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：	ChiCTR2300068003
最近更新日期： Date of Last Refreshed on：	2023-05-11 11:55:22
注册时间： Date of Registration：	2023-02-02 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	瑞戈非尼联合PD-1/PD-L1单抗及肝脏局部c-TACE治疗伴有肝脏转移的MSS型晚期结直肠癌的临床研究
Public title：	Clinical study of regorafenib combined with PD-1/PD-L1 monoclonal antibody and local c-TACE in the treatment of MSS advanced colorectal cancer with liver metastasis
注册题目简写：
English Acronym：
研究课题的正式科学名称：	瑞戈非尼联合PD-1/PD-L1单抗及肝脏局部c-TACE治疗伴有肝脏转移的MSS型晚期结直肠癌的临床研究
Scientific title：	Clinical study of regorafenib combined with PD-1/PD-L1 monoclonal antibody and local c-TACE in the treatment of MSS advanced colorectal cancer with liver metastasis
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：	罗会芹	研究负责人：	何义富
Applicant：	Luo Huiqin	Study leader：	He Yifu
申请注册联系人电话： Applicant telephone：	+86 189 5519 9630	研究负责人电话： Study leader's telephone：	+86 189 6378 9042
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：	lhqluo@163.com	研究负责人电子邮件： Study leader's E-mail：	834638033@qq.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：	安徽省合肥市蜀山区环湖东路107号	研究负责人通讯地址：	安徽省合肥市蜀山区环湖东路107号
Applicant address：	107 Huanhu East Road, Shushan District, Hefei, Anhui	Study leader's address：	107 Huanhu East Road, Shushan District, Hefei, Anhui
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：	中国科学技术大学附属第一医院
Applicant's institution：	The First Affiliated Hospital of University of Science and Technology of China
研究负责人所在单位：	中国科学技术大学附属第一医院
Affiliation of the Leader：	The First Affiliated Hospital of University of Science and Technology of China

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：	伦审2023第13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：	安徽省肿瘤医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Anhui Cancer Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2023-01-16 00:00:00
伦理委员会联系人：	钱立庭
Contact Name of the ethic committee：	Liting Qian
伦理委员会联系地址：	安徽省合肥市蜀山区环湖东路107号
Contact Address of the ethic committee：	107 Huanhu East Road, Shushan District, Hefei, Anhui
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 551 65327725	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：

中国科学技术大学附属第一医院

Primary sponsor：

The First Affiliated Hospital of University of Science and Technology of China

研究实施负责（组长）单位地址：

安徽省合肥市蜀山区环湖东路107号

Primary sponsor's address：

107 Huanhu East Road, Shushan District, Hefei, Anhui

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	安徽省	市(区县)：	合肥市
Country：	China	Province：	Anhui	City：	Hefei
单位(医院)：	中国科学技术大学附属第一医院	具体地址：	安徽省合肥市蜀山区环湖东路107号
Institution hospital：	The First Affiliated Hospital of University of Science and Technology of China	Address：	107 Huanhu East Road, Shushan District, Hefei, Anhui

经费或物资来源：

自筹

Source(s) of funding：

Self-funded

研究疾病：

肝脏转移的MSS型晚期结直肠癌

Target disease：

MSS type advanced colorectal cancer with liver metastasis

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：

主要研究目的：评价PD-1/PD-L1单抗联合瑞戈非尼和介入治疗肝脏转移的晚期结直肠癌的有效性次要研究目的：评价PD-1/PD-L1单抗联合瑞戈非尼和介入治疗晚期结直肠癌的安全性

Objectives of Study：

Main Research Objectives: To assess the effectiveness of PD-1/PD-L1 monoclonal antibody in combination with regorafenib and interventional treatment for advanced colorectal cancer with liver metastases. Secondary Research Objectives: To assess the safety of PD-1/PD-L1 monoclonal antibody in combination with regorafenib and interventional treatment for advanced colorectal cancer.

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

Inclusion Criteria:
1. Patients voluntarily participate in the research of this topic, have good compliance, can cooperate with the requirements of the experiment to complete observation and follow-up, and sign informed consent;
2. Age >= 18 years old, male or female;
3. Genetic testing is clearly MSS or pMMR type;
4. Patients with colorectal cancer diagnosed by histopathological examination;
5. Imaging diagnosis of liver metastasis, which can be accompanied by metastasis in other parts;
6. After evaluation, about 80% of the volume of metastases is in the liver, but 60% of the affected liver is normal tissue; or those who are deemed unsuitable for surgery after multidisciplinary discussion, or the patient refuses surgical treatment;
7. Failure of treatment with at least 2 previous regimens;
8. Estimated survival time >= 3 months;
9. Have at least 1 measurable lesion according to mRECIST/RECIST1.1 criteria;
10. For female subjects: should be surgically sterilized, postmenopausal patients, or agree to use a medically recognized method of contraception (e.g., IUD, pill, or condom) during study treatment and within 6 months of the end of study treatment period; A blood pregnancy test must be negative within 7 days prior to study administration and must be non-lactating. For male subjects: should be surgically sterilized or agree to use a medically recognized contraceptive method during study treatment and within 6 months of the end of study treatment period;
11. Able to understand the test requirements, willing and able to follow the test and follow-up procedures.
12. Sufficient organ function, subjects need to meet the following laboratory indicators:
(1) Absolute value (ANC) of neutrophils >= 1.5x10^9/L;
(2) Platelet >= 90×10^9/L;
(3) Hemoglobin> 9g/dL;
(4) Total bilirubin <=1.5× upper limit of normal value (ULN); or total bilirubin > ULN but direct bilirubin <= ULN
(5) ALT, AST and ALP <=5 × ULN; Serum creatinine <=1.5×ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) >= 60 ml/min;
(6) Good coagulation function, defined as the international normalized ratio (INR) or prothrombin time (PT) <= 1.5 times ULN;
(7) Thyroid function is normal, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, participants may also be enrolled if total T3 (or FT3) and FT4 are within the normal range;
Myocardial enzyme profiles within the normal range (if the investigator comprehensively judges that simple laboratory abnormalities are not clinically significant, enrollment is also allowed).

