ChiCTR2100049735 版本V1.0 版本创建时间2022/03/08 17:36:58 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：

 ChiCTR2100049735 

最近更新日期：

Date of Last Refreshed on：

 2021-08-09 01:12:06 

注册时间：

Date of Registration：

 2021-08-09 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

抗PD-1抗体卡瑞利珠单抗、仑伐替尼或索拉非尼联合低分割放疗一线治疗寡转移肝细胞肝癌II期临床研究

Public title：

Anti-PD-1 antibody camrelizumab, lenvatinib or sorafenib combined with hypofractionated radiotherapy for the first-line treatment of oligometastatic hepatocellular carcinoma phase II clinical study

注册题目简写：

抗PD-1抗体卡瑞利珠单抗、仑伐替尼或索拉非尼联合低分割放疗一线治疗寡转移肝细胞肝癌II期临床研究

English Acronym：

Anti-PD-1 antibody camrelizumab, lenvatinib or sorafenib combined with hypofractionated radiotherapy for the first-line treatment of oligometastatic hepatocellular carcinoma phase II clinical study

研究课题的正式科学名称：

抗PD-1抗体卡瑞利珠单抗、仑伐替尼或索拉非尼联合低分割放疗一线治疗寡转移肝细胞肝癌II期临床研究

Scientific title：

Anti-PD-1 antibody camrelizumab, lenvatinib or sorafenib combined with hypofractionated radiotherapy for the first-line treatment of oligometastatic hepatocellular carcinoma phase II clinical study

研究课题代号(代码)：

Study subject ID：

 SDZL-SHR-1210-HCC-IIT-02

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：

岳金波 

研究负责人：

岳金波 

Applicant：

JINBO YUE 

Study leader：

JINBO YUE 

申请注册联系人电话：

Applicant telephone：

 15953176879

研究负责人电话：

Study leader's
telephone：

15953176879

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：

 yuejinbo@hotmail.com

研究负责人电子邮件：

Study leader's E-mail：

 yuejinbo@hotmail.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：

山东省济南市槐荫区济兖路440号

研究负责人通讯地址：

山东省济南市槐荫区济兖路440号

Applicant address：

No. 440 Jiyan Road, Huaiyin District, Jinan City, Shandong Province

Study leader's address：

No. 440 Jiyan Road, Huaiyin District, Jinan City, Shandong 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：

山东省肿瘤防治研究院

Applicant's institution：

Shandong Cancer Research Institute

研究负责人所在单位：

Affiliation of the Leader：

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：

 SDZLEC-2020-148-03

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：

山东省肿瘤防治研究院伦理委员会

Name of the ethic committee：

Ethics Committee of Shandong Cancer Research Institute

伦理委员会批准日期：

Date of approved by ethic committee：

 2021-07-28 00:00:00

伦理委员会联系人：

李朝伟

Contact Name of the ethic committee：

Li Chaowei

伦理委员会联系地址：

山东省济南市槐荫区济兖路440号

Contact Address of the ethic committee：

440 Jiyan Road, Huaiyin District, Jinan, Shandong

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

山东省肿瘤防治研究院

Primary sponsor：

Shandong Cancer Research Institute

研究实施负责（组长）单位地址：

山东省济南市槐荫区济兖路440号

Primary sponsor's address：

440 Jiyan Road, Huaiyin District, Jinan, Shandong

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

山东

市(区县)：

济南

Country：

China

Province：

Shandong

City：

Jinan

单位(医院)：

山东省肿瘤防治研究院

具体地址：

槐荫区济兖路440号

Institution
hospital：

Shandong Cancer Research Institute

Address：

440 Jiyan Road, Huaiyin District

经费或物资来源：

自筹经费

Source(s) of funding：

Self-financing

研究疾病：

肝癌  

Target disease：

hepatocellular carcinoma

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：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

本研究为小样本量探索性研究，主要研究目的是评估PD-1抗体卡瑞利珠单抗、仑伐替尼或索拉非尼联合低分割放疗一线治疗寡转移肝细胞癌耐受性。  

Objectives of Study：

This study is an exploratory study with a small sample size. The main purpose of the study is to evaluate the tolerance of the PD-1 antibody carrelizumab, lenvatinib or sorafenib combined with low-fraction radiotherapy in the first-line treatment of oligometastatic hepatocellular carcinoma.

