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：	ChiCTR2000037950
最近更新日期： Date of Last Refreshed on：	2020-11-15 16:29:11
注册时间： Date of Registration：	2020-09-06 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	PD-1联合新辅助化疗在Ⅲ期非小细胞肺癌的临床研究
Public title：	Clinical study of PD-1 combined with neoadjuvant chemotherapy in stage III non-small cell lung cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	PD-1联合新辅助化疗在Ⅲ期非小细胞肺癌的临床研究
Scientific title：	Clinical study of PD-1 combined with neoadjuvant chemotherapy in stage III non-small cell lung 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：	白悦	研究负责人：	白悦
Applicant：	Bai Yue	Study leader：	Bai Yue
申请注册联系人电话： Applicant telephone：	+86 18394426300	研究负责人电话： Study leader's telephone：	+86 18394426300
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：	surrealby@163.com	研究负责人电子邮件： Study leader's E-mail：	surrealby@163.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：	甘肃省兰州市七里河区小西湖东街2号	研究负责人通讯地址：	甘肃省兰州市七里河区小西湖东街2号
Applicant address：	2 Xiaoxihu Street East, Qilihe District, Lanzhou, Gansu, China	Study leader's address：	2 Xiaoxihu Street East, Qilihe District, Lanzhou, Gansu, 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：	甘肃省肿瘤医院
Applicant's institution：	Gansu Cancer Hospital
研究负责人所在单位：	甘肃省肿瘤医院
Affiliation of the Leader：	Gansu Cancer Hospital

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：	A202005140031	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：	甘肃省医学科学研究院
Name of the ethic committee：	Gansu Academy of Medical Sciences
伦理委员会批准日期： Date of approved by ethic committee：	2020-05-14 00:00:00
伦理委员会联系人：	王军
Contact Name of the ethic committee：	Wang Jun
伦理委员会联系地址：	甘肃省兰州市七里河区小西湖东街2号
Contact Address of the ethic committee：	2 Xiaoxihu Street East, Qilihe District, Lanzhou, Gansu, 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：

甘肃省肿瘤医院

Primary sponsor：

Gansu Cancer Hospital

研究实施负责（组长）单位地址：

甘肃省兰州市七里河区小西湖东街2号

Primary sponsor's address：

2 Xiaoxihu Street East, Qilihe District, Lanzhou, Gansu, 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)：	甘肃	市(区县)：	兰州
Country：	China	Province：	Gansu	City：	Lanzhou
单位(医院)：	甘肃省肿瘤医院	具体地址：	七里河区小西湖东街2号
Institution hospital：	Gansu Cancer Hospital	Address：	2 Xiaoxihu Street East, Qilihe District

经费或物资来源：

甘肃省卫生健康委员会

Source(s) of funding：

Gansu Provincial Health Commission

研究疾病：

肺癌

Target disease：

Lung 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：

上市后药物

Study phase：

4

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

通过免疫治疗与新辅助化疗相结合的方法治疗Ⅲ期非小细胞肺癌，使部分单纯新辅助化疗后无法手术的患者得到手术治疗的机会，提高手术切除率，改善Ⅲ期非小细胞肺癌患者的生存期。

Objectives of Study：

Treat stage III non-small cell lung cancer through a combination of immunotherapy and neoadjuvant chemotherapy, so that some patients who are inoperable after neoadjuvant chemotherapy alone can receive surgical treatment, increase the surgical resection rate, and improve the treatment of patients with stage III non-small cell lung cancer Lifetime.

