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：	ChiCTR2300067311
最近更新日期： Date of Last Refreshed on：	2023-05-08 21:18:38
注册时间： Date of Registration：	2023-01-04 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	单细胞测序鉴定口腔鳞癌分子切缘的前瞻队列研究
Public title：	Single-cell sequencing identifies molecular margins of oral squamous cell carcinoma: a prospective cohort study
注册题目简写：
English Acronym：
研究课题的正式科学名称：	单细胞测序鉴定口腔鳞癌分子切缘的前瞻队列研究
Scientific title：	Single-cell sequencing identifies molecular margins of oral squamous cell carcinoma: a prospective cohort 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：	朱桂全	研究负责人：	朱桂全
Applicant：	Guiquan Zhu	Study leader：	Guiquan Zhu
申请注册联系人电话： Applicant telephone：	+86 15902891530	研究负责人电话： Study leader's telephone：	+86 15902891530
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：	zhugq@scu.edu.cn	研究负责人电子邮件： Study leader's E-mail：	zhugq@scu.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：	四川省成都市武侯区成都市武侯区人民南路三段14号	研究负责人通讯地址：	四川省成都市武侯区成都市武侯区人民南路三段14号
Applicant address：	14 Section 3, Renmin South Road, Wuhou District, Chengdu, Sichuan, China	Study leader's address：	14 Section 3, Renmin South Road, Wuhou District, Chengdu, Sichuan, 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：	四川大学华西口腔医院
Applicant's institution：	West China Hospital of Stomatology, Sichuan University
研究负责人所在单位：	四川大学华西口腔医院
Affiliation of the Leader：	West China Hospital of Stomatology, Sichuan 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：	WCHSIRB-D-2021-216-R1	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：	四川大学华西口腔医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of West China Hospital of Stomatology, Sichuan University
伦理委员会批准日期： Date of approved by ethic committee：	2022-12-29 00:00:00
伦理委员会联系人：	李伟
Contact Name of the ethic committee：	Wei Li
伦理委员会联系地址：	四川省成都市武侯区成都市武侯区人民南路三段14号
Contact Address of the ethic committee：	14 Section 3, Renmin South Road, Wuhou District, Chengdu, Sichuan, 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：

四川大学华西口腔医学院

Primary sponsor：

West China Hospital of Stomatology, Sichuan University

研究实施负责（组长）单位地址：

四川省成都市武侯区成都市武侯区人民南路三段14号

Primary sponsor's address：

14 Section 3, Renmin South Road, Wuhou District, Chengdu, Sichuan, 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)：	四川	市(区县)：	成都
Country：	China	Province：	Sichuan	City：	Chengdu
单位(医院)：	四川大学华西口腔医院	具体地址：	武侯区成都市武侯区人民南路三段14号
Institution hospital：	West China Hospital of Stomatology, Sichuan University	Address：	14 Section 3, Renmin South Road, Wuhou District

经费或物资来源：

四川大学华西口腔医院临床医学研究项目

Source(s) of funding：

Clinical Medicine Research Project of West China l Hospital of Stomatology, Sichuan University

研究疾病：

口腔鳞状细胞癌

Target disease：

Oral squamous cell carcinoma

研究疾病代码：

Target disease code：

研究类型：

预后研究

Study type：

Prognosis study

研究所处阶段：

探索性研究/预试验

Study phase：

0

研究设计：

队列研究

Study design：

Cohort study

研究目的：

绘制口腔鳞癌手术阴性切缘单细胞分子图谱，建立切缘单细胞分子图谱与口腔癌患者5年生存率、局部控制率的相关性；鉴定出能够预测口腔鳞癌患者不良预后的单细胞基因（组合），建立口腔鳞癌预后预测模型。

Objectives of Study：

1. To depict a single-cell molecular atlas of negative surgical margins of oral squamous cell carcinoma, and reveal the correlation between the single-cell molecular landscape and the 5-year survival rate and local control rate of patients with oral cancer; 2. To identify single-cell gene signatures that can predict the prognosis of patients with oral squamous cell carcinoma and establish prognostic model.

