中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2000034829
最近更新日期： Date of Last Refreshed on：	2020-07-22 00:14:12
注册时间： Date of Registration：	2020-07-21 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	卡瑞利珠单抗联合阿帕替尼对比化疗用于初治不可切除原发性肝癌的随机、对照、单中心临床研究
Public title：	Camrelizumab Plus Apatinib Versus Chemotherapy for Initial Primary Unresectable Hepatic Carcinoma: a Randomized, Controlled, Single-Center, Phase II Study
注册题目简写：
English Acronym：
研究课题的正式科学名称：	卡瑞利珠单抗联合阿帕替尼对比化疗用于初治不可切除原发性肝癌的随机、对照、单中心临床研究
Scientific title：	Camrelizumab Plus Apatinib Versus Chemotherapy for Initial Primary Unresectable Hepatic Carcinoma: a Randomized, Controlled, Single-Center, Phase II Study
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：	陈俊	研究负责人：	戴朝六/郑伟
Applicant：	Jun Chen	Study leader：	Chaoliu Dai, Wei Zheng
申请注册联系人电话： Applicant telephone：	+86 18940252977	研究负责人电话： Study leader's telephone：	+86 18940257707; +86 18940251697
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：	616chj@163.com	研究负责人电子邮件： Study leader's E-mail：	daicl@sj-hospital.org
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：	中国辽宁省沈阳市和平区三好街36号	研究负责人通讯地址：	中国辽宁省沈阳市和平区三好街36号
Applicant address：	36 Sanhao Street, Heping District, Shenyang, Liaoning, China	Study leader's address：	36 Sanhao Street, Heping District, Shenyang, Liaoning, 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：	中国医科大学附属盛京医院
Applicant's institution：	Shengjing Hospital Affiliated to China Medical University
研究负责人所在单位：	中国医科大学附属盛京医院
Affiliation of the Leader：	Shengjing Hospital Affiliated to China Medical University

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：	2020PS453K	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：	中国医科大学附属盛京医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Shengjing Hospital Affiliated to China Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2020-05-11 00:00:00
伦理委员会联系人：	王洪
Contact Name of the ethic committee：	Hong Wang
伦理委员会联系地址：	中国辽宁省沈阳市和平区三好街36号
Contact Address of the ethic committee：	36 Sanhao Street, Heping District, Shenyang, Liaoning, China
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：

中国医科大学附属盛京医院

Primary sponsor：

Shengjing Hospital Affiliated to China Medical University

研究实施负责（组长）单位地址：

中国辽宁省沈阳市和平区三好街36号

Primary sponsor's address：

36 Sanhao Street, Heping District, Shenyang, Liaoning, 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)：	辽宁	市(区县)：	沈阳
Country：	China	Province：	Liaoning	City：	Shenyang
单位(医院)：	中国医科大学附属盛京医院	具体地址：	和平区三好街36号
Institution hospital：	Shengjing Hospital Affiliated to China Medical University	Address：	36 Sanhao Street, Heping District

经费或物资来源：

自立项目

Source(s) of funding：

Independent project

研究疾病：

肝癌

Target disease：

Hepatic 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：

随机平行对照

Study design：

Parallel

研究目的：

观察和评价在初治不可切除IIb-IIIa期原发性肝癌患者中，卡瑞利珠单抗联合阿帕替尼对比氟尿嘧啶类联合奥沙利铂化疗作为转化治疗的有效性和安全性

Objectives of Study：

Evaluate the safety and efficacy of Camrelizumab Plus Apatinib Compared to Chemotherapy for the patients with initial unresectable primary hepatic 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：

