ChiCTR2100049012 版本V1.0 版本创建时间2022/02/25 16:03:16 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2100049012 

最近更新日期：

Date of Last Refreshed on：

2021-07-19 15:24:50 

注册时间：

Date of Registration：

2021-07-19 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

请与我们联系上传伦理批件。 卡瑞利珠单抗联合化疗用于可切除局部晚期非小细胞肺癌新辅助+辅助治疗的 单臂、单中心、Ⅱ期临床研究

Public title：

Single-arm, single-center, phase II clinical study of camrelizumab combined with chemotherapy for neoadjuvant + adjuvant therapy in resectable locally advanced non-small cell lung cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

卡瑞利珠单抗联合化疗用于可切除局部晚期非小细胞肺癌新辅助+辅助治疗的 单臂、单中心、Ⅱ期临床研究

Scientific title：

Single-arm, single-center, phase II clinical study of camrelizumab combined with chemotherapy for neoadjuvant + adjuvant therapy in resectable locally advanced 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：

程丹丹 

研究负责人：

陈军 

Applicant：

Cheng Dandan 

Study leader：

Chen Jun 

申请注册联系人电话：

Applicant telephone：

15822192921

研究负责人电话：

Study leader's telephone：

15822192921

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：

1257406295@qq.com

研究负责人电子邮件：

Study leader's E-mail：

1257406295@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：

天津市和平区鞍山道154号

研究负责人通讯地址：

天津市和平区鞍山道154号

Applicant address：

No. 154, Anshan Road, Heping District, Tianjin

Study leader's address：

No. 154, Anshan Road, Heping District, Tianjin

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：

天津医科大学总医院

Applicant's institution：

Tianjin Medical University General Hospital

研究负责人所在单位：

Affiliation of the Leader：

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

IRB2021-YX-030-01

伦理委员会批件附件：

Approved file of Ethical Committee：

批准本研究的伦理委员会名称：

天津医科大学总医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Tianjin Medical University General Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2013-08-26 00:00:00

伦理委员会联系人：

王一

Contact Name of the ethic committee：

Wang Yi

伦理委员会联系地址：

天津市和平区鞍山道154号

Contact Address of the ethic committee：

No. 154, Anshan Road, Heping District, Tianjin

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：

天津医科大学总医院

Primary sponsor：

Tianjin Medical University General Hospital

研究实施负责（组长）单位地址：

天津市和平区鞍山道154号

Primary sponsor's address：

No. 154, Anshan Road, Heping District, Tianjin

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

天津

市(区县)：

Country：

China

Province：

Tianjin

City：

单位(医院)：

天津医科大学总医院

具体地址：

和平区鞍山道154号

Institution
hospital：

Tianjin Medical University General Hospital

Address：

154 Anshan Road, Heping District

经费或物资来源：

无

Source(s) of funding：

none

Target disease：

lung cancer

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：

横断面 

Study design：

Cross-sectional 

研究目的：

评价卡瑞利珠单抗联合化疗用于可切除局部晚期非小细胞肺癌的有效性及安全性  

Objectives of Study：

To evaluate the effectiveness and safety of camrelizumab combined with chemotherapy for resectable locally advanced non-small cell lung cancer

药物成份或治疗方案详述：

术前新辅助卡瑞利珠单抗+化疗治疗两周期，术后辅助卡瑞利珠单抗+化疗治疗两周期，辅助后卡瑞利珠单抗维持治疗12周期 

Description for medicine or protocol of treatment in detail：

Two cycles of neoadjuvant camrelizumab + chemotherapy before surgery, two cycles of adjuvant camrelizumab + chemotherapy after surgery, and 12 cycles of maintenance treatment with camrelizumab after adjuvant 

纳入标准：

1）入组前签署书面知情同意书；
2）年龄18-70岁，男女均可；
3）治疗前评估可手术切除患者：①病理学和影像学确诊的可切除非小细胞肺癌患者（临床Ⅲa期，IASLC/UICC第八版肺癌TNM分期），②研究者认为经过新辅助治疗后有手术希望的受试者（临床Ⅲb期，IASLC/UICC第八版肺癌TNM分期），注：经PET/CT、EBUS/EUS或纵隔镜进行淋巴结分期；
4）基因检测EGFR（-），ALK（-），ROS（-）；
5）具有可测量的病灶，（根据RECIST 1.1标准，肿瘤病灶CT扫描长径≥10mm，淋巴结病灶CT扫描短径≥15mm；）；
6）ECOG PS评分：0～1；
7）预期生存期大于6个月；
8）重要器官的功能符合下列要求（不包括在14天内用任何血液成分及细胞生长因子）：
血常规：
中性粒细胞≥1,500/mm3
血小板计数≥100,000/mm3
血红蛋白≥5.6 mmol/L (9g/dL)；
肝肾功能：
血清肌酐(SCr) ≤ 1.5倍正常值上限（ULN）或肌酐清除率≥50 ml/min（Cockcroft-Gault公式）；
总胆红素（TBIL）≤ 1.5倍正常值上限（ULN）；
谷草转氨酶（AST）或谷丙转氨酶（ALT）水平≤ 2.5倍正常值上限（ULN）； 尿蛋白<2+；如果尿蛋白≥2+，则24小时尿蛋白定量显示蛋白质必须≤1g；
9）凝血功能正常，无活动性出血和血栓形成疾病
a. 国际标准化比值INR≤1.5×ULN；
b. 部分凝血活酶时间APTT≤1.5×ULN；
c. 凝血酶原时间PT≤1.5ULN；
10) 非手术绝育或育龄期女性患者，需要在研究治疗期间和研究治疗期结束后3个月内采用一种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套）；非手术绝育的育龄期女性患者在研究入组前的7 天内血清或尿HCG检查必须为阴性；而且必须为非哺乳期； 非手术绝育或育龄期男性患者，需要同意与其配偶在研究治疗期间和研究治疗期结束后3个月内采用一种经医学认可的避孕措施。
11) 受试者自愿加入本研究，依从性好，配合安全性和生存期随访。

