	Total bilirubin (TBIL) < = 1.5 times ULN;
	Creatinine Cr < = 1.5-fold ULN or Cr clearance > 50 mL/min (Cockcroft-Gault formula below)
Male: Cr clearance = ((140-age) × weight) / (72× blood Cr) 
Female: Cr clearance = ((140-age)× weight)/(72× blood Cr) × 0.85 
Weight unit: kg; Blood Cr unit: mg/mL;
	Urine protein < 2+ (if urine protein is ≥ 2+, 24-hour (h) urine protein quantification can be performed, and 24-hour urine protein quantification <1.0 g can be enrolled);
	Coagulation function: activated partial thromboplastin time (APTT) and international normalized ratio (INR) < = 1.5× ULN (for anticoagulant therapy at stable doses such as low molecular weight heparin or warfarin, and INR is within the expected therapeutic range of anticoagulants, screening can be made);
	Thyroid-stimulating hormone (TSH) < = ULN; T3 and T4 levels should be examined if abnormalities occur, and normal T3 and T4 levels can be selected;
	Cardiac ultrasound: left ventricular ejection fraction (LVEF) greater than or equal to 60%.
12. If the patient has active hepatitis B virus (HBV) infection: HBV-deoxyribonucleic acid (DNA) must be < 2×103 IU/mL and willing to receive antiviral therapy throughout the study period (treatment according to local standard treatment, such as entecavir), and the doctor will judge whether it is eligible for enrollment according to the patient's individual condition under the condition of monitoring the viral copy number;
Hepatitis C virus (HCV) ribonucleic acid (RNA)-positive patients must be on antiviral therapy according to local standard treatment guidelines and have elevated liver function within CTCAE grade 1;
13. Females of childbearing potential: Must agree to abstain from sexual intercourse (refrain from heterosexual intercourse) or use a reliable, effective method of contraception for at least 120 days from the time of signing the informed consent form until at least 120 days after the last dose of study drug. and must have a negative serum HCG test within 7 days prior to starting study treatment; and must be non-lactating. A woman is considered to be of childbearing potential if she has menstruated, has not yet reached postmenopausal status (continuous period-free > = 12 months, no cause other than menopause found), and has not undergone sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
14. For male patients whose partner is a woman of childbearing potential, must agree to abstain from sexual intercourse or use a reliable, effective method of contraception from the time of signing the informed consent form until at least 120 days after the last dose of study drug. Male subjects must also agree not to donate sperm during the same time period. Male subjects whose partner is pregnant must use a condom and no other contraceptive method is required.

