简体中文|English
Trial search Nation, Province(City) Code of disease Primary sponsor(s) Secondary sponsor(s) Funding source Recruiting status Register status Measure Ethical committee Study type

Efficacy and safety of spatially fractionated radiotherapy combined with immune checkpoint inhibitors and anti-angiogenic targeted agents as later-line treatment for bulky hepatobiliary tumors

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注册号：

Registration number：

ChiCTR2600124765 

最近更新日期：

Date of Last Refreshed on：

2026-05-17 19:57:59 

注册时间：

Date of Registration：

2026-05-17 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

空间分割放疗联合免疫检查点抑制剂和抗血管生成靶向药物后线治疗伴有大肿块肝胆肿瘤的有效性和安全性研究

Public title：

Efficacy and safety of spatially fractionated radiotherapy combined with immune checkpoint inhibitors and anti-angiogenic targeted agents as later-line treatment for bulky hepatobiliary tumors

注册题目简写：

English Acronym：

研究课题的正式科学名称：

空间分割放疗联合免疫检查点抑制剂和抗血管生成靶向药物后线治疗伴有大肿块肝胆肿瘤的有效性和安全性研究

Scientific title：

Efficacy and safety of spatially fractionated radiotherapy combined with immune checkpoint inhibitors and anti-angiogenic targeted agents as later-line treatment for bulky hepatobiliary 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：

李丽 

研究负责人：

李丽 

Applicant：

Li Li 

Study leader：

Li Li 

申请注册联系人电话：

Applicant telephone：

+86 18661806632

研究负责人电话：

Study leader's telephone：

+86 10 69007647

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：

lili1@pkuih.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

lili1@pkuih.edu.cn

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：

中国北京市昌平区生命科学园路1号

研究负责人通讯地址：

中国北京市昌平区生命科学园路1号

Applicant address：

1 Life Science Park Road, Changping District, Beijing, China

Study leader's address：

1 Life Science Park Road, Changping District, Beijing, 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：

北京大学国际医院

Applicant's institution：

Peking University International Hospital

研究负责人所在单位：

北京大学国际医院

Affiliation of the Leader：

Peking University International 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：

2026-KY-0042-01

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：

北京大学国际医院生物医学伦理委员会

Name of the ethic committee：

Peking University International Hospital Institutional Review Board

伦理委员会批准日期：

Date of approved by ethic committee：

2026-03-26 00:00:00

伦理委员会联系人：

赵俊

Contact Name of the ethic committee：

Zhao Jun

伦理委员会联系地址：

中国北京市昌平区生命科学园路1号

Contact Address of the ethic committee：

1 Life Science Park Road, Changping District, Beijing, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 10 69007608

伦理委员会联系人邮箱：

Contact email of the ethic committee：

zhaojun@pkuih.edu.cn

研究实施负责（组长）单位：

北京大学国际医院

Primary sponsor：

Peking University International Hospital

研究实施负责（组长）单位地址：

中国北京市昌平区生命科学园路1号

Primary sponsor's address：

1 Life Science Park Road, Changping District, Beijing, 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)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

北京大学国际医院

具体地址：

中国北京市昌平区生命科学园路1号

Institution
hospital：

Peking University International Hospital

Address：

1 Life Science Park Road, Changping District, Beijing, China

经费或物资来源：

自筹

Source(s) of funding：

Self-funded

Target disease：

Histologically confirmed advanced hepatocellular carcinoma or biliary tract malignancies (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) that have failed at least one line of prior systemic therapy; presence of >=2 tumor lesions, including a bulky tumor with a short diameter of >=5 cm that is assessed as suitable for spatially fractionated radioth

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：

聚焦晚期肝胆肿瘤的后线治疗困境，探索SFRT联合免疫检查点抑制剂和抗血管生成靶向药物，在克服耐药、诱导远隔效应、以及提升疾病整体控制方面的积极作用。并通过对血液标本的免疫指标进行动态监测，分析治疗对全身免疫应答的影响、以及免疫微环境的多维度动态变化与疗效相关性，为理解相关效应机制和临床个体化治疗患者提供线索。  

Objectives of Study：

Focusing on the dilemma of later-line treatment for advanced hepatobiliary tumors, this study explores the positive effects of combining SFRT with immune checkpoint inhibitors and anti-angiogenic targeted agents in overcoming drug resistance, inducing abscopal effects, and improving overall disease control. Furthermore, through dynamic monitoring of immune markers in blood samples, it analyzes the impact of treatment on systemic immune responses and the correlation between multi-dimensional dynamic changes in the immune microenvironment and treatment efficacy, thereby providing clues for understanding the underlying mechanisms and guiding individualized clinical treatment for patients.

