ChiCTR2600119992 版本V1.0 版本创建时间2026/03/06 17:14:28 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：

ChiCTR2600119992 

最近更新日期：

Date of Last Refreshed on：

2026-03-06 17:14:12 

注册时间：

Date of Registration：

2026-03-06 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

大分割放疗联合免疫治疗原发性肝癌合并Vp3-Vp4 伴或不伴肝静脉癌栓患者疗效与安全性研究

Public title：

Study on the efficacy and safety of large-split radiotherapy combined immunotherapy for primary liver cancer combined with Vp3-Vp4 with or without hepatic vein cancer embolus

注册题目简写：

English Acronym：

研究课题的正式科学名称：

大分割放疗联合免疫治疗原发性肝癌合并Vp3-Vp4 伴或不伴肝静脉癌栓患者疗效与安全性研究

Scientific title：

Study on the efficacy and safety of large-split radiotherapy combined immunotherapy for primary liver cancer combined with Vp3-Vp4 with or without hepatic vein cancer embolus

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：

康小红 

研究负责人：

康小红 

Applicant：

Kang Xiaohong 

Study leader：

Kang Xiaohong 

申请注册联系人电话：

Applicant telephone：

+86 189 3752 1738

研究负责人电话：

Study leader's telephone：

+86 189 3752 1738

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：

kxhhgd@163.com

研究负责人电子邮件：

Study leader's E-mail：

kxhhgd@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：

河南省卫辉市健康路88号

研究负责人通讯地址：

河南省卫辉市健康路88号

Applicant address：

No. 88 Jiankang Road, Weihui City, Henan Province

Study leader's address：

No. 88 Jiankang Road, Weihui City, Henan 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：

河南医药大学第一附属医院

Applicant's institution：

The First Affiliated Hospital of Henan Medical University

研究负责人所在单位：

河南医药大学第一附属医院

Affiliation of the Leader：

The First Affiliated Hospital of Henan Medical University

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：

[2025]伦科会审字(37)号

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：

新乡医学院第一附属医院伦理委员会

Name of the ethic committee：

Ethics Committee of the First Affiliated Hospital of Xinxiang Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

2025-12-17 00:00:00

伦理委员会联系人：

常廷民

Contact Name of the ethic committee：

Tingmin Zhang

伦理委员会联系地址：

河南省卫辉市健康路88号

Contact Address of the ethic committee：

No. 88 Jiankang Road, Weihui City, Henan Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 373 440 2079

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：

河南医药大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Henan Medical University

研究实施负责（组长）单位地址：

河南省卫辉市健康路88号

Primary sponsor's address：

No. 88 Jiankang Road, Weihui City, Henan 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)：

河南省

市(区县)：

卫辉市

Country：

China

Province：

Henan Province

City：

Weihui City

单位(医院)：

河南医药大学第一附属医院

具体地址：

河南省卫辉市健康路88号

Institution
hospital：

The First Affiliated Hospital of Henan Medical University

Address：

No. 88 Jiankang Road, Weihui City, Henan Province

经费或物资来源：

无

Source(s) of funding：

None

Target disease：

HCC

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：

评估大分割放疗联合免疫治疗原发性肝癌合并Vp3-Vp4伴或不伴肝静脉癌栓患者的疗效和安全性。  

Objectives of Study：

Evaluate the efficacy and safety of hypofractionated radiotherapy combined with immunotherapy in patients with primary liver cancer complicated with Vp3-Vp4 with or without hepatic vein tumor thrombus.

