ChiCTR2600126870 版本V1.0 版本创建时间2026/06/17 17:12:16 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：

 ChiCTR2600126870 

最近更新日期：

Date of Last Refreshed on：

 2026-06-17 17:11:56 

注册时间：

Date of Registration：

 2026-06-17 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

肝癌移植后复发靶向治疗失败后CapeOX+BEV治疗的有效性和安全性评价

Public title：

The efficacy and safety of CapeOX plus bevacizumab in the treatment of recurrent hepatocellular carcinoma after liver transplantation following failure of targeted therapy

注册题目简写：

English Acronym：

研究课题的正式科学名称：

肝癌移植后复发靶向治疗失败后CapeOX+BEV治疗的有效性和安全性评价

Scientific title：

The efficacy and safety of CapeOX plus bevacizumab in the treatment of recurrent hepatocellular carcinoma after liver transplantation following failure of targeted therapy

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：

杨明 

研究负责人：

杨明 

Applicant：

Ming Yang 

Study leader：

Ming Yang 

申请注册联系人电话：

Applicant telephone：

 +86 158 1009 2973

研究负责人电话：

Study leader's
telephone：

+86 158 1009 2973

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：

 ymicecream@163.com

研究负责人电子邮件：

Study leader's E-mail：

 ymicecream@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：

北京市昌平区立汤路168号

研究负责人通讯地址：

北京市昌平区立汤路168号

Applicant address：

168 Litang Road, Changping District, Beijing

Study leader's address：

168 Litang Road, Changping District, Beijing

申请注册联系人邮政编码：

Applicant postcode：

 100044

研究负责人邮政编码：

Study leader's postcode：

 100044

申请人所在单位：

北京清华长庚医院

Applicant's institution：

Beijing Tsinghua Changgung Hospital

研究负责人所在单位：

北京清华长庚医院

Affiliation of the Leader：

Beijing Tsinghua Changgung Hospital

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：

 25537-0-02

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：

北京清华长庚医院伦理委员会

Name of the ethic committee：

Ethics Committee of Beijing Tsinghua Changgung Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-07-24 00:00:00

伦理委员会联系人：

刘曼婷

Contact Name of the ethic committee：

Manting Liu

伦理委员会联系地址：

北京市昌平区立汤路168号

Contact Address of the ethic committee：

168 Litang Road, Changping District, Beijing

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 10 5611 8567

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：

北京清华长庚医院

Primary sponsor：

Beijing Tsinghua Changgung Hospital

研究实施负责（组长）单位地址：

北京市昌平区立汤路168号

Primary sponsor's address：

No.168, Litang Rd.,Dongxiaokou Town, Changping District

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

市(区县)：

北京市

Country：

China

Province：

Beijing

City：

Beijing

单位(医院)：

北京清华长庚医院

具体地址：

北京市昌平区立汤路168号

Institution
hospital：

Beijing Tsinghua Changgung Hospital

Address：

No.168, Litang Rd.,Dongxiaokou Town, Changping District

经费或物资来源：

北京市研究型病房卓越临床研究计划

Source(s) of funding：

Beijing Research Ward Excellence Clinical Research Program

研究疾病：

肝癌  

Target disease：

HCC

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：

单臂 

Study design：

Single arm 

研究目的：

评估HCC肝移植术后复发转移患者经TKI治疗失败后应用CapeOX+BEV方案治疗的疗效和安全性。  

Objectives of Study：

To evaluate the efficacy and safety of the combination of capecitabine plus oxaliplatin (CapeOX) and bevacizumab (BEV) in patients with hepatocellular carcinoma (HCC) who have failed to respond to tyrosine kinase inhibitor (TKI) therapy after liver transplantation.