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. 入组前签署书面知情同意书； 2. 年龄>18岁，男女均可； 3. 组织或病理学确诊的晚期肝细胞癌或胆道系统恶性肿瘤（包括肝内胆管细胞癌、肝外胆管细胞癌和胆囊癌）； 4. 既往接受过系统治疗后进展/不耐受； 5. 具有放疗野外的可测量的病灶（RECIST 1.1标准）； 6. 具有短径>=5cm研究者评估可行空间分割放疗的病灶； 7. ECOG PS评分：0-2； 8. 预期生存期大于12周； 9. 常规化验符合下列要求（不包括14天内用任何血液成分及细胞生长因子）： (1) 血常规：中性粒细胞>=1.5×10^9/L；血小板计数>=75×10^9/L；血红蛋白>=80g/L； (2) 肝肾功能：血清肌酐(SCr)<=1.5倍正常值上限（ULN）或肌酐清除率>=50 ml/min（Cockcroft-Gault公式）；总胆红素（TBIL）<=2倍正常值上限（ULN）；谷草转氨酶（AST）或谷丙转氨酶（ALT）水平<=3倍正常值上限（ULN）； (3) 尿液分析：尿蛋白<2+；如果尿蛋白>=2+，则24小时尿蛋白定量显示蛋白质<=1g； 10. 凝血功能正常，无活动性出血和血栓形成疾病： (1) 国际标准化比值INR<=1.5×ULN； (2) 部分凝血活酶时间APTT<=1.5×ULN； (3) 凝血酶原时间PT<=1.5×ULN； 11. 非手术绝育或育龄期女性患者，需要在研究治疗期间和研究治疗期结束后3个月内采用一种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套）；非手术绝育的育龄期女性患者在研究入组前的7天内血清或尿HCG检查必须为阴性；而且必须为非哺乳期；非手术绝育或育龄期男性患者，需要同意与其配偶在研究治疗期间和研究治疗期结束后3个月内采用一种经医学认可的避孕措施； 12. 受试者自愿加入本研究，依从性好，配合安全性和生存期随访。

Inclusion criteria

1. Provide written informed consent prior to enrollment. 2. Age >18 years, male or female. 3. Histologically or pathologically confirmed advanced hepatocellular carcinoma or biliary tract malignancies (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer). 4. Progression or intolerance after prior systemic therapy. 5. Presence of measurable lesions outside the radiotherapy field (RECIST 1.1 criteria). 6. Presence of a lesion with a short diameter >=5 cm assessed by the investigator as suitable for spatially fractionated radiotherapy (SFRT). 7. ECOG performance status score: 0-2. 8. Life expectancy >12 weeks. 9. Routine laboratory tests meeting the following requirements (without any blood product or cell growth factor transfusion within 14 days): (1) Complete blood count: neutrophil count >=1.5x10^9/L; platelet count >=75x10^9/L; hemoglobin >=80 g/L. (2) Liver and kidney function: serum creatinine (SCr) <=1.5x upper limit of normal (ULN) or creatinine clearance >=50 mL/min (Cockcroft Gault formula); total bilirubin (TBIL) <=2xULN; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels <=3xULN. (3) Urinalysis: urine protein <2+; if urine protein >=2+, then 24 hour urine protein quantification shows protein <=1 g. 10. Normal coagulation function, no active bleeding or thromboembolic disease: (1) International normalized ratio (INR) <=1.5xULN. (2) Activated partial thromboplastin time (APTT) <=1.5xULN. (3) Prothrombin time (PT) <=1.5xULN. 11. For female patients of childbearing potential (non surgically sterilized): must agree to use a medically approved contraceptive method (e.g., intrauterine device, oral contraceptive, or condom) during the study treatment period and for 3 months after the end of treatment; have a negative serum or urine HCG test within 7 days prior to enrollment; and must not be breastfeeding. For male patients (non surgically sterilized or of childbearing potential): must agree to use a medically approved contraceptive method with their partner during the study treatment period and for 3 months after the end of treatment. 12. Subjects voluntarily participate in this study, have good compliance, and cooperate with safety and survival follow up.