药物成份或治疗方案详述：

筛查后，符合条件正式入组的患者，放疗开始时（±5天）进行信迪利单抗治疗。 放射治疗技术：采用IMRT/VMAT技术 靶区定义参考ICRU50号、62号、71号和83号报告的原则，具体如下： GTV：增强CT及MRI所显示门脉瘤栓/肝静脉瘤栓及其所相连的原发主体病灶，若部分子灶与上述靶区邻近，尽量包入GTV内； GTVboost：GTV均匀内缩1.0-1.5cm； PGTV:GTV前后左右外放0.5cm，上下外扩1.0cm；在瘤栓管壁方向上不外放，瘤栓沿血管方向放1.0cm；若有4DCT定位，给予参考。 正常组织勾画：包括十二指肠、结肠、小肠、胃、胰腺、肾、脊髓，脊髓PRV为脊髓外放0.5cm。 处方剂量： 95%GTVboost 30-35Gy/6-7Gy/5f；80-95%GTV 25Gy/5Gy/5f； 95%PGTV 20Gy/4Gy/5f； 免疫治疗：放疗开始时（±5天）开始使用，静脉输注（30-60分钟内）Q3W，直至疾病进展、死亡、毒性不能耐受、撤回知情同意、开始新的抗肿瘤治疗或方案规定的其他原因终止治疗。 放疗后1月进行首次影像学评估，以后治疗期间每9周进行一次影像学评估，直至发生疾病进展或死亡。针对非疾病进展/死亡原因结束治疗的受试者，还将在治疗结束后进行影像学评估直至发生进展/死亡事件。后续生存访视每3个月一次，直至死亡、撤回知情同意书或者研究结束。  

Description for medicine or protocol of treatment in detail：

After screening, eligible patients who are formally enrolled will receive sintilimab treatment at the start of radiotherapy (±5 days). Radiation therapy technology: IMRT/VMAT technology is adopted. Target volume definition refers to the principles in ICRU Reports No. 50, 62, 71, and 83, as follows: GTV: Portal vein tumor thrombus/hepatic vein tumor thrombus and their connected primary main lesions as shown by enhanced CT and MRI. If some sub-lesions are adjacent to the above target volumes, they should be included in the GTV as much as possible; GTVboost: GTV is uniformly contracted inward by 1.0-1.5 cm; PGTV: GTV is expanded outward by 0.5 cm anteriorly, posteriorly, leftward, and rightward, and by 1.0 cm superiorly and inferiorly; no expansion is made in the direction of the tumor thrombus vessel wall, and the tumor thrombus is expanded by 1.0 cm along the direction of the blood vessel; if 4DCT positioning is available, it shall be used for reference. Normal tissue delineation: Including duodenum, colon, small intestine, stomach, pancreas, kidney, and spinal cord. The spinal cord PRV is the spinal cord expanded outward by 0.5 cm. Prescribed dose: 95% GTVboost: 30-35 Gy/6-7 Gy/5 fractions; 80-95% GTV: 25 Gy/5 Gy/5 fractions; 95% PGTV: 20 Gy/4 Gy/5 fractions; Immunotherapy: It is administered at the start of radiotherapy (±5 days) via intravenous infusion (within 30-60 minutes) once every 3 weeks (Q3W) until treatment is terminated due to disease progression, death, intolerable toxicity, withdrawal of informed consent, initiation of new anti-tumor therapy, or other reasons specified in the protocol. The first imaging assessment is performed 1 month after radiotherapy, and subsequent imaging assessments are conducted every 9 weeks during treatment until disease progression or death occurs. For subjects who discontinue treatment for reasons other than disease progression/de 

