ChiCTR2600120479 版本V1.0 版本创建时间2026/03/16 10:32:49 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：

ChiCTR2600120479 

最近更新日期：

Date of Last Refreshed on：

2026-03-16 10:32:30 

注册时间：

Date of Registration：

2026-03-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

QL1706 联合多纳非尼及肝动脉灌注化疗（HAIC）一线治疗不可切除胆道恶性肿瘤的单臂、II 期临床研究

Public title：

A Single arm, phase II clinical study of QL1706 combined with Donafenib and hepatic arterial infusion chemotherapy (HAIC) as first-line treatment for unresectable biliary malignant tumors

注册题目简写：

English Acronym：

研究课题的正式科学名称：

QL1706 联合多纳非尼及肝动脉灌注化疗（HAIC）一线治疗不可切除胆道恶性肿瘤的单臂、II 期临床研究

Scientific title：

A Single arm, phase II clinical study of QL1706 combined with Donafenib and hepatic arterial infusion chemotherapy (HAIC) as first-line treatment for unresectable biliary malignant tumors

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：

郝明志 

研究负责人：

郝明志 

Applicant：

Mingzhi Hao 

Study leader：

Mingzhi Hao 

申请注册联系人电话：

Applicant telephone：

+86 130 6723 1562

研究负责人电话：

Study leader's telephone：

+86 130 6723 1562

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：

1196819910@qq.com

研究负责人电子邮件：

Study leader's E-mail：

1196819910@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：

福州市福马路420号

研究负责人通讯地址：

福州市福马路420号

Applicant address：

No. 420, Fuma Road, Fuzhou City

Study leader's address：

No. 420, Fuma Road, Fuzhou City

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：

福建省肿瘤医院

Applicant's institution：

Fujian Cancer Hospital

研究负责人所在单位：

福建省肿瘤医院

Affiliation of the Leader：

Fujian Cancer 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：

K2025-310-01

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：

福建省肿瘤医院科研及新技术伦理委员会

Name of the ethic committee：

Fujian Provincial Tumor Hospital Research and New Technology Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2025-08-29 00:00:00

伦理委员会联系人：

余文昌

Contact Name of the ethic committee：

Wenchang Yu

伦理委员会联系地址：

福州市福马路420号

Contact Address of the ethic committee：

No. 420, Fuma Road, Fuzhou City

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 591 6275 6181

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：

福建省肿瘤医院

Primary sponsor：

Fujian Cancer Hospital

研究实施负责（组长）单位地址：

福州市福马路420号

Primary sponsor's address：

No. 420, Fuma Road, Fuzhou City

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

福建

市(区县)：

福州

Country：

China

Province：

Fujian

City：

Fuzhou

单位(医院)：

福建省肿瘤医院

具体地址：

福州市福马路420号

Institution
hospital：

Fujian Cancer Hospital

Address：

No. 420, Fuma Road, Fuzhou City

经费或物资来源：

自筹

Source(s) of funding：

Self-financed

Target disease：

Inoperable malignant biliary tumors

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QL1706联合多纳非尼及肝动脉灌注化疗（HAIC）一线治疗不可切除胆道恶性肿瘤的有效性和安全性  

Objectives of Study：

Evaluation of the efficacy and safety of QL1706 combined with Donafenib and hepatic arterial infusion chemotherapy (HAIC) as first-line treatment for unresectable biliary malignancies

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.年龄18-75岁； 2.经病理组织/细胞学确诊的不可手术切除的胆道恶性肿瘤，包括肝内胆管癌、肝外胆管癌及胆囊癌； 3.ECOG PS评分≤1分； 4.根据RECIST 1.1评估标准至少有一个可测量病灶； 5.既往未接受过系统（如靶向、免疫、化疗）或局部（如HAIC、TACE）抗肿瘤治疗，手术切除、放疗和消融除外； 6.Child-Pugh 肝功能评分≤7 分； 7.无HAIC、靶向药物及免疫治疗禁忌； 8.足够的血液学和器官功能，入组治疗前 14 天内需符合以下标准（在获得检查结果的前 14 天内，不允许通过静脉或皮下给药的血液成分、细胞生长因子、白蛋白和其他药物进行矫正治疗）： - 中性粒细胞计数≥1.5 x 10^9/L，血小板≥75 x 10^9/L，血红蛋白≥90 g/L； - 血清肌酐≤1.5 x 正常值上限（ULN），肌酐清除率≥50 mL/min（Cockcroft-Gault 公式）； - 丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）≤3×ULN（肝转移患者为 ≤5×ULN），总胆红素 （BIL） ≤2×ULN（吉尔伯特综合征患者为 ≤3×ULN）； - 国际标准化比值（INR）或活化部分凝血活酶时间（APTT）≤1.5 x ULN（对于在研究治疗前 14 天内接受预防性抗凝治疗的患者，INR≤2 x ULN，APTT在正常范围内）； - 心脏功能正常，二维超声心动图测量左心室射血分数（LVEF）≥ 20%； 9.预期寿命＞3个月； 10.育龄期妇女受试者必须在入组前7天内进行血清妊娠试验，结果为阴性，且同意在试验期间和末次给药后3个月内采用可靠有效的方法避孕。对于伴侣为育龄期妇女的男性受试者，必须同意在试验期间和末次给药后3个月内采用可靠有效的方法避孕。哺乳期妇女不能入组； 11.受试者须在试验前对本研究知情同意，并自愿签署书面的知情同意书，愿意并能够遵守研究计划的访视、治疗计划、实验室检查和其他研究程序。

