ChiCTR2500102333 版本V1.0 版本创建时间2025/05/13 14:50:34 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：

 ChiCTR2500102333 

最近更新日期：

Date of Last Refreshed on：

 2025-05-13 14:50:06 

注册时间：

Date of Registration：

 2025-05-13 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

阿得贝利单抗和安罗替尼联合肝动脉灌注化疗或静脉化疗用于晚期胆道肿瘤的一线治疗：一项随机、开放标签的临床研究

Public title：

Adbelizumab and anlotinib in combination with hepatic arterial infusion or intravenous chemotherapy for first-line treatment of advanced biliary tract tumors: a randomized, open-label clinical study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

阿得贝利单抗和安罗替尼联合肝动脉灌注化疗或静脉化疗用于晚期胆道肿瘤的一线治疗：一项随机、开放标签的临床研究

Scientific title：

Adbelizumab and anlotinib in combination with hepatic arterial infusion or intravenous chemotherapy for first-line treatment of advanced biliary tract tumors: a randomized, open-label 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：

罗秋枫 

研究负责人：

马劼 

Applicant：

Qiufeng Luo  

Study leader：

Jie Ma 

申请注册联系人电话：

Applicant telephone：

 +86 184 0772 8817

研究负责人电话：

Study leader's
telephone：

+86 139 7885 1892

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：

 hrark123456@163.com

研究负责人电子邮件：

Study leader's E-mail：

 majie086@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：

广西南宁市青秀区双拥路6号

研究负责人通讯地址：

广西南宁市青秀区双拥路6号

Applicant address：

6 Shuangyong Road, Qingxiu District, Nanning, Guangxi

Study leader's address：

6 Shuangyong Road, Qingxiu District, Nanning, Guangxi

申请注册联系人邮政编码：

Applicant postcode：

 530000

研究负责人邮政编码：

Study leader's postcode：

 530000

申请人所在单位：

广西医科大学第一附属医院

Applicant's institution：

The First Affiliated Hospital of Guangxi Medical University

研究负责人所在单位：

广西医科大学第一附属医院

Affiliation of the Leader：

The First Affiliated Hospital of Guangxi Medical University

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-K229-01

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：

广西医科大学第一附属医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-06-26 00:00:00

伦理委员会联系人：

何玲

Contact Name of the ethic committee：

Ling He

伦理委员会联系地址：

广西南宁市青秀区双拥路6号

Contact Address of the ethic committee：

6 Shuangyong Road, Qingxiu District, Nanning, Guangxi

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 771 535 6557

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：

广西医科大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Guangxi Medical University

研究实施负责（组长）单位地址：

广西南宁市青秀区双拥路6号

Primary sponsor's address：

6 Shuangyong Road, Qingxiu District, Nanning, Guangxi

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

广西壮族自治区

市(区县)：

南宁

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

Nanning

单位(医院)：

广西医科大学第一附属医院

具体地址：

广西南宁市青秀区双拥路6号

Institution
hospital：

The First Affiliated Hospital of Guangxi Medical University

Address：

6 Shuangyong Road, Qingxiu District, Nanning, Guangxi

经费或物资来源：

自筹经费

Source(s) of funding：

Self-financing

研究疾病：

胆道癌  

Target disease：

Carcinoma of biliary tract

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：

1，通过评估6个月无进展生存率（6-m PFS%）来评价阿得贝利单抗和安罗替尼联合肝动脉灌注化疗或静脉化疗用于晚期胆道肿瘤的一线治疗的有效性。 次要研究目的： 2，通过评估无进展生存期（PFS）、疾病进展时间（TTP）、疾病控制率（DCR）、客观缓解率（ORR）、缓解持续时间（DoR）和总生存期（OS）评价阿得贝利单抗和安罗替尼联合肝动脉灌注化疗或静脉化疗用于晚期胆道肿瘤的一线治疗的有效性； 3，评价阿得贝利单抗和安罗替尼联合肝动脉灌注化疗或静脉化疗用于晚期胆道肿瘤的一线治疗的安全性。 探索性研究目的 4，探索生物标记物与联合治疗方案疗效之间的相关性。 对比不同给药方式的化疗药物，联合阿得贝利单抗和安罗替尼，用于晚期胆道肿瘤一线治疗的疗效。  