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，男女均可； 2. 初诊的组织学或细胞学确诊为原发性HCC或按照中华人民共和国国家卫生健康委员会2019年版原发性肝癌诊疗规范，符合肝癌的临床诊断标准； 3. 1至5处远处转移灶的Ⅲb期寡转移肝细胞肝癌患者； 4. 肝功能Child-Pugh A、B期； 5. 至少有一处适合接受低分割放疗（包括原发病灶），具有可测量的，符合RECIST v1.1标准的可供评价病灶；可以有入组前稳定的脑转移但不在可测量病灶统计之内；骨转移病灶无软组织形成则可入组但不作为可测量病灶，如有软组织形成且满足可测量条件则被认为是可测量病灶； 6. ECOG评分：0～1； 7. 预期生存期大于3个月； 8. 重要器官的功能符合下列要求（不包括在14天内用任何血液成分及细胞生长因子）： 血常规检查标准需符合（14天内未输血及血制品）： 中性粒细胞绝对计数≥1.5×10^9/L； 血小板≥100×10^9/L； 血红蛋白≥9g/dL； 血清白蛋白≥3g/dL； 促甲状腺激素(TSH) ≤ULN（如异常应同时考察FT3、FT4水平，如FT3、FT4水平正常，可以入组）； 胆红素≤2倍ULN； ALT 和AST ≤1.5倍ULN； AKP ≤ 2.5倍ULN； 血清肌酐≤1.5倍ULN或肌酐清除率≥60mL/min。 9. 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。 10. 受试者自愿加入本研究，入组前签署书面知情同意书，依从性好，配合安全性和生存期随访。

Inclusion criteria

1. Aged 18-75 years, both male and female; 2. The initial diagnosis of HCC by histology or cytology is in accordance with the 2019 edition of the National Health Commission of the People's Republic of China for the diagnosis and treatment of primary liver cancer, and meets the clinical diagnostic criteria for liver cancer; 3. Patients with stage Ⅲb oligometastatic hepatocellular carcinoma with 1 to 5 distant metastases; 4. Liver function Child-Pugh A, B stage; 5. At least one area is suitable for receiving hypofractionated radiotherapy (including primary lesions), with measurable lesions that meet the RECIST v1.1 standard for evaluation; there may be stable brain metastases before enrollment but not included in the statistics of measurable lesions Within; bone metastases without soft tissue formation can be included in the group but not as measurable lesions, if there is soft tissue formation and meet the measurable conditions, it is considered as a measurable lesion; 6. ECOG score: 01; 7. The expected survival period is greater than 3 months; 8. The functions of vital organs meet the following requirements (not including the use of any blood components and cell growth factors within 14 days): Routine blood examination standards must meet (no blood transfusion and blood products within 14 days): The absolute count of neutrophils >= 1.5 x 10^9/L; Platelet >= 100 x 10^9/L; Hemoglobin >= 9g/dL; Serum albumin >= 3g/dL; Thyroid-stimulating hormone (TSH) <= ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin <= 2 times ULN; ALT and AST <= 1.5 times ULN; AKP <= 2.5 times ULN; Serum creatinine <= 1.5 times ULN or creatinine clearance >= 60 mL/min. 9. Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as intrauterine device, contraceptive or condom) during the study treatment and within 3 months after the end of the study treatment; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 7 days before enrollment in the study; and must be non-lactating; male patients of childbearing age who are not surgically sterilized must agree with their spouse during the study treatment period and the study Use a medically approved contraceptive method within 3 months after the end of the treatment period. 10. Subjects voluntarily joined the study, signed a written informed consent form before joining the group, had good compliance, and cooperated with safety and survival follow-up.