Inclusion criteria

1. Age range: 18-75 years old 2. Non resectable malignant tumors of the biliary tract, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, diagnosed by pathological organization/cytology; 3. ECOG PS score <= 1 point; 4. According to RECIST 1.1 evaluation criteria, there must be at least one measurable lesion; 5. Have not received systemic (such as targeted, immune, chemotherapy) or local (such as HAIC, TACE) anti-tumor treatment in the past, except for surgical resection, radiotherapy, and ablation; 6. Child Pugh liver function score <= 7 points; 7. No contraindications for HAIC, targeted drugs, or immunotherapy; 8. Adequate hematology and organ function must meet the following criteria within 14 days prior to enrollment in treatment (within 14 days prior to obtaining test results, corrective treatment with blood components, cell growth factors, albumin, and other drugs administered intravenously or subcutaneously is not allowed): -Neutrophil count >= 1.5 x 10^9/L, platelets >= 75 x 10^9/L, hemoglobin >= 90 g/L; -Serum creatinine <= 1.5 x upper limit of normal (ULN), creatinine clearance rate >= 50 mL/min (Cockcroft Gault formula); -Alanine transaminase (ALT) and aspartate transaminase (AST) <= 3 × ULN (<= 5 × ULN in patients with liver metastases), total bilirubin (BIL) <= 2 × ULN (<= 3 × ULN in patients with Gilbert syndrome); -International normalized ratio (INR) or activated partial thromboplastin time (APTT) <= 1.5 x ULN (for patients receiving prophylactic anticoagulant therapy within 14 days prior to study treatment, INR <= 2 x ULN and APTT within normal range); -The heart function is normal, and the left ventricular ejection fraction (LVEF) measured by two-dimensional echocardiography is >= 20%; 9. Expected lifespan>3 months; 10. Women of childbearing age must undergo a serum pregnancy test within 7 days before enrollment, with a negative result, and agree to use reliable and effective contraception methods during the trial period and for 3 months after the last dose. For male participants whose partners are women of childbearing age, they must agree to use reliable and effective methods of contraception during the trial period and within 3 months after the last dose. Breastfeeding women cannot be included in the group; 11. Participants must give informed consent to this study prior to the trial and voluntarily sign a written informed consent form. They are willing and able to comply with the visit, treatment plan, laboratory tests, and other research procedures outlined in the study plan.