Inclusion criteria

1. The patient must sign the informed consent and be willing and able to comply with the visit, treatment plan, laboratory examination and other requirements of the study schedule;
2. Age: 18-75 years old, including 18 years old and 75 years old (calculated from the date of signing informed consent), both male and female;
3. Patients with IIB IIIA stage hepatocellular carcinoma or intrahepatic cholangiocarcinoma;
4. The study only included patients who were newly diagnosed and could not be resected, which was evaluated by a team of gastroenterologists, oncologists, interventional radiologists and liver surgery; the definition of unresectable hepatobiliary carcinoma was that the liver was widely bilobar, with single huge tumor or multiple tumor invasion, or the tumor invaded the main portal vein, hepatic vein, inferior vena cava, main hepatic artery and liver Internal bile duct;
5. Patients without extrahepatic metastasis;
6. Patients with child Pugh grade A / better grade B of liver function;
7. Patients who have not received anti-tumor treatment for liver cancer in the past, including chemotherapy and local treatment;
8. The patients whose ECoG score (PS score) <= 1;
9. Patients whose function of important organs meets the following requirements (excluding the use of any blood components and cell growth factors during screening period);
(1) The results showed that the absolute count of neutrophils >= 1.5 * 10^9 / L; platelets >= 100 * 10^9 / L; hemoglobin >= 9 g / dl; serum albumin >= 2.8 g / dl;
(2) Thyroid stimulating hormone (TSH) <= 1 times ULN (if abnormal, T3 and T4 levels should be examined at the same time; if T3 and T4 levels are normal, they can be included in the group);
(3) Bilirubin <= 1.5 times ULN, ALT and AST <= 3 times ULN;
(4) Serum creatinine <=1.5 times ULN.
10. Female patients of non-surgical sterilization or childbearing age need to use a medically approved contraceptive method (such as intrauterine device, contraceptive or condom) during the study treatment period and within 3 months after the end of the study treatment period; the serum or urine HCG test of non-surgical sterilization women of childbearing age must be negative within 72 hours before the study enrollment; and they must be non lactating period; and For male, it is necessary to perform surgical sterilization or agree to use appropriate contraceptive methods during the trial period and within 3 months after the last administration of the trial drug.

排除标准：

1. 存在需治疗的并发症，如有临床症状的腹水或胸腔积液，即需要治疗性的穿刺或引流；或未切除的肿瘤存在活动出血；
2. 既往或者同时患有其他恶性肿瘤，除外经过充分治疗的非黑色素瘤皮肤癌、宫颈原位癌和甲状腺乳头状癌；
3. 活动性乙型或丙型肝炎（乙肝：HBsAg阳性且HBV-DNA≥10?copies/ml；丙肝：HCV抗体及HCV-RNA阳性，需要同时抗病毒治疗）；
4. 有活动性肺结核感染。在用药前1年内有活动性肺结核感染的患者，即使已经治疗，也要排除；超过1年以前有活动性肺结核感染病史的患者也要排除，除非证明以前接受过规范的抗结核治疗。
5. 患有活动性、已知或可疑的自身免疫性疾病（包括但不限于：葡萄膜炎，肠炎，肝炎，垂体炎，肾炎，血管炎，甲状腺功能亢进，甲状腺功能减退和需要支气管扩张剂治疗的哮喘等）。只需接受激素替代治疗的甲状腺功能减退症、无需进行全身治疗的皮肤疾病（如白癜风、银屑病或脱发）的受试者可以入选。
6. 既往有间质性肺病，或有（非感染性）肺炎且需要口服或静脉类固醇激素治疗。
7. 需要长期接受全身性激素（剂量相当于＞10mg强的松/天）或者其他任何形式的免疫抑制治疗。使用吸入性或外用皮质类固醇的受试者可以入选；
8. 未得到良好控制的心脏疾病，如：
（1）纽约心脏病协会（NYHA）2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、需要治疗或干预的室上性或室性心律失常。
9. 患有高血压，且经降压药物治疗无法获得良好控制（收缩压≥140 mmHg或者舒张压≥90 mmHg）；
10. 凝血功能异常（PT>16s、APTT>43s、TT>21s、Fbg<2g/L），具有出血倾向或正在接受溶栓或抗凝治疗；
11. 首次前3个月内出现过显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、出血性胃溃疡、基线期大便潜血++及以上，或患有脉管炎等；
12. 已知受试者既往对大分子蛋白制剂，或任何卡瑞利珠单抗组成成分过敏；
13. 需要全身性治疗的活动性感染。
14. 人类免疫缺陷病毒（HIV，HIV 1/2抗体）阳性。
15. 在卡瑞利珠单抗给药前30天内接种过或即将接种活疫苗。
16. 有精神类药物滥用、酗酒或吸毒史。
17. 经研究者判断可能影响受试者安全或试验依从性的其他因素。如需要合并治疗的严重疾病（包括精神疾病）、严重的实验室检查异常，或其他家庭或社会因素等。

