ChiCTR2400092778 版本V1.0 版本创建时间2024/11/22 15:05:26 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：

ChiCTR2400092778 

最近更新日期：

Date of Last Refreshed on：

2024-11-22 15:05:09 

注册时间：

Date of Registration：

2024-11-22 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

替雷利珠单抗联合放疗在不可切除晚期或复发进展的原发性肝癌中的疗效与安全性研究

Public title：

Efficacy and safety of tislelizumab combined with radiotherapy in unresectable advanced or recurrent liver cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

替雷利珠单抗联合放疗在不可切除晚期或复发进展的原发性肝癌中的疗效与安全性研究

Scientific title：

Efficacy and safety of tislelizumab combined with radiotherapy in unresectable advanced or recurrent liver cancer

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：

孙寒 

研究负责人：

屈艳丽 

Applicant：

Sun Han 

Study leader：

Qu Yanli 

申请注册联系人电话：

Applicant telephone：

+86 191 0249 9013

研究负责人电话：

Study leader's telephone：

+86 189 0091 7260

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：

18840844914@163.com

研究负责人电子邮件：

Study leader's E-mail：

18840844914@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：

辽宁省沈阳市大东区小河沿路44号

研究负责人通讯地址：

辽宁省沈阳市大东区小河沿路44号

Applicant address：

No. 44, Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province

Study leader's address：

No. 44, Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province

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：

辽宁省肿瘤医院

Applicant's institution：

Liaoning Cancer Hospital & Institute

研究负责人所在单位：

辽宁省肿瘤医院

Affiliation of the Leader：

Liaoning Cancer Hospital & Institute

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：

20230351

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：

辽宁省肿瘤医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Liaoning Provincial Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2023-03-09 00:00:00

伦理委员会联系人：

李爽

Contact Name of the ethic committee：

Li Shuang

伦理委员会联系地址：

辽宁省沈阳市大东区小河沿路44号

Contact Address of the ethic committee：

No. 44, Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 24 8191 6631

伦理委员会联系人邮箱：

Contact email of the ethic committee：

lunlihuiyi@163.com

研究实施负责（组长）单位：

辽宁省肿瘤医院

Primary sponsor：

Liaoning Cancer Hospital & Institute

研究实施负责（组长）单位地址：

辽宁省沈阳市大东区小河沿路44号

Primary sponsor's address：

No. 44, Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

辽宁

市(区县)：

沈阳

Country：

China

Province：

Liaoning

City：

Shenyang

单位(医院)：

辽宁省肿瘤医院

具体地址：

辽宁省沈阳市大东区小河沿路44号

Institution
hospital：

Liaoning Cancer Hospital & Institute

Address：

No. 44, Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province

经费或物资来源：

百济神州（北京）生物科技有限公司

Source(s) of funding：

Beigene Biotechnology Co.

Target disease：

Liver Cancer

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

单臂 

Study design：

Single arm 

研究目的：

通过单中心、前瞻性临床试验，观察替雷利珠单抗联合放射治疗在不可切除晚期或复发进展的原发性肝癌中的疗效与安全性研究。  

Objectives of Study：

To investigate the efficacy and safety of tirelizumab combined with radiation therapy in primary, unresectable advanced or recurrent liver cancer in a single-center, prospective clinical trial

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.同意并能够签署书面知情同意书。 2.签署知情同意书当天年龄≥18岁且≤75岁。 3.局部晚期肝细胞肝癌，经组织学/细胞学、影像学（增强MRI或增强CT或PET-CT）肝细胞癌的临床诊断标准。 4.无共同或主要分支胆管侵犯的证据。 5.既往接受过其他局部治疗（如手术切除、介入治疗、消融治疗、无水酒精注射、氩氦刀治疗等）或系统性抗肿瘤治疗后发生疾病进展的患者可以纳入本研究。 6.患者肝脏病灶及门静脉癌栓病灶可行放疗。 7.拟接受放疗的肝内病灶没有直接的肿瘤侵犯到胃，十二指肠，小肠，大肠或膈肌的证据，且距离胃肠道存在合适的安全距离。 8.肝内病灶相对局限，肝脏肿瘤小于60%肝体积，能够涵盖在同一靶区内，且放疗靶区以外的剩余肝脏体积应大于700ml。 9.肝功能符合Child Pugh A级（评分为5-6分）。 10.东部肿瘤协作组（ECOG）的一般状态评分为0或1分。 11.入组前须进行乙肝表面抗原检测，对于确定有乙型肝炎的患者，应在放疗前1周开始应用抗病毒药物。 12.在研究筛查期间，必须对患者进行丙型肝炎病毒（HCV）RNA状态的检测。本研究允许未经治疗的慢性HCV感染患者进行研究。此外，对于丙肝治愈的患者，可纳入本研究，但入组时丙肝治疗应结束4周以上。 13.主要器官功能基本正常，符合下列要求：骨髓：中性粒细胞绝对计数≥1.5×109/L，血小板≥50×10^9/L，血红蛋白≥90g/L。肝脏：总胆红素≤2倍正常值上限（ULN），天冬氨酸转氨酶和丙氨酸转氨酶≤5×ULN，白蛋白≥29g/L。肾脏：血清肌酐≤1.5×ULN，或肌酐清除率≥50mL/min。凝血功能：国际标准化比率（INR）≤ 2，且活化部分凝血活酶时间（APTT）≤ 1.5倍ULN。 14.预期生存＞3个月。 15.育龄妇女必须同意在研究入组前，研究参与期间以及最后一次研究药物治疗后至少30天内使用有效的避孕方法。育龄妇女需要在开始治疗前72小时内进行血清妊娠试验。治疗或登记此试验的男性必须同意在完成PD-1抑制剂治疗前和治疗4个月后使用适当的避孕措施。 16.筛选前4周内未参加其他临床试验；如果其他试验筛选失败病例，但是符合本试验要求者可以入组。