排除标准：

1.经组织学或细胞学证实的罕见组织病理学类型的胆管癌，如壶腹癌、小细胞癌、神经内分泌肿瘤、肉瘤和粘液性囊性肿瘤； 2.既往或计划进行任何器官移植； 3.未如预期减轻黄疸的阻塞性黄疸患者； 4.入组前 5 年内患有其他恶性肿瘤的受试者，已治愈的皮肤基底细胞癌或宫颈原位癌除外； 5.确诊或疑似有症状的活动性脑或脑膜转移患者； 6.在过去 3 个月内或计划在研究期间参加过另一项干预性临床研究，或同时参加过另一项临床研究，除非是观察性、非干预性研究或干预性研究的随访期； 7.研究者认为受试者不适合入组的其他疾病证据，例如未控制的高血压、活动性出血性疾病、活动性感染或不受控制的感染（≥CTCAE 2 级感染）、活动性间质性肺病、与腹泻相关的严重慢性胃肠道疾病、精神疾病或社会状况，或同种异体器官移植史； 8.严重心血管疾病史：给药前12个月内NYHA II级或以上心力衰竭、不稳定型心绞痛、心肌梗塞、不受控制的心律失常或脑血管意外;超声心动图显示 LVEF <50%;QTc >480ms（Fridericia 方法，如果 QTc 异常，则间隔 2 分钟连续三次测量的平均值）;高血压控制不佳（收缩压 ≥150 mmHg 和/或舒张压 ≥100 mmHg，基于 ≥2 测量值的平均值）;高血压危象或脑病病史； 9.活动性原发性免疫缺陷病史或人类免疫缺陷病毒病史;过去 2 年内患有活动性自身免疫性疾病或可能复发的自身免疫性疾病病史，包括但不限于自身免疫性肝炎、间质性肺炎、葡萄膜炎、结肠炎、垂体炎、血管炎、肾炎、甲状腺功能亢进症、甲状腺功能减退症（不包括接受激素替代疗法控制的患者）； 10.既往免疫治疗，包括免疫检查点抑制剂（例如，抗 PD-1/L1、CTLA-4、TIGIT、LAG3 抗体）、免疫检查点激动剂（例如，CD40、CD137、OX40 抗体）或其他针对肿瘤免疫机制的免疫疗法，治疗性抗肿瘤疫苗除外； 11.目前正在使用或在研究药物首次给药前 14 天内使用过免疫抑制药物。 以下情况除外：（1）鼻内、吸入、局部或局部类固醇（例如，关节内）；（2）全身性皮质类固醇治疗不超过 10 毫克/天的泼尼松；（3）预防性使用类固醇治疗超敏反应（例如，CT 扫描治疗前用药）； 12.在研究药物首次给药前 30 天内接种了减毒活疫苗。 注意：如果入组，患者在接受研究药物治疗后 30 天内和最后一次服用研究药物后不得接种减毒活疫苗； 13.HBV（HBsAg 和/或抗 HBcAb 阳性，可检测到 HBV DNA）和 HCV（抗 HCV 抗体阳性）或 HBV 和 HDV（抗 HDV 抗体阳性）的混合感染； 14.首次给药前 6 个月内严重消化性溃疡、胃炎、胃肠道穿孔、腹瘘、梗阻、腹腔内脓肿或急性胃肠道出血;首次给药前 1 个月内 COPD 急性加重； 15.首次研究药物给药前 3 个月内发生明显出血倾向证据或病史（包括呕血、便血、咯血）;需要输血、手术、局部治疗或持续药物治疗的出血事件；有遗传性或获得性出血或凝血病病史的患者；在随访研究期间，肿瘤被研究者判断为极易侵犯重要血管并导致致命出血的患者； 16.首次给药前 30 天内进行过大手术或严重创伤，或首次给药后 30 天内计划进行过大手术（研究者决定）;首次给药前 3 天内进行过局部小手术（不包括中心静脉导管放置和静脉端口植入）； 17.孕妇或哺乳期妇女;从筛选到最后一次研究干预剂量后 90 天或最后一次研究药物剂量后 180 天，不愿使用有效避孕措施的具有生育潜力的男性或女性； 18.已知对任何研究药物或其赋形剂过敏或超敏反应； 19.存在其他可能影响研究结果或导致强制终止研究的因素，如酗酒、滥用药物、其他需要联合治疗的严重疾病（包括精神疾病），或其他研究者认为不适合纳入的因素。

