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：	ChiCTR2200067230
最近更新日期： Date of Last Refreshed on：	2023-05-08 11:21:23
注册时间： Date of Registration：	2022-12-30 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	PD-1单抗联合抗血管靶向药物二线治疗晚期结肠癌的前瞻性、观察性研究及生物标志物探索
Public title：	Prospective, observational study and biomarker exploration of PD-1 monoclonal antibody combined with angiogenesis targeting drugs in second-line treatment of advanced colon cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	PD-1单抗联合抗血管靶向药物二线治疗晚期结肠癌的前瞻性、观察性研究及生物标志物探索
Scientific title：	Prospective, observational study and biomarker exploration of PD-1 monoclonal antibody combined with angiogenesis targeting drugs in second-line treatment of advanced colon cancer
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：	纪洪辰	研究负责人：	张红梅
Applicant：	Ji Hongchen	Study leader：	Zhang Hongmei
申请注册联系人电话： Applicant telephone：	+86 15929894706	研究负责人电话： Study leader's telephone：	+86 13991293309
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：	jhca.xyt@163.com	研究负责人电子邮件： Study leader's E-mail：	zhm@fmmu.edu.cn
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：	陕西省西安市长乐西路127号	研究负责人通讯地址：	陕西省西安市长乐西路127号
Applicant address：	127 Changle Road, Xi'an, Shaanxi	Study leader's address：	127 Changle Road, Xi'an, Shaanxi
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：	空军军医大学第一附属医院
Applicant's institution：	First Affiliated Hospital of the Air Force Medical University
研究负责人所在单位：	空军军医大学第一附属医院
Affiliation of the Leader：	First Affiliated Hospital of the Air Force 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：	KY20222267-F-1	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：	空军军医大学第一附属医院医学伦理委员会审查批件
Name of the ethic committee：	Medical Ethics Committee of the First Affiliated Hospital of the Air Force Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2022-12-14 00:00:00
伦理委员会联系人：	贾艳艳
Contact Name of the ethic committee：	Jia Yanyan
伦理委员会联系地址：	陕西省西安市长乐西路127号
Contact Address of the ethic committee：	127 Changle Road, Xi'an, Shaanxi
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 29 84775518	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：

空军军医大学第一附属医院

Primary sponsor：

First Affiliated Hospital of the Air Force Medical University

研究实施负责（组长）单位地址：

陕西省西安市长乐西路127号

Primary sponsor's address：

127 Changle Road, Xi'an, Shaanxi

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	陕西	市(区县)：	西安
Country：	China	Province：	Shaanxi	City：	Xi'an
单位(医院)：	空军军医大学第一附属医院	具体地址：	长乐西路127号
Institution hospital：	First Affiliated Hospital of the Air Force Medical University	Address：	127 Changle Road

经费或物资来源：

空军军医大学临床研究课题

Source(s) of funding：

Clinical reseach foundation of Air Force Medical University

研究疾病：

结肠癌

Target disease：

Colon cancer

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：

其它

Study phase：

N/A

研究设计：

单臂

Study design：

Single arm

研究目的：

1.观察抗血管靶向药物联合PD-1单抗用于晚期结肠癌二线治疗的疗效与安全性。 2.构建一种可以有效预测PD-1单抗在结肠癌患者中疗效的预测模型。

Objectives of Study：

1. To observe the efficacy and safety of PD-1 monoclonal antibody combined with angiogenesis drugs in second-line treatment of advanced colon cancer. 2. To construct a prediction model that can effectively predict the efficacy of PD-1 monoclonal antibody in patients with colon cancer.

药物成份或治疗方案详述：

1. PD-1单抗（以下之一）：纳武利尤单抗注射液3mg/kg静滴1次/2周；替雷利珠单抗 200mg静滴 1次/3周；在研究过程中获批晚期结肠癌适应症、进入指南推荐或经项目负责人及研究者评估的其他适用的、可及的PD-1单抗。 2. 抗血管靶向药物（以下之一）：瑞戈非尼片80mg口服1次/日，d1-21，q28d；呋喹替尼胶囊 5mg 口服 1次/日，d1-21，q28d；在研究过程中获批晚期结肠癌适应症、进入指南推荐或经项目负责人及研究者评估的其他适用的、可及的抗血管靶向药物。

Description for medicine or protocol of treatment in detail：

1. PD-1 monoclonal antibody (one of the following) : Nivolumab intravenous injection 3 mg/kg once per 2weeks; Tirelizumab intravenous injection 200 mg once per 3weeks; Other applicable and accessible PD-1 monoantibodies approved for advanced colon cancer during the study, recommended by entry guidelines, or evaluated by program leaders and investigators. 2. Anti-vascular targeting drugs (one of the following) : Regorafenib, 80 mg orally 1 time/day, d1-21, q28d; Fruquintinib 5 mg oralyl 1 time/day, d1-21, q28d; Approved indications for advanced colon cancer during the study, recommended by entry guidelines or other applicable and accessible antivascular targeting agents evaluated by the program manager and investigator.