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. Age >= 18 years old and <= 75 years old, regardless of gender;
2. Oral squamous cell carcinoma patients who are pathologically confirmed and meet the following conditions:
(1) Newly diagnosed patients with stage III-IVa oral squamous cell carcinoma without distant metastasis;
(2) Surgical resection is possible after evaluation by head and neck surgery;
(3) Willing to accept surgical treatment;
3. Eastern Cooperative Oncology Group (ECOG) physical status score is 0-1;
4. Have adequate organ and bone marrow function, as defined below:
(1) Blood routine: neutrophil count (NEUT) >= 1.5 × 10^9/L; platelet (PLT) >= 100 × 10^9/L; hemoglobin >= 9 g/dL;
(2) Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) <= 2.5 × upper limit of normal (ULN); total bilirubin (TBIL) <= 2 × ULN;
(3) Albumin >= 2.8 g/dL;
(4) Renal function: creatinine clearance rate (CCR) > 60 ml/min;
(5) Coagulation function: international normalized ratio (INR) ≤ 1.5; partial thromboplastin time (APTT) <= 1.5 × ULN;
5. The subjects voluntarily joined the study, signed the informed consent form, and were able to abide by the visits and related procedures stipulated in the protocol.

排除标准：

1. 其它恶性肿瘤病史（已治愈的且5年内未复发的非黑色素瘤原位皮肤癌、浅表性膀胱癌、原位宫颈癌、胃肠道粘膜内癌、乳腺癌、局限性前列腺癌等研究者认为可以入组的恶性肿瘤史除外）； 2. 任何活动性自身免疫病或有自身免疫病病史，包括但不限于与免疫有关的神经疾病、多发性硬化症、自身免疫性（脱髓鞘）神经病、格林巴利综合症、重症肌无力、系统性红斑狼疮（SLE）、结缔组织疾病、硬皮病、炎症性肠病包括克罗恩病和溃疡性结肠炎、自身免疫性肝炎、中毒性表皮坏死松解症（TEN）或Stevens-Johnson综合征（使用稳定剂量的胰岛素的Ⅰ型糖尿病除外）； 3. 有过敏性疾病、严重药物过敏史、已知对大分子蛋白制剂过敏者（注：严重过敏指导致住院的过敏）； 4. 接受过以下任何治疗： (1) 既往使用过化疗药物、PD-1抗体、PD-L1抗体、PD-L2抗体、CTLA-4抗体或EGFR抗体的患者； (2) 接种过抗肿瘤疫苗者； (3) 首次给药前4周内或计划在研究期间内使用任何抗感染性疾病的活性疫苗（如流感疫苗，水痘疫苗等）； (4) 首次给药前4周内接受过大手术或有严重外伤； (5) 既往抗肿瘤治疗毒性未恢复至≤ CTCAE 5.0版1级（脱发、既往铂类治疗相关神经毒性的后遗症除外）或入组/排除标准规定的水平； 5. 伴有严重的内科疾病者，如Ⅱ级及以上心功能异常（NYHA标准）、缺血性心脏病（如心肌梗死或心绞痛）、有临床意义的室上性或室性心律失常、控制不佳的糖尿病（空腹血糖≥ 10 mmol/L），控制不佳的高血压（收缩压> 150 mmHg和/或舒张压> 100 mmHg），超声心动图显示射血分数< 50%；QTc间期，男性> 450 msec，女性> 470 msec；心电图检查异常且研究者认为对试验药物有额外风险； 6. 已知间质性肺炎病史、非感染性肺炎病史或高度怀疑有间质性肺炎的受试者；或可能会干扰可疑的药物相关肺毒性的检测或处理的受试者；允许既往曾有药源性或放射性非感染性肺炎但无症状的受试者入组；有活动性肺结核，或既往有肺结核感染史但经治疗未控制者； 7. 甲状腺功能亢进症的患者和患有器质性甲状腺疾病的患者不能入组，用甲状腺替代激素治疗可以控制的甲状腺功能减退症可以入组（是否可以控制由研究者和/或内分泌科确认）； 8. 有活动性感染，或者在筛选期间、首次给药前48 h内发生原因不明的发热，或者签署知情同意前1周内使用全身性抗生素； 9. 受试者存在活动性乙型肝炎（HBV DNA≥ 2000 IU/ml或104拷贝数/ml）或丙型肝炎（丙肝抗体阳性，且HCV RNA高于分析方法的检测下限），或已知有人类免疫缺陷病毒（HIV）检查阳性病史或已知有获得性免疫缺陷综合征（艾滋病）； 10. 既往有明确的神经或精神障碍史，如癫痫或痴呆； 11. 有明确药物滥用史或3个月内有酒精滥用史