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.年龄≥18岁，男女不限； 3.经病理学明确诊断为肝细胞癌； 4.既往行肝移植术，术后出现复发转移； 5.肝移植术后经过至少一线TKI治疗失败或不能耐受； 6.依据实体瘤疗效评价标准1.1版（RECIST v1.1）标准，至少有1个可测量的病灶； 7.ECOG PS：0或1； 8.肝功能Child-Pugh：≤7分； 9.预期生存时间≥12周； 10.主要器官功能符合下列要求（入组前7天内）： 1)血常规检查须符合以下标准： A.中性粒细胞≥1.5×10^9/L，不能通过使用粒细胞集落刺激因子达到要求； B.血小板≥75×10^9/L，不能通过输血来达到此要求； C.血红蛋白≥90g/L； 2)血生化检查须符合以下标准： A.血清白蛋白≥30g/L； B.总胆红素≤2×ULN（胆道梗阻允许胆道引流）； C.谷草转氨酶≤3×ULN（对于肝转移患者，可放宽至≤5×ULN）； D.谷丙转氨酶≤3×ULN（对于肝转移患者，可放宽至≤5×ULN）； E.肌酐清除率≥50 ml/min或血清肌酐≤1.5×ULN； 3)国际标准化比率（INR）≤2.0或凝血酶原时间（PT）超过正常对照的范围≤4秒； 4)尿蛋白＜2+（若尿蛋白≥2+者需进行24小时（h）尿蛋白定量，24h尿蛋白定量＜1.0g可以入组）； 11.患有活动性乙型肝炎病毒感染的患者在筛选阶段开始进行抗乙型肝炎病毒治疗且愿意在研究期间全程接受抗病毒治疗；丙型肝炎病毒核糖核酸阳性患者必须按当地标准治疗指南接受抗病毒治疗且肝功能在CTCAE 1级升高以内； 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天内采用可靠方法避孕；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。 13.对于伴侣为有生育能力的妇女的男性患者，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天内采用可靠方法避孕。在同一时间段内男性患者也必须同意不捐精子。

Inclusion criteria

1. The patients voluntarily join the study and sign the informed consent form; 2. Age >=18 years old, no gender restriction; 3. Hepatocellular carcinoma is confirmed by pathology; 4. Previous liver transplantation, recurrence and metastasis after operation; 5. Failure or intolerance of at least first-line TKI after liver transplantation; 6. According to the standard of RECIST v1.1, there should be at least one measurable lesion; 7. ECOG PS: 0 or 1; 8. Child-Pugh liver function: <=7; 9. Expected survival time is >=12 weeks; 10. The function of major organs meets the following requirements (within 7 days before enrollment): 1) The blood routine examination must meet the following standards: A.Neutrophils >=1.5×10^9/L, which cannot be achieved by using granulocyte colony stimulating factor; B.The platelet count is >=75×10^9/L, which cannot be achieved by blood transfusion; C.Hemoglobin >=90g/L; 2) Blood biochemistry examination must meet the following criteria: A. Serum albumin >=30g/L; B. The total bilirubin is less than or equal to 2 x ULN (biliary obstruction allows biliary drainage); C. Glutamic transaminase <=3×ULN (for patients with liver metastasis, it can be relaxed to <=5×ULN); D. Alanine aminotransferase <=3x ULN (for patients with liver metastases, it can be relaxed to <=5x ULN); E. Creatinine clearance rate is >=50 ml/min or serum creatinine is <=1.5×ULN; 3) International standardization ratio (INR) is less than or equal to 2.0 or prothrombin time (PT) is more than the normal control range of less than or equal to 4 seconds; 4) Urinary protein <2+ (if urinary protein is >=2+,24-hour urine protein quantification is required, and 24-hour urine protein quantification <1.0g can be included in the group); 11. Patients with active hepatitis B virus infection who begin antiviral therapy during the screening phase and are willing to receive antiviral treatment throughout the study; patients with hepatitis C virus RNA-positive who must receive antiviral treatment according to local standard treatment guidelines and have liver function elevated to CTCAE grade 1 or less; 12. Women of childbearing age: must agree to use reliable contraception from the time of signing the informed consent form until at least 120 days after the last dose of the study drug; and the serum HCG test must be negative within 7 days before starting the study treatment; and must not be breastfeeding. 13. Male patients with a partner who is a fertile woman must agree to use reliable contraception from the time of signing the informed consent form until at least 120 days after the last dose of the study drug. During the same period, male patients must also agree not to donate sperm.