Objectives of Study：

1. To evaluate the effectiveness of adebelizumab and anrotinib combined with hepatic arterial infusion chemotherapy or intravenous chemotherapy in the first-line treatment of advanced biliary tract tumors by evaluating the 6-month progression-free survival rate (6-m PFS%). Secondary research purposes: 2. To evaluate the effectiveness of adebelizumab and anrotinib combined with hepatic arterial infusion chemotherapy or intravenous chemotherapy in the first-line treatment of advanced biliary tumors by evaluating progression-free survival (PFS), disease progression time (TTP), disease control rate (DCR), objective remission rate (ORR), remission duration (DoR) and overall survival (OS); 3. To evaluate the safety of adebelizumab and anrotinib combined with hepatic arterial infusion chemotherapy or intravenous chemotherapy in the first-line treatment of advanced biliary tract tumors. Exploratory research Objective 4: To explore the correlation between biomarkers and the efficacy of combined therapy. To compare the efficacy of chemotherapy drugs with different administration methods combined with adebelizumab and anrotinib in the first-line treatment of advanced biliary tract tumors

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) >=18岁（以签署知情同意当日计算），男女皆可； 3) 经病理组织学或细胞学确诊的晚期胆道恶性肿瘤患者； 4) 受试者必须能够提供新鲜或存档的肿瘤组织（福尔马林固定、石蜡包埋的[FFPE]组织块或至少5张未染色的FFPE玻片）及其病理学报告。如果受试 者能提供的未染色玻片不到5张或肿瘤组织不可用（例如，因为既往诊断性测试而用尽），在讨论之后，根据具体情况可能允许入组； 5) 受试者不适合手术，或经过手术和/或局部治疗后进展； 6) 局部治疗后进展的患者，局部治疗（包括但不限于手术、放疗、动脉栓塞、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-CTCAEv5.0）评级<=1级； 7) 既往未接受过任何针对BTC的系统治疗; 8) 至少有一个可测量病灶（根据RECISTv1.1要求，该可测量病灶螺旋CT扫描长径≥10mm或肿大淋巴结短径>=15mm；既往接受过局部治疗的病灶， 根据RECISTv1.1标准明确进展后可作为靶病灶）; 9) 东部肿瘤协作组（ECOG）体力状况评分为0～2分（ECOG评分标准见附件1）； 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： a) 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） i.血红蛋白>=90g/L； ii.中性粒细胞计数>=1.5×10^9/L； iii.血小板计数>=50×10^9/L； b) 生化检查：（14天内未输白蛋白） i.血清白蛋白>=29g/L； ii.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）； iii.总胆红素（TBIL）<=1.5倍ULN； iv.肌酐Cr<=1.5倍ULN或Cr清除率>50mL/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； v.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<1.0g可以入组）； c) 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）； d) 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； e) 心脏彩超：左室射血分数（LVEF）大于等于60%; 12) 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。 13) 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 join this study and sign an informed consent form; 2) Aged 18 years or older (calculated as of the date of signing the informed consent), both males and females can participate; 3) Patients with pathologically diagnosed advanced biliary malignancies; 4) Subjects must be able to provide fresh or archived tumor tissue (formalin-fixed, paraffin-embedded [FFPE] tissue blocks or at least 5 unstained FFPE slides) and their pathology reports. If the number of unstained slides provided by the subject is less than 5 or the tumor tissue is unavailable (e.g., depleted due to previous diagnostic testing), enrollment may be permitted depending on the circumstances after discussion; 5) Subjects who are not suitable for surgery or have progressed after surgery and/or local treatment; 6) For patients who have progressed after local treatment, the local treatment (including but not limited to surgery, radiotherapy, arterial embolization, arterial infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) must have been completed at least 4 weeks prior to the baseline imaging scan, and any toxicities resulting from the local treatment (except for hair loss) must have recovered to a rating of <= Grade 1 according to the National Cancer Institute - Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAEv5.0); 7) No prior systemic treatment for BTC; 8) At least one measurable lesion (according to RECIST v1.1 requirements, the measurable lesion must have a long diameter of >=10mm on spiral CT scan or a short diameter of enlarged lymph nodes of >=15mm; lesions that have previously undergone local treatment can be considered target lesions if they show clear progression according to RECIST v1.1 standards); 9) Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 (ECOG scoring standards are in Appendix 1); 10) Expected lifespan of >=12 weeks; 11) Basic normal function of major organs, with no severe abnormalities in blood, heart, lung, liver, kidney, bone marrow, etc., and no immunodeficiency diseases, meeting the protocol requirements: a) Complete blood count examination: (excluding hemoglobin, no blood transfusions, use of Granulocyte Colony-Stimulating Factor [G-CSF] in the past 14 days, and no corrective treatment in the past 7 days); i. Hemoglobin >= 90 g/L; ii. Neutrophil count >= 1.5 × 10^9/L; iii. Platelet count >= 50 × 10^9/L; b) Biochemical tests: (no albumin transfusion within 14 days) i. Serum albumin >= 29 g/L; ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 times the upper limit of normal (ULN); iii. Total bilirubin (TBIL) <= 1.5 times ULN; iv. Creatinine (Cr) <= 1.5 times ULN or Cr clearance > 50 mL/min (Cockcroft-Gault formula as follows): Male: Cr clearance = ((140 - age) × weight) / (72 × serum Cr) Female: Cr clearance = ((140 - age) × weight) / (72 × serum Cr) × 0.85 Weight units: kg; Serum Cr units: mg/mL; v. Urine protein < 2 (if urine protein >= 2, a 24-hour urine protein quantification may be performed, and if 24h urine protein quantification < 1.0 g, can be included); c) Coagulation function: Activated partial thromboplastin time (APTT) and International Normalized Ratio (INR) <= 1.5 × ULN (for those on stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin and INR in the expected therapeutic range for anticoagulants can be screened); d) Thyroid-stimulating hormone (TSH) <= ULN; if abnormal, T3 and T4 levels should be checked, and if T3 and T4 levels are normal, may be included; e) Cardiac ultrasound: Left ventricular ejection fraction (LVEF) greater than or equal to 60%; 12) Women of childbearing potential: Must agree to refrain from sexual intercourse (avoid heterosexual intercourse) or use a reliable and effective method of contraception for at least 120 days from the signing of the informed consent form until the last administration of the investigational drug. Additionally, a negative serum HCG test must be confirmed within 7 days prior to starting the study treatment; they must also not be breastfeeding. If a female patient has started menstruating, has not reached a postmenopausal state (defined as no menstruation for >= 12 months with no other reasons for amenorrhea), and has not undergone sterilization (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), then the patient is considered to be of childbearing potential; 13) For male patients with partners who are women of childbearing potential, they must agree to refrain from sexual intercourse from the signing of the informed consent form until at least 120 days after the last administration of the investigational drug, or use a reliable and effective method of contraception. During the same period, male subjects must also agree not to donate sperm. Male subjects whose partners are already pregnant must use condoms and do not need to use additional contraceptive methods.