Inclusion criteria

1) Sign a written informed consent before joining the group;
2) 18-70 years old, both male and female;
3) Evaluation of resectable patients before treatment: ①Resectable non-small cell lung cancer patients diagnosed by pathology and imaging (Clinical stage IIIa, IASLC/UICC eighth edition lung cancer TNM staging), ②The investigator believes that after neoadjuvant treatment Subjects who are promising for surgery (clinical stage IIIb, IASLC/UICC eighth edition lung cancer TNM staging), note: lymph node staging by PET/CT, EBUS/EUS or mediastinoscopy;
4) Genetic testing of EGFR (-), ALK (-), ROS (-);
5) With measurable lesions, (according to the RECIST 1.1 standard, the long diameter of the CT scan of tumor lesions is ≥10mm, and the short diameter of CT scan of lymph node lesions is ≥15mm;);
6) ECOG PS score: 0～1;
7) The expected survival period is greater than 6 months;
8) The functions of vital organs meet the following requirements (not including the use of any blood components and cell growth factors within 14 days):
Blood routine:
Neutrophils ≥1,500/mm3
Platelet count ≥100,000/mm3
Hemoglobin ≥5.6 mmol/L (9g/dL);
Liver and kidney function:
Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula);
Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤ 2.5 times the upper limit of normal (ULN); urine protein <2+; if urine protein ≥ 2+, the 24-hour urine protein quantitative display protein must be ≤ 1g;
9) The coagulation function is normal, without active bleeding and thrombosis
a. International standardized ratio INR≤1.5×ULN;
b. Partial thromboplastin time APTT≤1.5×ULN;
c. Prothrombin time PT≤1.5ULN;
10) Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as intrauterine device, contraceptive or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative for serum or urine HCG within 7 days before enrollment in the study; and must be non-lactating; male patients of childbearing age who are not surgically sterilized or childbearing age must agree with their spouse during the study treatment period and the study Use a medically approved contraceptive method within 3 months after the end of the treatment period.
11) Subjects voluntarily join the study, with good compliance, and cooperation with safety and survival follow-up.

排除标准：

1）先前接受放疗、化疗、激素治疗、手术或分子靶向治疗；
2）影像学证实有远处转移患者；
3）受试者既往或同时患有其它恶性肿瘤（已治愈的皮肤基底细胞癌和宫颈原位癌除外）；
4）既往曾行卡瑞利珠单抗或其他PD-1/PD-L1治疗不能入组；已知受试者既往对大分子蛋白制剂，或已知对任何卡瑞利珠单抗、或受试者新辅助治疗期间应用的化疗用药成分过敏；
5）受试者存在任何活动性自身免疫病或有自身免疫病病史（如以下，但不局限于：自身免疫性肝炎、间质性肺炎，葡萄膜炎，肠炎，肝炎，垂体炎，血管炎，肾炎，甲状腺功能亢进，甲状腺功能降低，既往曾接受过甲状腺手术者不能纳入；受试者患有白癜风或在童年期哮喘已完全缓解，成人后无需任何干预的可纳入；受试者需要支气管扩张剂进行医学干预的哮喘则不能纳入）；
6）受试者正在使用免疫抑制剂、或全身、或可吸收的局部激素治疗以达到免疫抑制目的（剂量>10mg/天泼尼松或其他等疗效激素），并在入组前2周内仍在继续使用的；
7）有临床症状的腹水或胸腔积液，需要治疗性的穿刺或引流；
8）有未能良好控制的心脏临床症状或疾病，如：（1）NYHA2级以上心力衰竭（2）不稳定型心绞痛（3）1年内发生过心肌梗死（4）有临床意义的室上性或室性心律失常需要治疗或干预的患者；
9）凝血功能异常（PT>16s、APTT>43s、TT>21s、Fbg>2g/L），具有出血倾向或正在接受溶栓或抗凝治疗；
10）既往或目前有严重的出血（3个月内出血>30 ml）、咯血（4周内>5 ml的新鲜血液）或者12月内发生血栓栓塞事件（包括卒中事件和/或短暂性脑缺血发作）；
11）受试者入组前2周内仍在使用中药免疫调节剂；
12）受试者有活动性感染或在筛选期间、首次给药前发生原因不明发热>38.5度（经研究者判断，受试者因肿瘤产生的发热可以入组）；
13）既往和目前有肺纤维化史、间质性肺炎、尘肺、放射性肺炎、药物相关肺炎、肺功能严重受损等的客观证据的患者；
14）受试者先天或后天免疫功能缺陷，如HIV感染者，或活动性肝炎（转氨酶不符合入选标准，乙肝参考： HBV DNA≥10?/ml；丙肝参考： HCV RNA≥103/ml）；慢性乙型肝炎病毒携带者，HBV DNA＜2000 IU/ml（<104拷贝/ml），试验期间必须同时接受抗病毒治疗才可以入组；
15）受试者正在参加其他临床研究或距离前一项临床研究结束不足1个月；受试者在研究期间可能会接受其他全身抗肿瘤治疗；
16）研究用药前不足4周内或可能于研究期间接种活疫苗；
17）受试者已知有精神类药物滥用、酗酒或吸毒史；
18）受试者首次治疗前4周内接受过中药治疗；
19）受试者无法或不同意负担自费部分的检查和治疗费用，除外临床研究药品，联合化疗和与临床研究药品联合化疗相关的SAE；
20）研究者认为应排除在本研究之外，例如经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素，如，其他的严重疾病（含精神疾病）需要合并治疗，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到受试者的安全，或资料及样品的收集。