Inclusion criteria

1.Patients should sign informed consent before beginning any treatment. Patients must understand and voluntarily sign a written informed consent. 2.Age 18 to 75 years. 3.Locally advanced hepatocellular carcinoma diagnosed by clinical diagnostic criteria by cytology, histology, or clinical diagnosis by CT, MRI and laboratory examinations (MRI, CT or PET-CT). 4.There was no evidence of common or major branching bile duct invasion. 5.Patients with disease progression after previous other local treatments (e.g., surgery, interventional therapy, ablative therapy, argon helium knife therapy, etc.) or systemic therapy can be included in this study. 6.Radiotherapy is feasible for the patient's liver lesions and portal vein tumor thrombus lesions. 7.The intrahepatic lesions to be radiated had no evidence of direct tumor invasion into the stomach, duodenum, small intestine, large intestine, or diaphragm, and a suitable safe distance from the gastrointestinal tract. 8.The intrahepatic lesion is relatively confined, the liver tumor is less than 60% of the liver volume, it is able to encompass the same target area, and the remaining liver volume outside the radiotherapy target area should be greater than 700 ml. 9.Child-Pugh grade A. 10.Eastern Cooperative Oncology Group (ECOG) score was≤1. 11.Hepatitis B surface antigen test should be performed before enrollment, and antiviral drugs should be started 1 week before radiotherapy for patients who are determined to have hepatitis B. 12.During study screening, patients must be tested for hepatitis C virus (HCV) RNA status. Patients with untreated chronic HCV infection are allowed in this study. In addition, patients who are cured of hepatitis C may be enrolled in this study, but hepatitis C treatment should have been completed for more than 4 weeks at the time of enrollment. 13.No significant abnormalities in organ and bone marrow function. Platelet count >= 50×10^9/L, neutrophil absolute value >= 1.5×10^9/L, Hemoglobin≥90g/L; Total bilirubin <= 2×ULN, aspartate aminotransferase <= 5×ULN, alanine aminotransferase <= 5×ULN, Albumin >= 29g / L.serum creatinine <1.5×ULN, estimated glomerular filtration rate >= 50mL/min. International normalized ratio (INR) <= 2, activated partial thromboplastin time (APTT) <= 1.5×ULN. 14.The expected survival is not less than 3 months. 15.Women of childbearing potential must agree to use an effective method of contraception for at least 30 days prior to study enrollment, during study participation, and for at least 30 days after the last study drug treatment. Women of childbearing potential will be required to undergo a serum pregnancy test within 72 hours prior to initiating treatment. Men treated or enrolled in this trial must agree to use appropriate contraception prior to completion of PD-1 inhibitor treatment and 4 months after treatment. 16.Patients are not enrolled in another clinical trial within 4 weeks prior to screening; if a case fails screening in another trial but meets the requirements of this trial may be enrolled.

排除标准：

1.先前已对拟治疗区域进行过放疗。 2.存在肝外转移的患者。 3.癌栓侵犯至肠系膜上静脉的患者。 4.存在下腔静脉癌栓的患者。 5.目前正在参与并接受其他实验性治疗，或者参加了免疫检查点抑制剂研究并接受了研究治疗。 6.先前曾进行实体器官移植，诊断为免疫缺陷，或在首次试验治疗前7天内接受全身性类固醇治疗或任何其他形式的免疫抑制治疗。 7.肝肿瘤不适合放射治疗，或者之前有上腹部放射治疗病史，肝脏受到射线照射。 8.有纤维片状HCC，肉瘤样HCC或混合胆管癌-HCC的组织学或细胞学诊断。 9.先前已对肝脏进行放射栓塞或其他选择性内部放疗。 10.入组前3个月内曾有食道或胃底静脉曲张出血。 11.在过去的6个月中有过肝性脑病，或者在入选时有明显的腹水。 12.有已知的活动性结核病病史。 13.对PD-1抑制剂过敏。 14.受试者同时具有其他已知的侵袭性恶性肿瘤（通过治疗目前没有肿瘤复发的证据，且持续时间在2年以上者除外）。例外情况包括：皮肤基底细胞癌，皮肤鳞状细胞癌，浅表性膀胱癌，低风险前列腺癌或原位宫颈癌。 15.既往有需要全身治疗的活动性自身免疫性疾病的患者。 16.已知有活动的非感染性肺炎的病史或任何证据。 17.有活动性感染需要全身治疗。 18.有已知的精神疾病或药物滥用障碍者。 19.妊娠或哺乳期女性。 20.先前接受过抗PD-1，抗PD-L1药物的治疗者需停药时间短于6个月。 21.有已知的人类免疫缺陷病毒（HIV）病史（HIV 1/2抗体）。 22.计划开始研究治疗前30天内接种过活疫苗。 23.患有高血压，且经降压药物治疗无法获得良好控制者（收缩压>140mmHg，舒张压>100mmHg）；患有CTCAE分级Ⅱ级以上心肌缺血或心肌梗塞、控制不良的心律失常，和/或纽约心脏协会（NYHA）Ⅲ~Ⅳ级的心功能不全。 24.各种原因导致的无法平卧或无法长时间平卧的患者。 25.1.研究者认为妨碍患者参加本试验的其他状况。