纳入标准：

1. 按原发性肝癌诊疗指南2024版，经临床或病理组织学证实为肝细胞肝癌； 2. 年龄在18-80周岁； 3. 一般状态良好，ECOG 0-1分； 4. 剩余肝体积相对不足或肝功能相对较差，预估靶区包括门脉癌栓/肝静脉癌栓及其所相连的原发主体病灶后，预估Liver-GTV受到<5Gy照射的体积>150ml，＜350ml； 5. 既往可接受过介入、射频、手术、中草药等肝癌的治疗，但未接受过靶向治疗和抗PD-1、抗-PD-L1药物治疗； 6. BCLC C期，合并门静脉癌栓栓或者肝静脉癌栓，若为门脉癌栓需至少侵及门静脉左支或右支主干及以上，若为肝静脉癌栓需至少侵及肝左或肝中或肝右静脉主干及以上； 7. 预期生存期大于3个月； 8. Child-Pugh 分级:Child A-B； 9. 病毒指标:HBV DNA检测结果<20001U/mL,如果≥20001U/mL,需经抗病毒治疗后<20001U/mL:HCV抗体检测结果阳性的患者，需丙型肝炎病毒核糖核酸(HCVRNA)的聚合酶链式反应(PCR)检测结果为阴性； 10. 肝功能：ALT为正常上限2.5倍以内；AST可为正常上限的6倍以内，排除心脏梗塞所至AST升高； 11. 心电图检查未见明显异常，无明显心功能障碍； 12. 肾功能指标：CRE、BUN为正常值上限2.5倍以内； 13. 血常规指标：Hb≥80gL，ANC≥1.0*109/L，PLT≥40*109/L； 14. 凝血功能:无出血倾向； 15. 患者自愿参加本临床试验，并签署知情同意书；

Inclusion criteria

1. Confirmed as hepatocellular carcinoma by clinical or histopathological examination in accordance with the 2024 edition of the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer; 2. Aged 18-80 years; 3. In good general condition, with an ECOG score of 0-1; 4. Relatively insufficient remaining liver volume or relatively poor liver function. After estimating that the target area includes portal vein tumor thrombus/hepatic vein tumor thrombus and the connected primary main lesions, the estimated volume of Liver-GTV receiving <5Gy irradiation is >150ml and <350ml; 5. Having previously received treatments for liver cancer such as interventional therapy, radiofrequency ablation, surgery, and Chinese herbal medicine, but having not received targeted therapy, anti-PD-1, or anti-PD-L1 drug therapy; 6. BCLC stage C, complicated with portal vein tumor thrombus or hepatic vein tumor thrombus. If it is a portal vein tumor thrombus, it must invade at least the left branch, right branch trunk of the portal vein or above; if it is a hepatic vein tumor thrombus, it must invade at least the left hepatic vein, middle hepatic vein, right hepatic vein trunk or above; 7. Expected survival period of more than 3 months; 8. Child-Pugh classification: Child A-B; 9. Viral indicators: HBV DNA test result <20001U/mL; if ≥20001U/mL, it is required to be <20001U/mL after antiviral treatment; for patients with positive HCV antibody test results, the polymerase chain reaction (PCR) test result of hepatitis C virus ribonucleic acid (HCV RNA) must be negative; 10. Liver function: ALT within 2.5 times the upper limit of normal; AST within 6 times the upper limit of normal, excluding AST elevation caused by myocardial infarction; 11. No obvious abnormalities in electrocardiogram examination and no obvious cardiac dysfunction; 12. Renal function indicators: CRE and BUN within 2.5 times the upper limit of normal; 13. Routine blood indicators: Hb >=80g/L, ANC >=1.0*10?/L, PLT >=40*10?/L; 14. Coagulation function: no bleeding tendency; 15. Patients voluntarily participate in this clinical trial and sign the informed consent form;