排除标准：

1. 受试者既往或同时患有其它恶性肿瘤（已治愈的皮肤基底细胞癌和宫颈原位癌除外）； 2. 已知受试者既往对大分子蛋白制剂，或已知对应用的药物成分过敏； 3. 受试者存在任何活动性自身免疫病或有自身免疫病病史（如以下，但不局限于：自身免疫性肝炎、间质性肺炎，葡萄膜炎，肠炎，肝炎，垂体炎，血管炎，肾炎，甲状腺功能亢进，甲状腺功能降低，既往曾接受过甲状腺手术者不能纳入；受试者患有白癜风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；受试者需要支气管扩张剂进行医学干预的哮喘则不能纳入）； 4. 受试者正在使用免疫抑制剂、或全身性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），并在入组前4周内仍在继续使用的； 5. 有未能良好控制的心脏临床症状或疾病，如： (1) NYHA2级以上心力衰竭 (2) 不稳定型心绞痛 (3) 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的患者； 6. 受试者有活动性感染或在筛选期间、首次给药前发生原因不明发热>38.5度（经研究者判断，受试者因肿瘤产生的发热可以入组）； 7. 既往和目前有肺纤维化史、间质性肺炎、尘肺、放射性肺炎、药物相关肺炎、肺功能严重受损等客观证据的患者； 8. 受试者先天或后天免疫功能缺陷，如HIV感染者； 9. 研究用药前不足4周内或可能于研究期间接种活疫苗； 10. 受试者已知有精神类药物滥用、酗酒或吸毒史； 11. 不能口服给药的患者； 12. 首次给药前2周内曾接受具有抗肿瘤适应症的中草药或中成药； 13. 研究者认为应排除在本研究之外，例如经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素，如，其他的严重疾病（含精神疾病）需要合并治疗，有严重的胃底食管静脉曲张，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到受试者的安全，或资料及样品的收集。

Exclusion criteria：

1.The subject has a prior or concurrent other malignancy (except for cured cutaneous basal cell carcinoma and cervical carcinoma in situ). 2. Known history of allergy to macromolecular protein preparations or to any component of the study drugs. 3. The subject has any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects who have undergone thyroid surgery cannot be enrolled). Subjects with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be enrolled. Subjects requiring bronchodilators for medical intervention for asthma cannot be enrolled. 4. The subject is receiving immunosuppressive agents or systemic corticosteroid therapy for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent), and this therapy is ongoing within 4 weeks prior to enrollment. 5. Presence of poorly controlled cardiac clinical symptoms or diseases, such as: (1) heart failure of NYHA class ≥2; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention. 6. The subject has an active infection or unexplained fever >38.5°C during the screening period or before the first dose (subjects with fever due to tumor may be enrolled at the investigator's discretion). 7. Past or current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired lung function. 8. The subject has congenital or acquired immunodeficiency, such as HIV infection. 9. Receipt of live vaccine within less than 4 weeks prior to study drug administration or potential receipt of live vaccine during the study period. 10. The subject has a known history of substance abuse, alcohol abuse, or drug addiction. 11. Patients unable to take oral medication. 12. Receipt of Chinese herbal medicine or traditional Chinese patent medicine with anti tumor indications within 2 weeks prior to the first dose. 13. The investigator judges that the subject should be excluded from this study, for example, the presence of other factors that may lead to premature termination of the study, such as other serious diseases (including psychiatric disorders) requiring concomitant treatment, severe gastric/esophageal varices, serious laboratory abnormalities, or family/social factors that may affect the subject's safety or the collection of data and samples.

研究实施时间：

Study execute time：

从 From 2026-01-01 00:00:00至 To 2028-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2026-05-17 00:00:00 至 To 2028-12-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

31

Group：

Trial group

Sample size：

干预措施：

针对选定的大肿块接受空间分割放疗（SFRT）；晶格区域放疗结束后次日至1周内联合替雷利珠单抗和抗血管生成靶向药物；抗血管生成靶向药物选自：仑伐替尼、瑞戈非尼、安罗替尼和索凡替尼（由研究者根据患者前期用药情况具体选定）。SFRT结束后4周进行首次疗效评价，后每6周进行1次影像学检查以评估疾病进展情况。受试者在结缔治疗后，将接受每2个月1次的生存随访。

干预措施代码：

Intervention：

Spatial fractionated radiotherapy (SFRT) for selected large tumors; concurrent Tislelizumab and anti-angiogenic targeted therapy within 1 to 7 days after completion of grid radiotherapy; anti-angiogenic targeted drugs include Lenvatinib, Regorafenib, Anlotinib, and Sunitinib (selected by investigators based on prior treatment history). First efficacy assessment at 4 weeks after SFRT completion, followed by imaging evaluation every 6 weeks to assess disease progression. After completion of treatment, participants will receive survival follow-up every 2 months.