排除标准：

具有以下任何一项的患者不能入组本研究：
1.诊断为免疫缺陷或研究首次给药前14天内正在接受全身性糖皮质激素治疗或任何其他形式的免疫抑制疗法，允许使用生理剂量的糖皮质激素（≤10mg/天的泼尼松或等效药物）；
2.存在任何重度和/或未能控制的疾病的受试者。包括：
(1)血压控制不理想（收缩压≥150mmHg或舒张压≥100mmHg）；
(2)患有≥2级心肌缺血或心肌梗塞、心律失常（QTc≥470ms）及≥2级充血性心功能衰竭（纽约心脏病协会[NYHA]分级）；
(3)活动性或未能控制的严重感染(≥CTCAE 2级感染)；
(4)肝硬化、活动性肝炎*；*活动性肝炎（乙肝参考：HBsAg阳性，且HBV DNA检测值超过正常值上限；丙肝参考：HCV抗体阳性，且HCV病毒滴度检测值超过正常值上限）；注：符合入组条件的，乙肝表面抗原阳性或核心抗体阳性的受试者、丙型肝炎患者，需持续抗病毒治疗，以防止病毒激活。
(5)活动性梅毒者；
(6)肾功能衰竭需要血液透析或腹膜透析者；
(7)有免疫缺陷病史，包括HIV阳性或患有其它获得性、先天性免疫缺陷疾病，或有器官移植史者；
3.首次给药之前（第1周期，第1天）30天内接种过活疫苗；
4.妊娠、哺乳期、有生育能力未采取避孕措施的女性患者；
5.有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况研究者认为存在其他潜在风险不适合参加本研究；
6.已知对本研究药物等活性成分或辅料过敏者。

Exclusion criteria：

Patients with any of the following were not enrolled in this study: 1. Diagnosed immunodeficiency or being receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 14 days prior to the first administration of the study, allowing the use of physiologic doses of glucocorticoids (<= 10 mg/day of prednisone or equivalent); 2. Subjects with any severe and/or uncontrolled disease. Include: (1) Unsatisfactory blood pressure control (systolic blood pressure >= 150mmHg or diastolic blood pressure >=100mmHg); (2) Patients with grade >=2 myocardial ischemia or myocardial infarction, arrhythmia (QTc >=470ms) and grade >=2 congestive heart failure (New York Heart Association [NYHA] grade); (3) Active or uncontrolled severe infection (>= CTCAE grade 2 infection); (4) Cirrhosis, active hepatitis*; *Active hepatitis (hepatitis B reference: HBsAg positive and HBV DNA test above the upper limit of normal; Hepatitis C reference: positive HCV antibody and HCV virus titer above the upper limit of normal); Note: Subjects who meet the enrollment conditions, positive hepatitis B surface antigen or core antibody, and patients with hepatitis C need continuous antiviral therapy to prevent virus activation. (5) Those with active syphilis; (6) Renal failure requiring hemodialysis or peritoneal dialysis; (7) Have a history of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 3. Have received a live vaccine within 30 days before the first dose (cycle 1, day 1); 4. Female patients who are pregnant, lactating, and have childbearing potential and do not take contraception; 5. Medical history or disease evidence, abnormal treatment or laboratory test values that may interfere with the test results, prevent the subject from participating in the research throughout the study, or other situations that the investigator believes are not suitable for enrollment, and the investigator believes that there are other potential risks and is not suitable for participating in this study; Those who are known to be allergic to active ingredients such as drugs or excipients in this study.

研究实施时间：

Study execute time：

从 From 2023-02-01 00:00:00至 To 2025-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-02-02 00:00:00 至 To 2024-01-31 00:00:00

干预措施：

Interventions：

组别：	1	样本量：	35
Group：	one	Sample size：	35
干预措施：	介入方案：瑞戈非尼及PD-1/PD-L1治疗前1周内行肝脏c-TACE术，术中给药：雷替曲塞4mg。	干预措施代码：
Intervention：	Interventional protocol: regorafenib and PD-1/PD-L1 treatment within 1 week before liver c-TACE, intraoperative administration: raltitrexed 4mg.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	安徽省	市(区县)：	合肥市
Country：	China	Province：	Anhui	City：	Hefei
单位(医院)：	中国科学技术大学附属第一医院	单位级别：	三级甲等
Institution hospital：	The First Affiliated Hospital of University of Science and Technology of China	Level of the institution：	Tertiary A

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, ORR	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：	疾病控制率	指标类型：	次要指标
Outcome：	Disease Control Rate, DCR	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 Response, DOR	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, OS	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：

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		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）：

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）：	病例记录表
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	CRF
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：	2023-02-02 17:11:04