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：	ChiCTR2500099888
最近更新日期： Date of Last Refreshed on：	2025-03-31 16:31:19
注册时间： Date of Registration：	2025-03-31 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	新辅助免疫联合化疗治疗pMMR/MSS型局部进展期结肠癌的机制及临床研究
Public title：	Mechanism and clinical study of neoadjuvant immunotherapy combined with chemotherapy in the treatment of pMMR/MSS type locally advanced colon cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	新辅助免疫联合化疗治疗pMMR/MSS型局部进展期结肠癌的机制及临床研究
Scientific title：	Mechanism and clinical study of neoadjuvant immunotherapy combined with chemotherapy in the treatment of pMMR/MSS type locally 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：	伍龙	研究负责人：	甄运寰
Applicant：	Wu Long	Study leader：	Zhen Yunhuan
申请注册联系人电话： Applicant telephone：	+86 185 8587 0523	研究负责人电话： Study leader's telephone：	+86 181 1199 7880
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：	javenwu2008@sina.com	研究负责人电子邮件： Study leader's E-mail：	1207108565@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：	贵州省贵阳市云岩区贵医街28号	研究负责人通讯地址：	贵州省贵阳市云岩区贵医街28号
Applicant address：	NO.28 Guiyi Street，Guiyang City, Guizhou Province	Study leader's address：	NO.28 Guiyi Street，Guiyang City, Guizhou 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：	贵州医科大学附属医院
Applicant's institution：	The Affiliated Hospital of Guizhou Medical University
研究负责人所在单位：	贵州医科大学附属医院
Affiliation of the Leader：	The Affiliated Hospital of Guizhou 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：	2025伦审第(054)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：	贵州医科大学附属医院医学科学伦理委员会
Name of the ethic committee：	The Ethics Committee of the Affiliated Hospital of Guizhou Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2025-02-19 00:00:00
伦理委员会联系人：	李海洋
Contact Name of the ethic committee：	Li Haiyang
伦理委员会联系地址：	贵州省贵阳市云岩区贵医街28号
Contact Address of the ethic committee：	NO.28 Guiyi Street,Guiyang City, Guizhou Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 851 8675 2685	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：

贵州医科大学附属医院

Primary sponsor：

The Affiliated Hospital of Guizhou Medical University

研究实施负责（组长）单位地址：

贵州省贵阳市云岩区贵医街28号

Primary sponsor's address：

NO.28 Guiyi Street，Guiyang City, Guizhou Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	贵州省	市(区县)：	贵阳市
Country：	China	Province：	Guizhou Province	City：	Guiyang City
单位(医院)：	贵州医科大学附属医院	具体地址：	贵州省贵阳市云岩区贵医街28号
Institution hospital：	The Affiliated Hospital of Guizhou Medical University	Address：	NO.28 Guiyi Street，Guiyang City, Guizhou Province

经费或物资来源：

贵州省卫生健康高质量发展医学科研联合基金项目

Source(s) of funding：

Guizhou Province Health and Health High-Quality Development Medical Research Joint Fund Project

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：

本研究拟对pMMR/MSS型结肠癌患者行抗PD-1新辅助免疫治疗+新辅助化疗，化疗方案为mFOLFOX6或FOLFORI，观察新辅助免疫治疗后及术后并发症及近远期疗效，论证结肠癌新辅助免疫治疗的安全性、可行性和有效性；观察奥沙利铂或伊立替康对免疫治疗的不同影响；并通过多色免疫荧光技术，对比观察抗PD-1新辅助免疫治疗患者治疗前手术后TIME（包括肿瘤免疫细胞浸润、TLS等）变化，筛选结肠癌患者中抗PD-1新辅助免疫治疗疗效优势患者的生物标记物，以精准甄别出新辅助免疫治疗获益的特殊类型结肠癌，提高新辅助免疫治疗响应率；基于NGS超深度测序平台建立ctDNA动态检测，探讨抗PD-1新辅助免疫治疗前后及手术后ctDNA动态变化对患者预后的预示作用。从而，为结肠癌患者的治疗提供新的策略，使更多的结肠癌患者从新辅助免疫治疗中获益。

Objectives of Study：

In this study, patients with pMMR/MSS colon cancer were treated with anti-PD-1 neoadjuvant immunotherapy + neoadjuvant chemotherapy. The chemotherapy regimen was mFOLFOX6 or FOLFORI. The postoperative complications and short-term and long-term effects of neoadjuvant immunotherapy were observed to demonstrate colon cancer. Safety, feasibility and efficacy of neoadjuvant immunotherapy; observe the different effects of oxaliplatin or irinotecan on immunotherapy; and compare and observe the treatment of patients with anti-PD-1 neoadjuvant immunotherapy by multicolor immunofluorescence technology Changes in TIME (including tumor immune cell infiltration, TLS, etc.) before and after surgery, and screen the biomarkers of patients with superior anti-PD-1 neoadjuvant immunotherapy efficacy in colon cancer patients to accurately identify special types of neoadjuvant immunotherapy benefit Colon cancer, improve the response rate of neoadjuvant immunotherapy; establish ctDNA dynamic detection based on NGS ultra-deep sequencing platform, and explore the predictive role of ctDNA dynamic changes before and after anti-PD-1 neoadjuvant immunotherapy and after surgery on patient prognosis. Thus, it provides a new strategy for the treatment of colon cancer patients, so that more colon cancer patients can benefit from neoadjuvant immunotherapy.