排除标准：

1. 目前正在进行其他药物临床试验者； 2. 既往接受过腹部放疗，肝移植术后； 3. 有严重心脏、肾脏等重要器官慢性疾病者； 4. 怀疑或确有吸毒、药物滥用、酗酒者； 5. 可能对索拉非尼或特瑞普利治疗过敏； 6. 既往接受过抗 PD-1、抗-PD-L1药物的治疗或作用于另一种刺激性或共抑制性T细胞受体的药物(例如CTLA-4、OX-40或 CD137)的治疗患者； 7. 严重精神或神经系统疾患，影响知情同意和/或不良反应表述或观察； 8. 在过去6个月内曾被临床诊断为肝性脑病。使用利福昔明或乳果糖控制的肝性脑病受试者不允许参与研究； 9. 有明显症状的中重度腹水(达到Child-Pugh评分3分的腹水)； 10. 在研究开始前3年内有伴发的二次恶性肿瘤或其它肿瘤(浅表皮肤癌、局限性低度恶性肿瘤及原位癌除外)； 11. 入组前6个月内有过消化道出血病史，或者经ERCP/CT/DSA下诊断为食管胃底曲张静脉破裂出血高度危险； 12. 患有严重的未愈合伤口、溃疡或骨折； 13. 活动的中枢神经系统转移或癌性脑膜炎； 14. 活动性肺结核(TB)，正在接受抗结核治疗或者首次用药前1年内接受过抗结核治疗者； 15. 入组前4周内有胆瘘、胃肠道穿孔、腹腔内脓肿病史； 16. 入组前3个月内有不稳定性心绞痛、心肌梗塞、冠状动脉搭桥术、充血性心力衰竭、脑血管意外(包括短暂性脑缺血发作、肺动脉栓塞)； 17. 持续性心律失常(CTCAE标准2级及以上)，任何程度的房颤,QTC 间期延长(男性延长超过450毫秒，女性延长超过470毫秒)； 18. 难治性高血压(最佳药物治疗后血压仍然高于150/100 mmHg)； 19. 已知有人类免疫缺陷病毒(HIV)感染病史； 20. 孕期或者哺乳期妇女； 21. 在研究药物首次给药前30天内接种过活疫苗。活疫苗包括但不限于以下:麻疹、腮腺炎、水痘/带状疱疹(水痘)、黄热病、狂犬病、卡介苗(BCG)和伤寒疫苗。由于注射用季节性流感疫苗通常是灭活病毒疫苗，因此允许使用:但是，鼻内用流感疫苗(例如，X-40或FluMist) 为减毒活疫苗，因此不允许使用； 22. 在过去2年内患有需要全身性治疗的活动性自身免疫疾病(自身免疫性疾病如自身免疫性肝炎、间质性肺炎、葡萄膜炎、系统性红斑狼疮、类风湿性关节炎、炎性肠病、抗磷脂综合征相关的血管血栓形成，Wegener's肉芽肿病、干燥综合征、格林-巴利综合征、多发性硬化、血管炎、肾小球肾炎等、甲状腺功能亢进或减退、需要支气管扩张剂进行治疗的哮喘等即，免疫调节药物、皮质激素类药物或免疫抑制性药物)。替代治疗(例如 甲状腺素、胰岛素或因肾上腺或垂体功能不全而接受的生理性皮质类固醇替代治疗)不被视作全身治疗,允许使用。 23. 合并有不能接受任何造影增强成像检查(CT或MRI)的医学禁忌症； 24. 对研究干预和/或其任何辅料严重过敏者(≥3级)； 25. 不受控制的代谢紊乱或其它非恶性肿瘤器官或全身性疾病或癌症继发反应、并可导致较高医学风险和/或生存期评价不确定性； 26. 接受过同种异体组织/实体器官移植的受试者； 27. 可能会导致以下结果的其它急性或慢性疾病、精神疾病或实验室检测值异常的患者;增加研究参与或研究药物给药的相关风险，或者干扰研究结果的解读，而且根据研究者的判断将患者列为不符合参加本研究的资格。