Exclusion criteria：

1. Rare histopathological types of cholangiocarcinoma confirmed by histology or cytology, such as ampulla carcinoma, small cell carcinoma, neuroendocrine tumor, sarcoma, and mucinous cystic tumor 2. Any previous or planned organ transplant; 3. Obstructive jaundice patients who did not experience the expected reduction in jaundice; 4. Subjects with other malignant tumors within the 5 years prior to enrollment, except for cured skin basal cell carcinoma or cervical carcinoma in situ; 5. Diagnosed or suspected symptomatic patients with active brain or meningeal metastases; 6. Have participated in another interventional clinical study within the past 3 months or planned to participate in another clinical study during the study period, or have participated in another clinical study simultaneously, unless it is an observational, non interventional study, or a follow-up period of an interventional study; 7. Evidence of other diseases that the researcher considers unsuitable for inclusion in the study, such as uncontrolled hypertension, active hemorrhagic disease, active or uncontrolled infection (>= CTCAE level 2 infection), active interstitial lung disease, severe chronic gastrointestinal disease associated with diarrhea, mental illness or social condition, or history of allogeneic organ transplantation; 8. History of severe cardiovascular disease: NYHA class II or above heart failure, unstable angina, myocardial infarction, uncontrolled arrhythmia, or cerebrovascular accident within 12 months prior to administration; Echocardiography shows LVEF<50%; QTc >480ms (Fridericia method, if QTc is abnormal, the average of three consecutive measurements taken every 2 minutes); Poor control of hypertension (systolic blood pressure >= 150 mmHg and/or diastolic blood pressure >= 100 mmHg, based on the average of >= 2 measurements); History of hypertensive crisis or encephalopathy; 9. History of active primary immunodeficiency or human immunodeficiency virus; History of active autoimmune diseases or potential recurrence of autoimmune diseases within the past 2 years, including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism (excluding patients controlled by hormone replacement therapy); 10: Previous immunotherapy, including immune checkpoint inhibitors (such as anti-PD-1/L1, CTLA-4, TIGIT, LAG3 antibodies), immune checkpoint agonists (such as CD40, CD137, OX40 antibodies), or other immunotherapy targeting tumor immune mechanisms, in addition to therapeutic anti-tumor vaccines; 11. Currently using or having used immunosuppressive drugs within 14 days prior to the first administration of the investigational drug. Except for the following situations: (1) intranasal, inhaled, local, or topical steroids (e.g. intra-articular); (2) Systemic corticosteroid treatment with prednisone not exceeding 10 milligrams per day; (3) Prophylactic use of steroids to treat hypersensitivity reactions (e.g. medication before CT scan treatment); 12. Received attenuated live vaccine within 30 days prior to the first administration of the investigational drug. Attention: If enrolled, patients are not allowed to receive attenuated live vaccines within 30 days after receiving study drug treatment and after the last dose of study drug; 13. Mixed infection of HBV (HBsAg and/or anti HBcAb positive, detectable HBV DNA) and HCV (anti HCV antibody positive) or HBV and HDV (anti HDV antibody positive); 14. Severe peptic ulcer, gastritis, gastrointestinal perforation, abdominal fistula, obstruction, intra-abdominal abscess or acute gastrointestinal bleeding within 6 months before the first administration; Acute exacerbation of COPD within one month prior to the first administration; 15. Evidence or medical history of obvious bleeding tendency (including vomiting blood, rectal bleeding, hemoptysis) within 3 months before the first drug administration in the study; Bleeding events that require blood transfusion, surgery, local treatment, or continuous medication therapy; Patients with a history of hereditary or acquired bleeding or coagulation disorders; During the follow-up study, the tumor was identified by the researchers as a patient who is highly susceptible to invading important blood vessels and causing fatal bleeding; 16. If a major surgery or severe trauma has been performed within 30 days prior to the first administration, or if a major surgery is planned within 30 days after the first administration (as determined by the investigator); Local minor surgery (excluding central venous catheter placement and venous port implantation) performed within 3 days prior to the first administration; 17. Pregnant or lactating women; Men or women with reproductive potential who are unwilling to use effective contraceptive measures from screening to 90 days after the last intervention dose or 180 days after the last study drug dose; 18. Known allergies or hypersensitivity reactions to any investigational drug or its excipients; 19. There are other factors that may affect the research results or lead to forced termination of the study, such as alcohol abuse, drug abuse, other serious illnesses that require combination therapy (including mental illness), or other factors that the researcher deems unsuitable for inclusion.

研究实施时间：

Study execute time：

从 From 2026-03-16 00:00:00至 To 2028-03-13 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2026-03-16 00:00:00 至 To 2028-03-13 00:00:00  

干预措施：

Interventions：

组别：

治疗组

样本量：

32

Group：

treatment group

Sample size：

干预措施：

QL1706联合多纳非尼及肝动脉灌注化疗

干预措施代码：

Intervention：

QL1706 combined with Donafenib and hepatic arterial infusion chemotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 福建 

市(区县)：

 福州 

Country：

China 

Province：

Fujian 

City：

Fuzhou 

单位(医院)：

福建省肿瘤医院 

单位级别：

三甲 

Institution
hospital：

Fujian Cancer Hospital

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, ORR

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无疾病进展生存期

指标类型：

次要指标

Outcome：

Progression-Free Survival, PFS

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, DCR

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, 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：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of Overall Response, DoR

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：

病理活检标本

组织：

Sample Name：

Pathological biopsy specimens

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：

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:

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

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）：

如对原始数据有合理需求者，可与项目负责人联系

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

The way of sharing IPD: Contact with PI if reasonable request on raw data is met.

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：

Case Record Form, 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：

  2026-03-16 10:32:30