排除标准：

1: ? 5年内或同时患有除BTC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: ? 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： 8: ? 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）； 9: ? 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 10: ? 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； 11:有未能良好控制的心脏临床症状或疾病，如： a)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%； b)不稳定型心绞痛； c)研究治疗开始前1年内发生过心肌梗死； d)有临床意义的室上性或室性心律失常需要治疗或干预； e)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）； 12: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； 13: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； 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；涉及主要气道或血管的转移性疾病（比如由于肿瘤侵犯导致完全闭塞的门静脉主干或腔静脉需要排除入组，门静脉主干是指脾静脉和肠系膜上静脉的汇合处以及肝门静脉分为左右支的分支处）或位于中心的大体积纵隔肿瘤块（距隆嵴<30 mm）； 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:已知对任何单克隆抗体药物有严重过敏史； 20:无法正常吞咽药片，或存在胃肠功能异常，经研究者判断可能影响药物吸收者； 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: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； 25: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.Have other active malignant tumors except BTC within 5 years or at the same time. Localized tumors that have been cured, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, prostate cancer in situ, cervical cancer in situ, breast cancer in situ, etc., can be included in the group; 2.Patients who are about to undergo or have previously received organ or allogeneic bone marrow transplantation; 3.Have been treated with other experimental drugs within 28 days before starting the study treatment; 4.Moderate and severe ascites with clinical symptoms requires therapeutic puncture, drainage or Child-Pugh score > 2 (except 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 and pericardial effusion; 5.There is a history of gastrointestinal bleeding or a clear tendency of gastrointestinal bleeding within 6 months before the start of the study treatment, such as: bleeding-risk or severe esophageal and gastric varices, local active gastrointestinal ulcer lesions, and persistent fecal occult blood positive. You can not enter the group (if the fecal occult blood is positive in the baseline period, you can recheck it, if it is still positive after the recheck, you need to have a gastroscopy (EGD), and if the esophageal and gastric varices indicate the risk of bleeding, you can not enter the group); 6.Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within 6 months before the start of the study treatment; 7.Have suffered from intestinal obstruction and/or clinical signs or symptoms of gastrointestinal obstruction within 6 months before starting the study and treatment, including incomplete obstruction related to the original disease or requiring routine parenteral hydration, parenteral nutrition or tube feeding; 8.Known hereditary or acquired bleeding (such as coagulation dysfunction) or thrombosis tendency, such as hemophilia patients; At present, or in the near future (within 10 days before the start of the study treatment), full-dose oral or injection anticoagulants or thrombolytic drugs have been used for therapeutic purposes (low-dose aspirin and low-molecular-weight heparin are allowed for preventive use); 9.Aspirin (> 325mg/ day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazol are currently being used or recently used (within 10 days before the start of study treatment); 10.Thrombosis or embolism occurred within 6 months before the start of study treatment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction) and pulmonary embolism; 11.There are poorly controlled clinical symptoms or diseases of the heart, such as: a) According to the standards of the New York Heart Association (NYHA) for grade II or above cardiac insufficiency or echocardiography examination: LVEF (left ventricular ejection fraction) <50%; b) Unstable angina pectoris c) Myocardial infarction occurred within one year before the start of the study treatment; d) Supraventricular or ventricular arrhythmias of clinical significance require treatment or intervention; e)QTc > 450ms (male); QTc > 470ms (for females) (The QTc interval is calculated using the Fridericia formula; If the QTc is abnormal, three consecutive tests can be conducted at intervals of 2 minutes, and the average value can be taken. 