Exclusion criteria：

1. Currently participating in other drug clinical trials; 2. Having received previous abdominal radiotherapy or having undergone liver transplantation; 3. Having severe chronic diseases of important organs such as the heart and kidneys; 4. Suspected or confirmed drug addicts, drug abusers, or alcoholics; 5. Likely to be allergic to sorafenib or toripalimab treatment; 6. Patients who have previously received anti-PD-1, anti-PD-L1 drugs, or drugs acting on another stimulatory or co-inhibitory T-cell receptor (such as CTLA-4, OX-40, or CD137); 7. Having severe mental or neurological disorders that affect informed consent and/or the expression or observation of adverse reactions; 8. Having been clinically diagnosed with hepatic encephalopathy in the past 6 months. Subjects with hepatic encephalopathy controlled by rifaximin or lactulose are not allowed to participate in the study; 9. Having moderate to severe ascites with obvious symptoms (ascites reaching a Child-Pugh score of 3 points); 10. Having had a secondary malignant tumor or other tumors (except superficial skin cancer, localized low-grade malignant tumors, and carcinoma in situ) within 3 years before the start of the study; 11. Having a history of gastrointestinal bleeding within 6 months before enrollment, or being at high risk of esophageal and gastric variceal bleeding as diagnosed by ERCP/CT/DSA; 12. Having severe unhealed wounds, ulcers, or fractures; 13. Having active central nervous system metastasis or carcinomatous meningitis; 14. Having active tuberculosis (TB), currently receiving anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year before the first dose; 15. Having a history of biliary fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks before enrollment; 16. Having unstable angina pectoris, myocardial infarction, coronary artery bypass grafting, congestive heart failure, or cerebrovascular accident (including transient ischemic attack, pulmonary embolism) within 3 months before enrollment; 17. Having persistent arrhythmia (CTCAE grade 2 or above), atrial fibrillation of any degree, or prolonged QTc interval (more than 450 milliseconds in men and more than 470 milliseconds in women); 18. Having refractory hypertension (blood pressure remains higher than 150/100 mmHg after optimal drug treatment); 19. Having a known history of human immunodeficiency virus (HIV) infection; 20. Pregnant or lactating women; 21. Having received a live vaccine within 30 days before the first administration of the study drug. Live vaccines include but are not limited to: measles, mumps, chickenpox/herpes zoster (varicella), yellow fever, rabies, bacillus Calmette-Guérin (BCG), and typhoid vaccines. Seasonal influenza vaccines for injection are usually inactivated virus vaccines and are therefore allowed; however, intranasal influenza vaccines (e.g., X-40 or FluMist) are live attenuated vaccines and are not allowed; 22. Having active autoimmune diseases requiring systemic treatment within the past 2 years (autoimmune diseases such as autoimmune hepatitis, interstitial pneumonia, uveitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sj?gren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis, hyperthyroidism or hypothyroidism, asthma requiring treatment with bronchodilators, etc., i.e., immunomodulatory drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment and is allowed; 23. Having medical contraindications that prevent any contrast-enhanced imaging examinations (CT or MRI); 24. Having severe allergies (>= grade 3) to the study intervention and/or any of its excipients; 25. Having uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary reactions to cancer, which may lead to higher medical risks and/or uncertainty in survival evaluation; 26. Subjects who have received allogeneic tissue/solid organ transplantation; 27. Patients with other acute or chronic diseases, mental illnesses, or abnormal laboratory test values that may result in: increasing the risks associated with study participation or administration of the study drug, or interfering with the interpretation of study results, and who, in the investigator's judgment, are ineligible to participate in this study.

研究实施时间：

Study execute time：

从 From 2026-03-15 00:00:00至 To 2028-03-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2026-03-15 00:00:00 至 To 2027-03-01 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

30

Group：

Experimental group

Sample size：

干预措施：

大分割放疗联合免疫

干预措施代码：

Intervention：

hypofractionated radiotherapy combined with immunotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 河南省 

市(区县)：

  

Country：

China 

Province：

Henan  

City：

 

单位(医院)：

河南医药大学第一附属医院 

单位级别：

三甲 

Institution
hospital：

The First Affiliated Hospital of Henan Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

总生存期

指标类型：

主要指标

Outcome：

Overall Survival, OS

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：

客观缓解率

指标类型：

次要指标

Outcome：

objective response rate, ORR

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性

指标类型：

次要指标

Outcome：

safety

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：

无

组织：

Sample Name：

None

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 80 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）：

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：

病例记录表

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：

暂未确定/Not yet

注册人：

Name of Registration：

  2026-03-06 17:14:12