排除标准：

1. 已知肝胆管细胞癌、肉瘤样HCC、混合细胞癌及纤维板层细胞癌；5年内或同时患有，除HCC之外的，其它活动性恶性肿瘤。已治愈的局限性肿瘤，如皮肤基底细胞癌、皮肤鳞癌、表浅膀胱癌、前列腺原位癌、宫颈原位癌、乳腺原位癌等可以入组； 2.准备进行或者既往接受过器官或同种异基因骨髓移植的患者； 3.在开始研究治疗之前28天内接受过其他试验用药物治疗； 4.有临床症状的中度、重度腹水即需要治疗性的穿刺、引流者或Child-Pugh评分>2（仅影像学显示少量腹水但不伴有临床症状者除外）；不受控制或中等量及以上的胸腔积液、心包积液； 5.研究治疗开始前6个月内有消化道出血病史或具有明确的胃肠道出血倾向，如：有出血危险的或重度食管胃底静脉曲张、有局部活动性消化道溃疡病灶、持续大便潜血阳性不可入组（基线期若大便潜血阳性，可复查，复查后若仍为阳性，需要进行胃十二指肠镜检（EGD），若EGD提示出血风险的食管胃底静脉曲张则不能入组）； 6. 研究治疗开始前6个月内出现过腹部瘘管、胃肠道穿孔或腹腔脓肿； 7. 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；目前正在或近期（研究治疗开始前10天内）曾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、低分子肝素）； 8. 目前正在使用或近期曾使用（研究治疗开始前10天内）阿司匹林（> 325mg/天(最大抗血小板剂量）或双嘧达莫、噻氯匹定、氯吡格雷和西洛他唑治疗； 9.研究治疗开始前6个月内发生过血栓形成或栓塞事件，例如脑血管意外（包括短暂性脑缺血发作、脑出血、脑梗塞）、肺栓塞等； 10.有未能良好控制的心脏临床症状或疾病，如：按照纽约心脏病协会（NYHA）标准II级以上心脏功能不全或心脏彩超检查：LVEF（左室射血分数）<50%；不稳定型心绞痛；研究治疗开始前1年内发生过心肌梗死；有临床意义的室上性或室性心律失常需要治疗或干预； QTc > 450ms（男性）；QTc > 470ms （女性）（QTc间期以Fridericia公式计算；若QTc异常，可间隔2分钟连续检测三次，取其平均值）； 11.患有高血压，且经降压药物治疗无法获得良好控制（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； 12.在研究治疗开始前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）；严重、未愈合或裂开的伤口以及活动期溃疡或未经治疗的骨折；在研究治疗开始前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； 13.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；在开始研究治疗之前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，患者或许可入组研究； 14.有证据表明存在无法通过穿刺或近期外科手术解释说明的腹内积气； 15.既往或目前存在中枢神经系统转移； 16.有肝性脑病病史者；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计算机断层扫描（CT）图上可见活动性肺炎证据或肺功能严重受损的受试者，允许放射野曾有辐射性肺炎；活动性结核； 17.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纳入]）；受试者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纳入；需要支气管扩张剂进行医学干预的哮喘患者则不能纳入； 18.在开始研究治疗之前14天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>10 mg/天泼尼松或其他等疗效激素）； 19. 在开始研究治疗之前14天内使用强CYP3A4/ CYP2C19诱导剂包括利福平（及其类似物）和贯叶连翘或强CYP3A4/ CYP2C19抑制剂； 20.已知对任何单克隆抗体、抗血管生成靶向药物有严重过敏史； 21.在开始研究治疗之前4周内有重度感染，包括但不限于因感染、菌血症或重度肺炎并发症而住院治疗；在开始研究治疗之前2周内口服或静脉给予治疗性抗生素（接受预防性抗生素（例如，预防尿路感染或慢性阻塞性肺病加重的患者有资格参与研究）； 22.患者先天或后天免疫功能缺陷（如HIV感染者）； 23.合并乙肝及丙肝共同感染； 24.既往曾接受过其他抗PD-1抗体治疗或其他针对PD-1/PD-L1的免疫治疗，或既往接受过贝伐珠单抗治疗； 25. 在开始研究治疗之前28天内接受过减毒活疫苗治疗，或预期于阿得贝利单抗治疗期间或阿得贝利单抗末次给药后60天内需要接种此类疫苗 26.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：

1. Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar cell carcinoma; Active malignancy other than HCC within 5 years or at the same time. Cured localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, etc., can be enrolled; 2. Patients who are ready to undergo or have previously received organ or allogeneic bone marrow transplantation; 3. Received other investigational drug treatment within 28 days prior to initiation of study treatment; 4. Clinically symptomatic moderate or severe ascites, i.e., those who require therapeutic puncture and drainage or a Child-Pugh score of >2 (except for those who only show a small amount of ascites on imaging but are not accompanied by clinical symptoms); Uncontrolled or moderate or above pleural effusion, pericardial effusion; 5. History of gastrointestinal bleeding or definite gastrointestinal bleeding tendency within 6 months before the start of study treatment, such as: bleeding risk or severe esophageal and gastric varices, locally active peptic ulcer lesions, and persistent fecal occult blood are not eligible for enrollment (if fecal occult blood is positive in the baseline period, it can be retested, and if it is still positive after reexamination, gastroduodenoscopy (EGD) is required, and esophageal and gastric varices with bleeding risk indicated by EGD cannot be enrolled); 6. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the start of study treatment; 7. Known hereditary or acquired bleeding (e.g., coagulation dysfunction) or thrombotic tendency, such as hemophilia patients; Current or recent (within 10 days prior to the start of study treatment) prior to the use of full-dose oral or injectable anticoagulant drugs or thrombolytic drugs for therapeutic purposes (prophylactic use of low-dose aspirin, low molecular weight heparin is allowed); 8. Current use or recent prior use (within 10 days prior to initiation of study treatment) aspirin (> 325mg/day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazole; 9. Thrombosis or embolic events within 6 months before the start of study treatment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.; 10. Have uncontrolled cardiac clinical symptoms or diseases, such as: Cardiac insufficiency or cardiac color ultrasound examination according to New York Heart Association (NYHA) criteria above grade II: LVEF (left ventricular ejection fraction) <50%; unstable angina; Myocardial infarction within 1 year prior to the start of study treatment; Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; QTc > 450ms (males); QTc > 470ms (female) (QTc interval calculated by Fridericia's formula; If the QTc is abnormal, it can be tested three times continuously at an interval of 2 minutes, and the average value can be taken); 11. Patients with hypertension that are not well controlled with antihypertensive medication (systolic blood pressure > = 140 mmHg or diastolic blood pressure > = 90 mmHg) (based on > = average of BP readings obtained from 2 measurements), allowing the above parameters to be achieved through the use of antihypertensive therapy; previous hypertensive crisis or hypertensive encephalopathy; 12. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment; severe, non-healing or dehiscence wounds and active ulcers or untreated fractures; Has undergone major surgical treatment (other than diagnosis) within 4 weeks prior to the start of study treatment or is expected to require major surgical treatment during the study; 13. Inability to swallow tablets, malabsorption syndrome, or any condition that affects gastrointestinal absorption; Has had intestinal obstruction and/or had clinical signs or symptoms of gastrointestinal obstruction within 6 months prior to initiation of study treatment, including incomplete obstruction related to a pre-existing condition or requiring routine parenteral hydration, parenteral nutrition, or tube feeding: Patients may be allowed to be enrolled in the study if at the time of initial diagnosis if the patient has received definitive (surgical) therapy to resolve symptoms; 14. Evidence of the presence of intra-abdominal pneumata that cannot be explained by paracentesis or recent surgical surgery; 15. Previous or current central nervous system metastases; 16. Those with a history of hepatic encephalopathy; Subjects with current interstitial pneumonia or interstitial lung disease, or a history of interstitial pneumonia or interstitial lung disease requiring hormonal therapy, or other pulmonary fibrosis, organizing pneumonitis (e.g., bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia, idiopathic pneumonitis, or evidence of active pneumonia or severe impairment of lung function on the chest computed tomography (CT) diagram during the screening period, are allowed to have radiation pneumonitis in the radiation field; Active tuberculosis; 17. Presence of active autoimmune disease or history of autoimmune disease that may relapse (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [subjects who can be controlled by hormone replacement therapy alone can be included]); Subjects with skin diseases such as vitiligo, psoriasis, alopecia, controlled type I diabetes treated with insulin or complete remission of asthma in childhood, without any intervention after adulthood, may be included; Patients with asthma requiring medical intervention with bronchodilators could not be included; 18. Use of immunosuppressants or systemic hormonal therapy for immunosuppressive purposes within 14 days prior to initiation of study treatment (dose> 10 mg/day prednisone or other equivalent efficacy hormones); 19. Use of strong CYP3A4/CYP2C19 inducers, including rifampicin (and its analogues) and St. John's wort or strong CYP3A4/CYP2C19 inhibitors, within 14 days prior to initiation of study treatment; 20. Known history of severe allergy to any monoclonal antibody or anti-angiogenic targeted drugs; 21. Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; Therapeutic antibiotics given orally or intravenously within 2 weeks prior to initiation of study treatment (receiving prophylactic antibiotics (e.g., patients who prevent urinary tract infections or exacerbations of chronic obstructive pulmonary disease are eligible to participate in the study); 22. Patients with congenital or acquired immunodeficiency (such as HIV infection); 23. Co-infection with hepatitis B and C; 24. Previous treatment with other anti-PD-1 antibodies or other immunotherapy against PD-1/PD-L1, or prior treatment with bevacizumab; 25. Treatment with a live attenuated vaccine within 28 days prior to initiation of study treatment, or anticipated need for such vaccine during treatment with adebelimab or within 60 days after the last dose of adebelimab 26. As judged by the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illnesses) that require concurrent treatment, serious laboratory examination abnormalities, accompanied by family or social factors, which will affect the patient's safety.

研究实施时间：

Study execute time：

从 From 2024-12-31 00:00:00至 To 2026-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-12-31 00:00:00 至 To 2026-06-15 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	35
Group：	Experimental group	Sample size：	35
干预措施：	HAIC治疗每3周一次，最多治疗6次；阿得贝利单抗，20mg/kg，静脉滴注，D1， Q3W，联合贝伐珠单抗，15mg/kg, 静脉滴注， Q3W	干预措施代码：
Intervention：	HAIC treatment every 3 weeks for up to 6 treatments;Adebrelimab, 20 mg/kg, IV, D1, Q3W, in combination with bevacizumab, 15 mg/kg, IV, Q3W	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	中国人民解放军总医院第五医学中心	单位级别：	三甲
Institution hospital：	the Fifth Medical Center of Chinese PLA General Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	进展自由生存	指标类型：	主要指标
Outcome：	Progress Free Survival	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：	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：	Objective 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：	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：	进步时间	指标类型：	次要指标
Outcome：	Time to Progression	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	响应持续时间	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：	不良事件	指标类型：	次要指标
Outcome：	Adverse Events	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	使用后保存	说明
Fate of sample：	Preservation after use	Note：

标本中文名：	肝脏组织	组织：
Sample Name：	Liver tissue	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation 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）：

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：	无
Blinding：	None
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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：	CRF
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：	有/Yes
注册人： Name of Registration：	2024-12-23 15:18:14