Exclusion criteria：

1. Patients with complications that need to be treated, such as ascites or pleural effusion with clinical symptoms, need therapeutic puncture or drainage; or the unresected tumor has active bleeding;
2. Patients who have suffered from other malignant tumors before or at the same time are excluded from those who have received adequate treatment for non melanoma skin cancer, cervical carcinoma in situ and papillary thyroid carcinoma;
3. Patients with active hepatitis B or C (hepatitis B: HBsAg positive and HBV-DNA >= 10 copies / ml; hepatitis C: positive for HCV antibody and HCV-RNA, requiring antiviral treatment at the same time);
4. Patients with active tuberculosis infection. Patients with active tuberculosis infection within one year before medication should be excluded even if they have been treated; patients with active tuberculosis infection history more than one year should also be excluded, unless it is proved that they have received standard anti tuberculosis treatment before.
5. Patients with active, known or suspected autoimmune diseases (including but not limited to uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchodilator treatment). Subjects with hypothyroidism who received hormone replacement therapy only and skin diseases (such as vitiligo, psoriasis or alopecia) without systemic treatment could be enrolled;
6. Patients with previous interstitial lung disease or (non infectious) pneumonia need oral or intravenous steroid therapy.
7. Patients who need long-term systemic hormone therapy (dose equivalent to more than 10 mg prednisone / day) or any other form of immunosuppressive therapy. Subjects who used inhaled or topical corticosteroids could be enrolled;
8. Patients with poorly controlled heart disease, such as:
(1) NYHA grade 2 and above heart failure;
(2) Unstable angina pectoris;
(3) Myocardial infarction occurred within 1 year;
(4) Supraventricular or ventricular arrhythmias with clinical significance and need treatment or intervention.
9. Patients with hypertension who cannot be well controlled by antihypertensive drugs (SBP >= 140 mmHg or DBP >= 90 mmHg);
10. Patients with abnormal coagulation function (PT > 16S, APTT > 43S, TT > 21s, FBG < 2G / L) had bleeding tendency or were receiving thrombolytic or anticoagulant therapy;
11. In the first 3 months, there were significant bleeding symptoms or bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood + + or above, or vasculitis;
12. The subjects were known to have been allergic to macromolecular protein preparations or to any component of carrizumab;
13. Patients with active infection who need systemic treatment;
14. Patients with HIV, HIV 1 / 2 antibody positive;
15. Patients who have received or will be vaccinated with live vaccine within 30 days before the administration of carrizumab;
16. Patients with a history of psychotropic substance abuse, alcoholism or drug abuse;
17. Patients with other factors that may affect the safety or compliance of the test determined by the researcher. For example, serious diseases (including mental diseases), serious laboratory abnormalities, or other family or social factors that need to be treated together.

研究实施时间：

Study execute time：

从 From 2020-07-01 00:00:00至 To 2023-08-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2020-08-01 00:00:00 至 To 2021-08-31 00:00:00

干预措施：

Interventions：

组别：	卡瑞利珠单抗组	样本量：	30
Group：	Camrelizumab group	Sample size：	30
干预措施：	卡瑞利珠单抗联合阿帕替尼	干预措施代码：
Intervention：	Camrelizumab Plus Apatinib	Intervention code：

组别：	化疗组	样本量：	30
Group：	Chemotherapy group	Sample size：	30
干预措施：	氟尿嘧啶类联合奥沙利铂化疗	干预措施代码：
Intervention：	Fluorouracil combined with oxaliplatin chemotherapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

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)：	中国医科大学附属盛京医院	单位级别：	三级甲等
Institution hospital：	Shengjing Hospital Affiliated to China Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	R0切除率	指标类型：	主要指标
Outcome：	R0 resection 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：	显著的病理缓解率	指标类型：	次要指标
Outcome：	MPR	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	无病生存期	指标类型：	次要指标
Outcome：	DFS	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：	OS	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：	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）：

由研究者采用随机数字表法。

Randomization Procedure (please state who generates the random number sequence and by what method)：

Random number table method was used by the researchers.

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：	开放
Blinding：	open-label
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	联系研究者
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Contact the investigator
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
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：	2020-07-21 20:14:57