纳入标准：

Inclusion criteria

1. Join the group voluntarily and sign written informed consent;
2. Aged >= 18 years;
3. Recurrent or metastatic colon cancer confirmed by histology or cytology;
4. Progress after receiving 1-line system therapy;
5. According to the solid tumor efficacy evaluation criteria (RECIST Version 1.1), there was at least one radiographically measurable lesion. Lesions located in the previous radiation field can be regarded as measurable lesions if progression is confirmed;
6. The physical status (PS) score of ECOG was 0~1;
7. If the major organs are functioning normally, the following criteria are met:
(1) Hemoglobin >=90 g/L;
(2) Absolute neutrophil count (ANC) >=1.5x10^9/L;
(3) Platelet count >=100x10^9/L;
(4) Albumin >=28 g/L;
(5) Total bilirubin <=1.5x upper limit of normal value (ULN);
(6) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5xULN (ALT or AST <=5xULN for subjects with liver metastasis);
(7) Creatinine <=1.5xULN;
(8) International Normalized ratio (INR) or prothrombin time (PT) <=1.5xULN;
(9) Activated partial thromboplastin time (APTT) <=1.5xULN;
(10) Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. Subjects whose baseline TSH is outside the normal range can be enrolled if total T3 (or FT3) and FT4 are within the normal range;
(11) Myocardial enzyme profiles were within the normal range (simple laboratory abnormalities that were not clinically significant were also allowed to be included).

排除标准：

1. 首次研究药物给药前接受过放射治疗，符合以下情况之一： (1) 治疗前14天内曾有≥30%的骨髓接受过放射治疗； (2) 治疗前6周内接受过针对肺部病灶的放疗且剂量>30Gy（入组受试者必须从既往放疗的毒性中恢复至1级或以下，无需糖皮质激素治疗且无放射性肺炎病史）； (3) 姑息性放疗结束时间在首次研究药物给药前7天内； 2. 5年内患有其它恶性肿瘤，除非患者接受过可能的治愈性治疗并且5年内无该疾病存在的证据，但该时间要求（即5年内）不适用于成功接受了切除手术的皮肤基底细胞癌、皮肤鳞状细胞癌、浅表膀胱癌、宫颈原位癌或其他原位癌患者； 3. 存在其他抗血管靶向药物或PD-1单抗治疗禁忌症的患者； 4. 其它： (1) 入组前4周内接受过其它药物或医疗器械临床试验； (2) 无法遵循研究方案接受治疗或按期随访； (3) 其他任何研究者认为不能入组者。

Exclusion criteria：

1. Prior to the administration of the drug in the first study, one of the following conditions was met: (1) >=30% of bone marrow had received radiotherapy within 14 days prior to treatment; (2) Received radiotherapy for lung lesions within 6 weeks prior to treatment with a dose of >30Gy (enrolled subjects must recover from toxicity of previous radiotherapy to grade 1 or below, need no glucocorticoid therapy and have no history of radiation pneumonia); (3) The end time of palliative radiotherapy was within 7 days before the first study drug administration; 2. Other malignancies within 5 years, unless the patient has received potentially curable therapy and has no evidence of the disease within 5 years, but this time requirement (i.e. 5 years) does not apply to patients who have successfully undergone surgical excision for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, cervical carcinoma in situ or other carcinoma in situ; 3. Patients with contraindications to other anti-vascular targeting drugs or PD-1 monoabutances; 4. Other: (1) Received clinical trials of other drugs or medical devices within 4 weeks before enrollment; (2) Failure to follow the study protocol for treatment or follow-up; (3) Anyone who is considered not to be included by the researcher.

研究实施时间：

Study execute time：

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

征募观察对象时间：

Recruiting time：

从 From 2023-01-01 00:00:00 至 To 2024-06-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	40
Group：	Experimental group	Sample size：	40
干预措施：	PD-1单抗联合抗血管靶向药物	干预措施代码：
Intervention：	PD-1 monoclonal antibody combined with angiogenesis drugs	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	陕西	市(区县)：	西安
Country：	China	Province：	Shaanxi	City：	Xi'an
单位(医院)：	空军军医大学第一附属医院	单位级别：	三级甲等
Institution hospital：	First Affiliated Hospital of the Air Force Medical University	Level of the institution：	TertiaryA

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：	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：	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：	不良事件	指标类型：	次要指标
Outcome：	Adverse events	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：

标本中文名：	肿瘤组织	组织：	结肠癌
Sample Name：	tumor tissue	Tissue：	colon cancer
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	90	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）：

本研究为单臂研究，不适用随机方法

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

This study is a single-arm study, and random methods are not applicable

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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	在研究阶段不共享原始数据
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Raw data is not shared during the research phase
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：	1）电子病历报告表构建：本次研究采用电子化数据采集系统。数据管理员根据研究方案构建 eCRF。 2）数据录入：研究者对每位受试者在试验中的相关资料均应及时、真实地记录在研究病历中；研究者或其授权人员在规定的时间内使用电子录入系统（EDC）将相关资料及时、真实填写在电子病例报告表中。保证录入的内容与源数据一致。为保证患者的隐私权，患者姓名使用代码。 3）数据的修改和审核：数据录入人员或研究者核实数据后可对数据进行修改，修改的数据需在eCRF上填写修改理由。研究者对最终所有数据具有审核权限。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	1) Construction of electronic medical record report form: Electronic data acquisition system was adopted in this study. The data manager builds the eCRF according to the research scenario. 2) Data entry: The researcher shall timely and truthfully record the relevant data of each subject in the study medical record; The investigator or his/her authorized personnel shall use the electronic entry System (EDC) to fill in the electronic case report form in a timely and truthful manner within the specified time. Ensure that the input content is consistent with the source data. To ensure patient privacy, patient names are coded. 3) Data modification and review: Data entry personnel or researchers can modify the data after verifying the data, and the reason for modification shall be filled in the eCRF. Researchers have access to all final data.
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2022-12-30 15:23:07