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. Male and female patients aged 18 to 70 years;
2. Patients with ECoG score of 0-2;
3. Patients with an expected survival time of no less than 12 weeks;
4. Patients with non-small cell lung cancer (NSCLC) with negative driving gene confirmed by pathology (histology or cytology) (according to WHO classification 2015);
5. According to the eighth edition of TNM staging, the subjects were resectable stage ii-iiib (IIIB only t3n2) NSCLC;
6. Patients with measurable lesions (according to RECIST 1.1 standard, the long diameter of tumor lesions >=10 mm, and the short diameter of lymph node lesions >= 15 mm);
7. Patients without radiotherapy, chemotherapy, surgery and targeted therapy before enrollment;
8. Subjects must have sufficient lung function for the expected pneumonectomy;
9. Patients with normal main organ function meet the following criteria:
(1) The blood routine examination standard should meet the following requirements:
ANC >= 1.5 x 10^9/L;
PLT >= 100 x 10^9/L;
HB >= 90g/L;
(2) Biochemical examination should meet the following standards:
TBIL <= 1.5 ULN
ALT and AST < 2.5 ULN, ALT and AST < 5 ULN in patients with liver metastasis;
Bun and Cr <= 1.5 ULN or creatinine clearance rate >= 50 ml/min (Cockcroft Gault formula);
(3) Coagulation function should be in accordance with INR <= 1.5 and APTT <= 1.5 ULN;
10. Women of childbearing age were required to have a serum pregnancy test within 3 days before the start of the study, and the results were negative, and they were willing to use a medically recognized high-efficiency contraceptive method (such as intrauterine device, contraceptive or condom) during the study period and within 3 months after the last administration of the study drug; for male subjects whose partners were women of childbearing age, surgical sterilization was required, Or agree to use effective contraceptive methods during the study and within 3 months after the last study administration;
11. The subjects volunteered to join the study and signed the informed consent. They had good compliance and cooperated with the follow-up.

排除标准：

1）有症状的中枢神经系统转移；
2）患有任何活动性自身免疫疾病或自身免疫疾病史（如下，但不局限于：间质性肺炎、葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、心肌炎、肾炎、甲状腺功能亢进、甲状腺功能降低（激素替代治疗后可纳入））；患有白癜风或童年期哮喘已完全缓解且成人后无需任何干预可纳入；需要支气管扩张剂进行医学干预的患者则不可纳入；
3）患有先天或后天免疫功能缺陷，如人类免疫缺陷病毒（HIV）感染者，活动性乙型肝炎（HBV DNA ≥ 500 IU/mL），丙型肝炎（丙肝抗体阳性，且HCV-RNA高于分析方法的检测下限）或合并乙肝和丙肝共同感染；
4）首次使用研究药物前14天之内使用过免疫抑制药物，不包括喷鼻和吸入性皮质类固醇或生理剂量的系统性类固醇激素（即不超过10 mg/天泼尼松或其等效药物）；
5）首次给药前4周内或计划在研究期间接种减毒活疫苗；
6）过去3年内罹患其他恶性肿瘤；
7）有证据显示既往或目前有肺纤维化、间质性肺炎、尘肺、放射学肺炎、药物所致的肺炎以及肺功能严重受损等；
8）无法控制的高血压（收缩压≥140 mmHg 或者舒张压≥90 mmHg，尽管进行了最佳药物治疗）；
9）患有II级以上心肌缺血或心肌梗塞、控制不良的心律失常（包括 QTc间期男性≥450ms、女性≥470ms）。按NYHA标准，III～Ⅳ级心功能不全，或心脏彩超检查提示左室射血分数（LVEF）＜50%者入组前6个月内发生过心肌梗死，纽约心脏学会II级或以上心力衰竭，未得到控制的心绞痛，未得到控制的严重室性心律失常，有临床意义的心包疾病，或者心电图提示急性缺血或活动性传导系统异常；
10）首次用药前4周内并发重度感染（如：需要静脉滴注抗生素、抗真菌或抗病毒药物），或在筛选期间/首次给药前出现不明原因的发热>38.5°C；
11）已知异体器官移植史或异体造血干细胞移植史；
12）怀孕或哺乳期妇女；有生育能力的患者不愿或无法采取有效的避孕措施者；
13）已知对卡瑞利珠单抗、白蛋白紫杉醇或其辅料会产生变态反应、超敏反应或不耐受；
14）正在参加其他临床研究或首次用药时间距离前一次临床研究结束（末次用药）时间少于4周，或该研究药物的5个半衰期的受试者；
15）受试者已知有精神类药物滥用、酗酒或吸毒史；
16）研究者认为存在可能损害受试者或者导致受试者无法满足或执行研究要求的任何状况。