排除标准：

1.已知病理类型为肝内胆管细胞癌、肉瘤样肝细胞癌、混合细胞癌及纤维板层细胞癌；5年内或同时患有除肝细胞癌之外的其它恶性肿瘤。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.肝内肿瘤负荷超过50%患者、Vp3型及Vp4型门脉癌栓患者、弥漫性骨转移患者； 3.准备进行或者既往接受过同种异基因骨髓移植的患者； 4.有肝性脑病病史的患者； 5.有临床症状的中度、重度腹水，即需要治疗性穿刺、引流者或Child-Pugh评分中的腹水评分>2（仅影像学显示少量腹水但不伴有临床症状者除外）；不受控制的胸腔积液、心包积液； 6.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者需复查，复查后若仍为阳性，需要进行胃镜检查，若胃镜提示出血风险的食管胃底静脉曲张则不能入组）； 7.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）； 8.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； 9.有未能良好控制的心脏临床症状或疾病，如：（1）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%；（2）不稳定型心绞痛；（3）研究治疗开始前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；（5）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）； 10.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； 11.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：在初始诊断时如果有不完全梗阻/梗阻综合征/肠梗阻体征/症状的患者接受了明确（外科）治疗以消退症状时，患者则可入组； 12.既往或目前存在中枢神经系统转移； 13.既往和目前有肺纤维化史、机化性肺炎（例如，闭塞性细支气管炎）、间质性肺炎、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等可能会干扰可疑的药物相关肺毒性的检测和处理的受试者，不允许辐射区曾有放射性肺炎； 14.在开始研究治疗之前28天内接受过减毒活疫苗治疗，或预期于治疗期间至末次给药后60天内需要接种此类疫苗； 15.活动性结核；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）；患者有活动性感染、入组前7天内有不明原因发热≥38.5℃、或基线期白细胞计数>15×10^9/L； 16.已知对研究药物或辅料过敏者； 17.研究者认为不适合参加该研究的其他因素。