Exclusion criteria：

1. History of other malignant tumors (non-melanoma skin cancer in situ, superficial bladder cancer, cervical cancer in situ, gastrointestinal mucosal cancer, breast cancer, localized prostate cancer, etc. that have been cured and have not recurred within 5 years) except for the history of malignant tumors that the investigator believes can be included); 2. Any active autoimmune disease or history of autoimmune disease, including but not limited to immune-related neurological diseases, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis , systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis (TEN) or Stevens- Johnson syndrome (except type 1 diabetes on stable doses of insulin); 3. People with allergic diseases, history of severe drug allergy, known allergy to macromolecular protein preparations (Note: severe allergy refers to allergy leading to hospitalization); 4. Received any of the following treatments: (1) Patients who have used chemotherapy drugs, PD-1 antibody, PD-L1 antibody, PD-L2 antibody, CTLA-4 antibody or EGFR antibody in the past; (2) Those who have been vaccinated with anti-tumor vaccines; (3) Any active vaccine against infectious diseases (such as influenza vaccine, chickenpox vaccine, etc.) used within 4 weeks before the first administration or planned to be used during the study period; (4) Have undergone major surgery or severe trauma within 4 weeks before the first administration; (5) The toxicity of the previous anti-tumor therapy has not recovered to the level specified in the inclusion/exclusion criteria; 5. Those with serious medical diseases, such as grade II and above cardiac dysfunction (NYHA standard), ischemic heart disease (such as myocardial infarction or angina pectoris), clinically significant supraventricular or ventricular arrhythmia, controlled Poor diabetes (fasting blood glucose >= 10 mmol/L), poorly controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg), echocardiogram showed ejection fraction < 50%; QTc interval, male > 450 msec, women > 470 msec; abnormal electrocardiogram and the investigator believes that there is an additional risk to the trial drug; 6. Subjects with a known history of interstitial pneumonia, non-infectious pneumonia, or highly suspected interstitial pneumonia; or subjects who may interfere with the detection or treatment of suspected drug-related pulmonary toxicity; Subjects with drug-induced or radiation-induced non-infectious pneumonia but asymptomatic subjects were enrolled; those with active pulmonary tuberculosis, or those who had a history of tuberculosis infection in the past but were not controlled after treatment; 7. Patients with hyperthyroidism and patients with organic thyroid disease cannot be enrolled, and hypothyroidism that can be controlled by thyroid replacement hormone therapy can be enrolled (whether it can be controlled is confirmed by the investigator and/or the Department of Endocrinology) ); 8. Active infection, or unexplained fever during the screening period and within 48 hours before the first administration, or use of systemic antibiotics within 1 week before signing the informed consent; 9. The subject has active hepatitis B (HBVDNA >= 2000 IU/ml or 104 copies/ml) or hepatitis C (hepatitis C antibody positive, and HCV RNA is higher than the detection limit of the analytical method), or known human immune Positive medical history of deficient virus (HIV) or known acquired immunodeficiency syndrome (AIDS); 10. There is a clear history of neurological or mental disorders in the past, such as epilepsy or dementia; 11. There is a clear history of drug abuse or alcohol abuse within 3 months

研究实施时间：

Study execute time：

从 From 2023-01-31 00:00:00至 To 2026-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-01-31 00:00:00 至 To 2023-05-31 00:00:00

干预措施：

Interventions：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	四川	市(区县)：	成都
Country：	China	Province：	Sichuan	City：	Chengdu
单位(医院)：	四川大学华西口腔医学院	单位级别：	三甲
Institution hospital：	West China Hospital of Stomatology, Sichuan University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	总生存期	指标类型：	主要指标
Outcome：	Overall survival	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	无病生存期	指标类型：	主要指标
Outcome：	Disease-free survival	Type：	Primary 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：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	组织	组织：	口腔鳞癌肿瘤切缘
Sample Name：	human tissue	Tissue：	surgical margin of oral squamous cell carcinoma
人体标本去向	使用后保存	说明	制作病理玻片及单细胞悬液
Fate of sample：	Preservation after use	Note：	Making pathology slides and single cell solution

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）：

不适用

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

N/A

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）：	研究进行中
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The research in progress
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：	本研究采用纸质版病例记录表(Case Record Form, CRF) 及电子病例报告表（electronic case report form, eCRF）进行临床试验数据管理。整个数据管理过程将按照国家现行相关法律法规和指导原则、数据管理计划（data management plan, DMP）以及相关数据管理SOP执行。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	In this study, paper version of Case Record Form (CRF) and electronic case report form (eCRF) will be used for clinical trial data management. The entire data management process will be implemented in accordance with the current relevant national laws, regulations and guiding principles, data management plan (DMP) and relevant data management SOPs.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2023-01-04 10:30:45