Exclusion criteria：

1. Symptomatic patients with central nervous system metastasis;
Two Patients with any history of active autoimmune disease or autoimmune disease (as follows, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (which can be included after hormone replacement therapy)); patients with vitiligo or childhood asthma have been completely relieved and have no adult Patients who need any intervention can not be included;
3. Patients with congenital or acquired immune deficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV DNA >= 500 IU / ml), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the detection limit of the analysis method) or combined with hepatitis B and hepatitis C co infection;
4. Patients who had used immunosuppressive drugs within 14 days before the first use of the study drug did not include nasal and inhaled corticosteroids or physiological doses of systemic steroids (i.e. prednisone or its equivalent not exceeding 10 mg / day);
5. Patients who received live attenuated vaccine within 4 weeks before the first administration or during the study period;
6. Patients with other malignant tumors in the past three years;
7. Patients with previous or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiologic pneumonia, drug-induced pneumonia and severe impairment of lung function;
8. Patients with uncontrolled hypertension (systolic blood pressure >=140 mmHg or diastolic blood pressure >=90 mmHg, despite the best drug treatment);
9. Patients with myocardial ischemia or myocardial infarction of grade II or above and arrhythmias with poor control (including QTc interval >= 450ms in males and >= 470ms in females). According to NYHA criteria, patients with grade III to IV cardiac insufficiency or with left ventricular ejection fraction (LVEF) less than 50% by echocardiography had myocardial infarction, NYHA grade II or above heart failure, uncontrolled angina pectoris, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or acute ischemia or live as indicated by ECG Abnormal conduction system;
10. Patients with severe infection within 4 weeks before the first medication (e.g. intravenous drip of antibiotics, antifungal or antiviral drugs), or fever of unknown origin > 38.5 degree C during screening / before first administration;
11. Patients with known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
12. Pregnant or lactating women; fertile patients who are unwilling or unable to take effective contraceptive measures;
13. Patients who are known to have allergic reaction, hypersensitivity or intolerance to calicizumab, albumin paclitaxel or their excipients;
14. Subjects who are participating in other clinical studies or taking the first medication for less than 4 weeks from the end of the previous clinical study (the last medication), or 5 half-life of the study drug;
15. Patients with known history of psychotropic substance abuse, alcoholism or drug use;
16. The researcher believes that there are any conditions that may damage the subjects or cause the subjects to be unable to meet or perform the research requirements.

研究实施时间：

Study execute time：

从 From 2020-05-30 00:00:00至 To 2021-12-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2020-09-15 00:00:00 至 To 2021-12-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	15
Group：	Experimental group	Sample size：	15
干预措施：	卡瑞利珠单抗+化疗	干预措施代码：
Intervention：	PD-1+chemotherapy	Intervention code：

组别：	对照组	样本量：	15
Group：	control group	Sample size：	15
干预措施：	化疗	干预措施代码：
Intervention：	chemotherapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	甘肃	市(区县)：	兰州
Country：	China	Province：	Gansu	City：	Lanzhou
单位(医院)：	甘肃省肿瘤医院	单位级别：	三甲
Institution hospital：	Gansu Cancer Hospital	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：	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：	降期后的手术率	指标类型：	主要指标
Outcome：	Surgical rate after downgrade	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	病理显著缓解率	指标类型：	主要指标
Outcome：	MPR	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	不良反应	指标类型：	次要指标
Outcome：	Adverse reactions	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	手术并发症	指标类型：	次要指标
Outcome：	Surgical 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：
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：	尿液	组织：
Sample Name：	urine	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：

正在进行

Recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	70	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）：

采用SPSS 25.0生成随机表，以随机分配表作为总盲底，将符合入组条件的受试者按照先后顺序分配随机表上的组别，进入试验组和对照组。该随机分配表具有重现性。

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

SPSS 25.0 is used to generate a random table, and the random allocation table is used as the total blind base. The subjects who meet the conditions for entry are assigned to the groups on the random table in order and entered the experimental group and the control group.

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：	未说明
Blinding：	Not stated
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）：	文章发表
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Published Article
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：	CRF
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：	2020-09-06 22:22:48