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. Informed consent must be obtained from the subject voluntarily signed and dated in accordance with regulations and institutional guidelines prior to the implementation of any procedures related to the study protocol other than routine care content.
2. Age 18-75 years old.
3. There is definite histological evidence to confirm colorectal adenocarcinoma, and there are sufficient biopsy specimens for detection; Before treatment, immunohistochemistry was pMMR or genetic test was MSS.
4. ECOG performance status score of 0-1.
5. TNM staging of colon cancer by CT before surgery, confirmed to be T3, regardless of N; Rectal cancer was confirmed to be T3 by TNM staging by MRI before surgery, regardless of N. (TNM staging refers to the 8th edition of the AJCC/UICC TNM staging system for colorectal cancer)
6. Have not received systemic anti-tumor therapy for colorectal cancer in the past, including chemoradiotherapy, molecular targeted therapy, endocrine therapy, etc.
7. The following laboratory test values obtained before neoadjuvant therapy with appropriate organ function:
Routine blood count: hemoglobin value>=90g/L, white blood cell count>=3×10^9/L, neutrophil count>=3.0×10^9/L, platelet count>=5×10^9/L
Liver function: serum total bilirubin <=1.5× upper limit of normal (ULN), aspartate transferase <=2×ULN, alanine transferase <=3×ULN;
Renal function: serum creatinine <=1.5×ULN;
Coagulation function: prothrombin time <=1.5 ×ULN, activated partial thromboplastin time <=1.5×ULN
Cardiac function: left ventricular ejection fraction >50%
Thyroid function: normal.
8. Willing and able to comply with study protocols and visit schedules.

排除标准：

1.治疗前免疫组化检测为dMMR或基因检测结果为MSI-H；结直肠原发肿瘤无法完整切除。 2.全身 CT、MRI 或 PET-CT证实有远处转移（M1）。 3.患者合并梗阻、活动性出血或穿孔并且需行急诊手术或放置支架。 4.既往或同时存在其他活动性恶性肿瘤。 5.现有严重感染疾病或感染伤口不愈合。 6.参加研究前 12 个月内有活动性冠状动脉疾病，严重/不稳定性心绞痛或新确诊的心绞痛或心肌梗塞。 7.既往 6 个月内发生血栓或栓塞事件，例如脑血管意外（包括一过性脑缺血发作）、肺栓塞、深静脉血栓。 8.纽约心脏学会（NYHA）II 级或以上充血性心力衰竭。 9.已知存在人免疫缺陷病毒（HIV）感染或获得性免疫缺陷综合症（AIDS）相关性疾病。 10.存在活动性炎症性肠病或导致慢性腹泻的其他结直肠疾病。 11.存在任何既往治疗引起的，尚未消退的 CTCAE 2 级或以上毒性（贫血、脱发） 12.既往接受过任何研究性药物。 13.既往有输血史及器官移植史。 14.妊娠或哺乳期妇女。 15.既往有明确的神经或精神障碍史，包括癫痫或痴呆。 16.不稳定或会影响患者安全及其研究依从性的任何医学状况。

Exclusion criteria：

1. Before treatment, the immunohistochemical test was dMMR or the genetic test result was MSI-H; The primary colorectal tumor cannot be completely removed. 2. Whole-body CT, MRI, or PET-CT confirmed distant metastases (M1). 3. Patients with obstruction, active bleeding or perforation and need emergency surgery or stent placement. 4. Previous or concurrent presence of other active malignancies. 5. Existing serious infectious diseases or non-healing of infected wounds. 6. Active coronary artery disease, severe/unstable angina pectoris, or newly diagnosed angina pectoris or myocardial infarction within 12 months prior to study enrollment. 7. Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis within the past 6 months. 8. New York Heart Association (NYHA) Class II or above congestive heart failure. 9. Known presence of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related diseases. 10. Presence of active inflammatory bowel disease or other colorectal disease causing chronic diarrhea. 11. Presence of any prior therapy-induced CTCAE Grade 2 or above toxicity (anemia, alopecia) that has not resolved 12. Prior receipt of any investigational agent. 13. History of blood transfusion and organ transplantation in the past. 14. Pregnant or lactating women. 15. Have a clear history of neurological or psychiatric disorders, including epilepsy or dementia. 16. Unstable or any medical condition that would affect patient safety and their compliance with the study.

研究实施时间：

Study execute time：

从 From 2025-02-01 00:00:00至 To 2028-01-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-04-01 00:00:00 至 To 2026-01-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	68
Group：	Experimental group	Sample size：	68
干预措施：	卡瑞利珠单抗+mFOLFOX6	干预措施代码：
Intervention：	Camrelizumab + mFOLFOX6	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	贵州省	市(区县)：	贵阳
Country：	China	Province：	Guizhou Province	City：	Guiyang
单位(医院)：	贵州医科大学附属医院	单位级别：	三甲
Institution hospital：	The Affiliated Hospital of Guizhou Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	术后病理缓解率	指标类型：	主要指标
Outcome：	Postoperative pathological remission rate(MPR+PR)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	3年无病生存率	指标类型：	次要指标
Outcome：	3-year Disease 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：	3年总生存时间	指标类型：	次要指标
Outcome：	3-year 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：	病理完全缓解率	指标类型：	次要指标
Outcome：	Pathologic Complete Response	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	肿瘤降期（包括肿瘤直径、肿瘤分期、淋巴结状态、TRG分级）	指标类型：	次要指标
Outcome：	Tumor downstaging (including tumor diameter, tumor stage, lymph node status, TRG grade)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	围手术期并发症	指标类型：	次要指标
Outcome：	Perioperative complications	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：	结肠癌组织
Sample Name：	Blood	Tissue：	Colon cancer 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)：

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：	无
Blinding：	None
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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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, 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：	2025-03-31 16:31:13