Exclusion criteria：

1.Radiotherapy has previously been given to the proposed treatment area. 2.Patients with extrahepatic metastases. 3.Patients with cancerous thrombus invading the superior mesenteric vein. 4.Patients with cancerous thrombus invading inferior vena cava. 5.Patients are currently participating in and receiving other experimental treatments, or participating in an immune checkpoint inhibitor study and receiving investigational treatment. 6.Patients who had been transplantated solid organ diagnosed as immunodeficiency. Patients received systemic steroid therapy or any other immunosuppressive therapy within 7 days before the first trial treatment. 7.The liver tumor is not suitable for radiotherapy. There is a previous history of upper abdominal radiotherapy and radiation irradiation of the liver. 8.Patients had a histologic or cytologic diagnosis of fibrous sheet HCC, sarcomatoid HCC, or mixed cholangiocarcinoma-HCC. 9.Radiation embolization or other selective internal radiotherapy to the liver has been performed. 10.Patiens had bleeding from esophageal or fundal varices within 3 months pre-entry. 11.Patients had hepatic encephalopathy in the past 6 months or significant ascites at enrollment. 12.Patients have active tuberculosis. 13.Patient are allergic to PD-1 inhibitors. 14.The patient has other known aggressive malignancies at the same time (except for those who have no current evidence of tumor recurrence with treatment that has lasted more than 2 years). Exceptions include: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, low-risk prostate cancer, or cervical cancer in situ. 15.Patients have prior active autoimmune disease requiring systemic therapy. 16.Patients have active uninfectious pneumonia. 17.Patients who have active infection are required systemic therapy. 18.Patients have known mental illness or substance abuse disorder. 19.Women who are pregnant or breastfeeding. 20.Patients who have treatment with anti-PD-1, anti-PD-L1 drugs must have been discontinued for less than 6 months. 21.Patients had history of human immunodeficiency virus (HIV) (HIV 1/2 antibody). 22.Patients have received vaccine within 30 days prior to the planned start of study treatment. 23.Patients have hypertension that is not well controlled by antihypertensive medications (systolic blood pressure > 140 mmHg, diastolic blood pressure > 100 mmHg); myocardial ischemia or myocardial infarction of CTCAE Class II or higher, poorly controlled arrhythmia, and/or New York Heart Association (NYHA) Class III-IV cardiac insufficiency. 24. Patients who are unable to lie flat or for prolonged periods of time for various reasons. 25.Other conditions that the investigator considered prevent the patient's participation in the trial.

研究实施时间：

Study execute time：

从 From 2023-01-01 00:00:00至 To 2026-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-11-10 00:00:00 至 To 2026-12-31 00:00:00  

干预措施：

Interventions：

组别：

治疗组

样本量：

30

Group：

Treatment group

Sample size：

干预措施：

放射治疗联合替雷利珠单抗免疫治疗

干预措施代码：

Intervention：

Radiotherapy with Tislelizumab Injection.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 辽宁省 

市(区县)：

 沈阳 

Country：

China 

Province：

Liaoning 

City：

Shenyang 

单位(医院)：

辽宁省肿瘤医院 

单位级别：

三甲 

Institution
hospital：

Liaoning Cancer Hospital & Institute

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

不良事件

指标类型：

主要指标

Outcome：

Adverse event

Type：

Primary 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 remission 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：

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：

无进展生存期

指标类型：

次要指标

Outcome：

Progression free 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：

缓解持续时间

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：

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：

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

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）：

研究论文发表后，通过向研究者申请可以获得研究数据共享。

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

After the research paper is published, the research data can be shared by applying to the researcher.

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：

数据采集使用人工填写病例记录表。数据录入使用Excel和SPSS进行录入和数据管理。

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

The data were collected by manually filling out the case record form. Data entry Excel and SPSS were used for data entry and data management.

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：

  2024-11-22 15:05:09