12. Patients with hypertension who have not achieved good control after antihypertensive drug treatment (systolic blood pressure >= 140mmHg or diastolic blood pressure >= 90mmHg) (based on the average of BP readings obtained from >=2 measurements) are allowed to achieve the above parameters through antihypertensive treatment. There has been a history of hypertensive crisis or hypertensive encephalopathy; 13.Major vascular diseases occurred within 6 months before the start of the study treatment (for example, aortic aneurysms requiring surgical repair or with recent peripheral artery thrombosis); Severe, unhealed or dehisced wounds, as well as active ulcers or untreated fractures; Received major surgical treatment (except for diagnosis) within 4 weeks before the start of the study treatment or was expected to undergo major surgical treatment during the study period; 14.There is evidence suggesting the existence of intra-abdominal air accumulation that cannot be explained by puncture or recent surgical operations. 15.There has been or is currently metastasis to the central nervous system; Metastatic diseases involving major airways or blood vessels (for example, the main portal vein or vena cava that is completely occluded due to tumor invasion needs to be excluded from the group. The main portal vein refers to the confluence of the splenic vein and the superior mesenteric vein, as well as the branch where the hepatic portal vein divides into left and right branches) or large-volume mediastinal tumor masses located in the center (<30 mm from the protuberant spine); 16.Those with a history of hepatic encephalopathy; Those who are currently accompanied by interstitial pneumonia or interstitial lung disease, or have a previous history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, or other pulmonary fibrosis and organized pneumonia that may interfere with the judgment and management of immune-related pulmonary toxicity (for example, Subjects with oblusive bronchiolitis, pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or those who showed evidence of active pneumonia or severely impaired lung function on chest computed tomography (CT) images during the screening period were allowed to have radiation pneumonia in the radiation field. Active tuberculosis 17.Presence of active autoimmune diseases or a history of autoimmune diseases that may recur (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitinitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [subjects that can be controlled only through hormone replacement therapy can be included]); Subjects with skin diseases that do not require systemic treatment, such as vitiligo, psoriasis, alopecia, controlled type 1 diabetes treated with insulin, or asthma that has been completely relieved in childhood and does not require any intervention in adulthood can be included. Asthma patients who require medical intervention with bronchodilators cannot be included. 18. Use immunosuppressants or systemic hormone therapy within 14 days before the initiation of the study treatment to achieve the purpose of immunosuppression (dose >10 mg/ day prednisone or other therapeutic hormones); 19. A known history of severe allergy to any monoclonal antibody drug; 20. Those who are unable to swallow tablets normally or have abnormal gastrointestinal function, and the researcher determines that it may affect drug absorption; 21. There was a severe infection within 4 weeks before the initiation of the study treatment, including but not limited to hospitalization due to infection, bacteremia or complications of severe pneumonia; Therapeutic antibiotics were administered orally or intravenously within 2 weeks before the initiation of the study treatment (patients receiving preventive antibiotics (for example, those who are eligible to participate in the study to prevent urinary tract infections or exacerbation of chronic obstructive pulmonary disease); 22. Patients with congenital or acquired immune deficiency (such as HIV-infected individuals); 23. Co-infection with hepatitis B and hepatitis C; 24. Received attenuated live vaccine treatment within 28 days before the initiation of the study treatment, or is expected to be required to receive such vaccines during adbelimab treatment or within 60 days after the last administration of adbelimab; 25. According to the researcher's judgment, the patient has other factors that may affect the research results or lead to the forced termination of this study halfway, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, severe laboratory test abnormalities, accompanied by family or social factors, etc., which may affect the patient's safety.