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)：

北京大学国际医院 

单位级别：

三级医院 

Institution
hospital：

Peking University International Hospital

Level of the institution：

Tertiary

测量指标：

Outcomes：

指标中文名：

无进展生存时间（PFS）

指标类型：

主要指标

Outcome：

Progression-Free Survival

Type：

Primary indicator

测量时间点：

SFRT结束后4周进行首次疗效评价，后每6周进行1次影像学检查；随后每2个月1次的生存随访

测量方法：

Measure time point of outcome：

Four weeks after SFRT completion for first efficacy assessment, then every six weeks with imaging evaluation; followed by survival follow-up every two months

Measure method：

指标中文名：

接受SFRT大肿块的局部控制率

指标类型：

次要指标

Outcome：

Local Control Rate in Large Tumors Receiving SFRT

Type：

Secondary indicator

测量时间点：

SFRT结束后4周及每6周随访

测量方法：

Measure time point of outcome：

Four weeks and every six weeks post-SFRT

Measure method：

指标中文名：

远隔反应率

指标类型：

次要指标

Outcome：

Abscopal Response Rate

Type：

Secondary indicator

测量时间点：

SFRT结束后4周及每6周随访

测量方法：

Measure time point of outcome：

Four weeks and every six weeks post-SFRT

Measure method：

指标中文名：

疾病整体控制率

指标类型：

次要指标

Outcome：

Overall Disease Control Rate

Type：

Secondary indicator

测量时间点：

SFRT结束后4周及每6周随访

测量方法：

Measure time point of outcome：

Four weeks and every six weeks post-SFRT

Measure method：

指标中文名：

客观有效率（ORR）

指标类型：

次要指标

Outcome：

Objective Response Rate

Type：

Secondary indicator

测量时间点：

SFRT结束后4周及每6周随访

测量方法：

Measure time point of outcome：

Four weeks and every six weeks post-SFRT

Measure method：

指标中文名：

总生存时间（OS）

指标类型：

次要指标

Outcome：

Overall Survival

Type：

Secondary indicator

测量时间点：

生存随访期间

测量方法：

Measure time point of outcome：

During survival follow-up period

Measure method：

指标中文名：

AE（不良事件）发生情况及剂量调整

指标类型：

副作用指标

Outcome：

Incidence of Adverse Events and Dose Modifications

Type：

Adverse events

测量时间点：

研究治疗期间及随访

测量方法：

Measure time point of outcome：

During study treatment and follow-up

Measure method：

指标中文名：

血液标本免疫指标

指标类型：

附加指标

Outcome：

Immune Markers in Blood Specimens

Type：

Additional 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：

外周血

组织：

Sample Name：

Peripheral 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 NA 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:

不公开/Private

盲法：

无

Blinding：

None

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）：

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：

1. 数据采集内容： (1) 基线资料：包括人口统计学资料、疾病基线特征、基础器官功能和重要生物标志物、既往治疗史等。 (2) 空间分割放疗治疗数据：包括放疗计划数据、影像学基础、靶区勾画、放疗处方、放疗实施记录等。 (3) 系统药物治疗数据：包括用药记录、药物名称与剂量、用药时间、剂量调整记录等。 (4) 安全性与耐受性数据：不良事件发生情况。 (5) 疗效评价数据：影像学评估的时间点、评估标准，记录目标病灶、非目标病灶、新发病灶的变化情况以及总体疗效，计算ORR、DCR、PFS和OS等。 (6) 探索性生物标志物数据。 2. 数据管理流程 (1) 工具：使用临床电子数据采集系统（EDC）进行数据录入，将电子病历作为源数据验证的依据。 (2) 数据核查计划：在EDC中设置自动核查规则，定期进行源数据验证，核对EDC中数据与原始病历、检验报告、影像报告的一致性。 (3) 隐私与安全：所有研究数据去标识、保密。

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

1、Data Collection Content（1）Baseline data: Including demographic data, baseline disease characteristics, baseline organ function and important biomarkers, prior treatment history, etc.（2）Spatially fractionated radiotherapy (SFRT) treatment data: Including radiotherapy planning data, imaging basis, target delineation, radiotherapy prescription, radiotherapy delivery records, etc.（3）Systemic drug therapy data: Including medication records, drug names and doses, timing of administration, dose adjustment records, etc.（4）Safety and tolerability data: Occurrence of adverse events.（5）Efficacy evaluation data: Time points of imaging assessments, evaluation criteria, records of changes in target lesions, non target lesions, and new lesions, as well as overall efficacy; calculation of ORR, DCR, PFS, and OS, etc.（6）Exploratory biomarker data.2、Data Management Process（1）Tools: Use of a clinical electronic data capture (EDC) system for data entry, with electronic medical records serving as the source data for verification.（2）Data verification plan: Establish automatic verification rules within the EDC, conduct regular source data verification, and check the consistency between EDC data and original medical records, laboratory reports, and imaging reports.（3）Privacy and security: All study data will be de identified and kept confidential.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2026-05-17 19:57:50
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