排除标准：

1. 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；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）； 2. 受试者正在使用免疫抑制剂、或全身、或可吸收的局部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2周内仍在继续使用的； 3. 对其他单克隆抗体发生过重度过敏反应； 4. 受试者有临床症状的中枢神经系统转移（如脑水肿、需要激素干预，或脑转移进展）。既往接受过脑或脑膜转移治疗，如临床稳定（MRI）已维持至少1个月，并且已经停止全身性激素治疗（剂量＞10mg/天泼尼松或其他等疗效激素）大于2周的患者可以纳入； 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（5）QTc＞450ms（男性）；QTc＞470ms (女性)； 6. 凝血功能异常（INR＞1.5或PT＞16s），出血倾向或正在接受溶栓或抗凝治疗； 7. 先前接受放疗、化疗、激素治疗、手术或分子靶向治疗，在治疗完成后(末次用药)，研究用药前不足4周的受试者（或5个药物半衰期，择其时间长者计算）；先前治疗引起的不良事件（脱发除外）未恢复至≤CTCAE 1度的患者； 8. 有临床症状的腹水、胸腔积液、心包积液，需要治疗性的穿刺或引流者，如胸腔积液、心包积液引流后至首次研究药物首次用药前至少观察2周稳定者，可以纳入研究； 9. 随机前2个月内存在明显的咳鲜血、或日咯血量达半茶勺（2.5ml）或以上者; 10. 已知存在的遗传性或获得性出血及血栓倾向（如血友病人，凝血机能障碍，血小板减少，脾功能亢进等）； 11. 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； 12. 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、肺功能严重受损等的客观证据的患者； 13. 受试者先天或后天免疫功能缺陷（如HIV感染者），或活动性肝炎（乙肝参考：HBV DNA检测值超过正常值上限；丙肝参考：HCV病毒滴度或RNA检测值超过正常值上限）； 14. 首次用药前4周内使用过其它药物临床试验研究药物或相似治疗药物者； 15. 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）； 16. 受试者在研究期间可能会接受其他全身抗肿瘤治疗； 17. 研究用药前不足4周内或可能于研究期间接种活疫苗； 18. 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 any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis , Nephritis, hyperthyroidism, reduced thyroid function; subjects suffering from vitiligo or asthma in childhood has completely resolved, and no intervention after adults can be included; subjects requiring bronchodilators for medical intervention can not be included in asthma); 2. Subjects are using immunosuppressive agents, or systemic or absorbable local hormone therapy to achieve immunosuppressive purposes (dose>10mg/day prednisone or other curative hormones), and within 2 weeks before enrollment Still in use; 3. Severe allergic reaction to other monoclonal antibodies; 4. The subject has central nervous system metastases with clinical symptoms (such as brain edema, need for hormonal intervention, or brain metastasis progression). Patients who have previously received brain or meningeal metastasis therapy, such as clinical stability (MRI) have been maintained for at least 1 month, and have stopped systemic hormone therapy (dose>10mg/day prednisone or other curative hormones) for more than 2 weeks can be included 5. Cardiac clinical symptoms or diseases that are not well controlled, such as: (1) Heart failure above NYHA level 2; (2) Unstable angina; (3) Myocardial infarction occurred within 1 year; (4) Supraventricular with clinical significance Or ventricular arrhythmia requires treatment or intervention; (5) QTc>450ms (male); QTc>470ms (female); 6. Abnormal coagulation function (INR>1.5 or PT>16s), bleeding tendency or receiving thrombolysis or anticoagulation therapy; 7. Subjects who have previously received radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy, after the completion of the treatment (last medication), and less than 4 weeks before the study medication (or 5 drug half-lives, whichever is longer)); patients whose adverse events (except hair loss) caused by previous treatment have not recovered to <= CTCAE 1 degree; 8. Patients with clinical symptoms of ascites, pleural effusion, and pericardial effusion that require therapeutic puncture or drainage, such as those who are stable after the drainage of pleural effusion and pericardial effusion until the first study drug is used for at least 2 weeks Included in the study; 9. Obvious hemoptysis in the 2 months before randomization, or the daily volume of hemoptysis reached half a teaspoon (2.5ml) or more; 10. Known hereditary or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.); 11. The subject has an active infection or a fever of unknown cause> 38.5 degrees during the screening period and before the first administration; 12. Past and current patients with objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lung function, etc.; 13. Subjects with congenital or acquired immune deficiencies (such as HIV infection), or active hepatitis (hepatitis B reference: HBV DNA test value exceeds the upper limit of normal value; hepatitis C reference: HCV virus titer or RNA test value exceeds the upper limit of normal value); 14. Those who have used other drugs in clinical trials or similar treatment drugs within 4 weeks before the first use of the drug; 15. The subject has previously or simultaneously suffered from other malignant tumors (except for cured skin basal cell carcinoma and cervical carcinoma in situ); 16. The subject may receive other systemic anti-tumor treatments during the study period; 17. Live vaccine may be vaccinated less than 4 weeks before study medication or may be administered during the study period; 18. According to the judgment of the investigator, the subject has other factors that may cause the study to be terminated midway, such as other serious diseases (including mental illness) requiring combined treatment, severe laboratory abnormalities, and family or Social and other factors will affect the safety of subjects or the collection of data and samples.

研究实施时间：

Study execute time：

从 From 2021-06-01 00:00:00至 To 2023-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2021-08-01 00:00:00 至 To 2022-10-31 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：

免疫联合靶向与放疗

干预措施代码：

Intervention：

Immune combined targeted therapy and radiotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 山东 

市(区县)：

 济南 

Country：

China

Province：

Shandong

City：

Jinan

单位(医院)：

 山东省肿瘤防治研究院 

单位级别：

 三级甲等 

Institution
hospital：

Shandong Cancer Research Institute

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

耐受性

指标类型：

主要指标

Outcome：

Tolerance

Type：

Primary 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：

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：

客观缓解率

指标类型：

次要指标

Outcome：

objective response 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：

6个月无进展生存期

指标类型：

次要指标

Outcome：

6 months progression-free survival

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：

尚未开始

Not yet 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)：

no

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：

Blinding：

是否共享原始数据：

IPD sharing

否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）：

临床试验公共平台管理

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

http://www.medresman.org.cn

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：

病例报告表CRF

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：

无/No

注册人：

Name of Registration：

  2021-08-09 01:12:06