Exclusion criteria：

1. Known pathological types include intrahepatic cholangiocarcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma, and fibroblastic cell carcinoma; having had other malignant tumors other than hepatocellular carcinoma within the past 5 years or at the same time. Cured localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, and breast carcinoma in situ, can be included in the group; 2. Patients with intrahepatic tumor load more than 50%, patients with Vp3 and Vp4 portal thrombosis, and patients with diffuse bone metastasis; 3. Patients who are preparing to undergo or have previously received allogeneic bone marrow transplantation; 4. Patients with a history of hepatic encephalopathy; 5. Moderate or severe ascites with clinical symptoms, that is, those who need therapeutic puncture and drainage or those with an ascites score>2 on Child-Pugh score (except those with minimal ascites on imaging but without clinical symptoms); uncontrolled pleural effusion, pericardial effusion; 6. Patients with a history of gastrointestinal bleeding or a clear tendency to bleed in the gastrointestinal tract within 6 months before the start of treatment, such as: esophageal or gastric varices with bleeding risk, locally active peptic ulcers, or persistent positive fecal occult blood, are not eligible for enrollment (if the fecal occult blood is positive at baseline, a retest is required; if it remains positive after retest, a gastroscopy is needed; if the gastroscopy indicates esophageal or gastric varices with bleeding risk, the patient is not eligible for enrollment); 7. Known hereditary or acquired bleeding (such as coagulation disorders) or thrombophilia, such as hemophilia; currently or recently (within 10 days before the start of the study treatment) using full doses of oral or injectable anticoagulants or thrombolytics for therapeutic purposes (low-dose aspirin or low molecular weight heparin is allowed for prophylaxis); 8. Patients who have had thrombosis or embolism events within 6 months before the start of treatment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.; 9. Clinical symptoms or diseases of the heart that are not well controlled, such as: (1) Heart failure according to the New York Heart Association (NYHA) standard II or higher, or echocardiography showing: LVEF (left ventricular ejection fraction) <50%; (2) Unstable angina; (3) Myocardial infarction within 1 year before the start of the study treatment; (4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) QTc> 450ms (men); QTc> 470ms (women) (QTc interval calculated using the Fridericia formula; if QTc is abnormal, measure three times consecutively with a 2-minute interval, and take the average); 10. Hypertensive patients who fail to achieve good control with antihypertensive medication (systolic blood pressure >=140mmHg or diastolic blood pressure >=90mmHg) (based on the average of BP readings obtained from >=2 measurements), and are allowed to achieve the above parameters through the use of antihypertensive therapy; those with a history of hypertensive crisis or hypertensive encephalopathy; 11. Patients who had intestinal obstruction and/or clinical signs or symptoms of gastrointestinal obstruction within 6 months before starting treatment, including incomplete obstruction related to pre-existing conditions or requiring routine parenteral hydration, parenteral nutrition, or tube feeding: Patients with incomplete obstruction/obstruction syndrome/intestinal obstruction signs/symptoms at initial diagnosis and who received definitive (surgical) treatment to resolve symptoms may be enrolled; 12. Past or present central nervous system metastasis; 13. Subjects with a history or current history of pulmonary fibrosis, organized pneumonia (e.g., obstructive bronchiolitis), interstitial pneumonia, pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or evidence of active pneumonia on chest computed tomography (CT) during the screening period, or severe impairment of lung function, which may interfere with the detection and management of suspected drug-related pulmonary toxicity, are not allowed to have had radiation pneumonitis in the radiation zone; 14. Received a live attenuated vaccine within 28 days before starting treatment, or is expected to need such a vaccine between treatment and 60 days after the last dose; 15. Active tuberculosis; severe infection within 4 weeks before starting the study treatment, including but not limited to hospitalization due to infection, bacteremia, or severe pneumonia complications; oral or intravenous administration of therapeutic antibiotics within 2 weeks before starting the study treatment (patients receiving prophylactic antibiotics, such as for urinary tract infections or exacerbations of chronic obstructive pulmonary disease, are eligible to participate in the study); patients have active infection, unexplained fever >=38.5°C within 7 days before enrollment, or a baseline white blood cell count>15×10^9/L; 16. Known to be allergic to the study drug or excipients; 17. Other factors that the investigator considers to disqualify participants from the study.

研究实施时间：

Study execute time：

从 From 2025-07-24 00:00:00至 To 2027-10-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-07-25 00:00:00 至 To 2027-10-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 29

Group：

Test group

Sample size：

干预措施：

奥沙利铂+卡培他滨+贝伐珠单抗

干预措施代码：

Intervention：

CapeOX plus bevacizumab

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 

市(区县)：

 北京市 

Country：

China

Province：

Beijing

City：

Beijing

单位(医院)：

 北京清华长庚医院 

单位级别：

 三级 

Institution
hospital：

Beijing Tsinghua Changgung Hospital

Level of the institution：

Tertiary

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：

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：

至缓解时间

指标类型：

次要指标

Outcome：

time to 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：

缓解持续时间

指标类型：

次要指标

Outcome：

duration of relief

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：

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：

血细胞减少

指标类型：

副作用指标

Outcome：

cytopenia

Type：

Adverse events

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

蛋白尿

指标类型：

副作用指标

Outcome：

albuminuria

Type：

Adverse events

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

高血压

指标类型：

副作用指标

Outcome：

hypertension

Type：

Adverse events

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 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）：

不涉及

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

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）：

研究结果发表之后的3 个月内，ResMan 网站

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

Within three months after the publication of the research findings, the ResMan website

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

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：

  2026-06-17 17:11:56