研究实施时间：

Study execute time：

从 From 2024-10-11 00:00:00至 To 2027-04-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-10-11 00:00:00 至 To 2027-04-30 00:00:00

干预措施：

Interventions：

组别：

组1

样本量：

 30

Group：

Group 1

Sample size：

干预措施：

一个疗程的肝动脉灌注化疗，序贯一个疗程的静脉化疗

干预措施代码：

Intervention：

One course of hepatic arterial infusion chemotherapy, followed by a course of intravenous chemotherapy

Intervention code：

组别：

组2

样本量：

 30

Group：

Group 2

Sample size：

干预措施：

两个疗程的静脉化疗

干预措施代码：

Intervention：

Two courses of intravenous chemotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广西壮族自治区 

市(区县)：

 南宁 

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

Nanning

单位(医院)：

 南宁市第二人民医院 

单位级别：

 三甲 

Institution
hospital：

Nanning Second People's Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 广西壮族自治区 

市(区县)：

 南宁 

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

Nanning

单位(医院)：

 广西中医药大学第一附属医院 

单位级别：

 三甲 

Institution
hospital：

The First Affiliated Hospital of Guangxi University of Chinese Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

Objective response rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

6 个月无进展生存期率

指标类型：

次要指标

Outcome：

6-month progression-free survival 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：

疾病进展时间

指标类型：

次要指标

Outcome：

Disease progression time

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：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of remission

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：

评价阿得贝利单抗和安罗替尼联合肝动脉灌注化疗或静脉化疗用于晚期胆道肿瘤的一线治疗的安全性

指标类型：

次要指标

Outcome：

To evaluate adbelizumab and antilotinib combined with hepatic arterial infusion chemotherapy or intravenous infusion Safety of pulse chemotherapy for first-line treatment of advanced biliary tract tumors

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：

肿瘤组织

组织：

Sample Name：

Tumor tissue

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：

正在进行

Recruiting

年龄范围：

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

本研究为平行随机对照试验，签署知情同意书后进入筛选、满足入排标准的受试者接受阿得贝利单抗和安罗替尼联合治疗的基础上，将会通过随机系统按照 1:1 比例随机至队列 1（队列 1：一个疗程的肝动脉灌注化疗，序贯一个疗程的静脉化疗）或队列 2（两个疗程的静脉化疗）。随机化分层因素如下： 1. 病灶解剖位置（胆囊癌 vs 肝内胆管癌 vs 肝外胆管癌）； 2. 转移灶（有 vs 无）。

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

This study is a parallel randomized controlled trial. Subjects who enter the screening after signing informed consent and meet the admission criteria receive the combination therapy of adabiliumab and anlotinib, and will be randomly assigned to cohort 1 in a 1:1 ratio through a randomized system (Cohort 1: One course of hepatic arterial infusion chemotherapy followed by one course of intravenous chemotherapy) or Cohort 2 (two courses of intravenous chemotherapy). Randomized stratification factors were as follows: 1. Anatomic location of the lesion (gallbladder cancer vs. intrahepatic bile duct cancer vs. extrahepatic bile duct cancer); 2. Metastasis (yes vs no).

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）：

预计共享的时间2027年4月30日、通过邮件联系研究者

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

The expected sharing date is April 30, 2027, contact the researcher via email

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：

本课题设计有临床专用CRF表，专人进行纸质记录，保存于研究者处

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

Each patient are required to fill one CRF table, all the CRF tables saved by researchers

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：

  2025-05-13 14:50:06