Exclusion criteria：

1) Previously received radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy;
2) Imaging confirmed patients with distant metastases;
3) The subject has previously or simultaneously suffered from other malignant tumors (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
4) Previously received camrelizumab or other PD-1/PD-L1 treatments and cannot be included in the group; the subject is known to have been exposed to macromolecular protein preparations, or is known to be against any camrelizumab, or Subjects are allergic to the chemotherapeutic ingredients used during neoadjuvant treatment;
5) The subject has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis , Nephritis, hyperthyroidism, decreased thyroid function, those who have previously undergone thyroid surgery cannot be included; subjects who have vitiligo or asthma in childhood have been completely relieved, and those who do not need any intervention after adults can be included; subjects need bronchial tubes Dilators for medical intervention of asthma cannot be included);
6) Subjects are using immunosuppressive agents, or systemic or absorbable local hormone therapy to achieve immunosuppressive purposes (dose>10mg/day prednisone or other curative hormones), and within 2 weeks before enrollment Still in use;
7) Ascites or pleural effusion with clinical symptoms requires therapeutic puncture or drainage;
8) Uncontrolled cardiac clinical symptoms or diseases, such as: (1) NYHA level 2 or higher heart failure (2) Unstable angina (3) Myocardial infarction occurred within 1 year (4) Supraventricular with clinical significance Or patients with ventricular arrhythmia in need of treatment or intervention;
9) Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg>2g/L), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy;
10) Past or current severe bleeding (bleeding >30 ml within 3 months), hemoptysis (>5 ml fresh blood within 4 weeks), or thromboembolic events (including stroke events and/or transient cerebral deficiencies) within 12 months Blood attack);
11) Subjects are still using Chinese medicine immunomodulators within 2 weeks before enrollment;
12) Subjects have active infections or have unexplained fever> 38.5 degrees during the screening period and before the first administration (according to the judgment of the investigator, the subject can be included in the group due to fever caused by the tumor);
13) Past and current patients with objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lung function, etc.;
14) Subjects with congenital or acquired immune deficiencies, such as HIV infection, or active hepatitis (transaminase does not meet the selection criteria, hepatitis B reference: HBV DNA≥10?/ml; hepatitis C reference: HCV RNA≥103/ml); chronic Carriers of hepatitis B virus, HBV DNA <2000 IU/ml (<104 copies/ml), must receive antiviral therapy at the same time during the trial period before they can be included in the group;
15) The subject is participating in other clinical studies or is less than one month away from the end of the previous clinical study; the subject may receive other systemic anti-tumor treatments during the study period;
16) Live vaccine may be vaccinated less than 4 weeks before study medication or may be inoculated during the study period;
17) The subject has a known history of psychotropic drug abuse, alcohol abuse or drug abuse;
18) The subject has received traditional Chinese medicine treatment within 4 weeks before the first treatment;
19) Subjects cannot or do not agree to bear the self-funded part of the inspection and treatment costs, except for clinical research drugs, combined chemotherapy and SAEs related to clinical research drugs combined with chemotherapy;
20) The investigator believes that it should be excluded from this study. For example, according to the investigators judgment, the subject has other factors that may cause the study to be terminated halfway, such as other serious diseases (including mental illness) that require combined treatment. Serious laboratory examination abnormalities, accompanied by family or social factors, will affect the safety of subjects or the collection of data and samples.m

研究实施时间：

Study execute time：

从 From 2021-06-02 00:00:00至 To 2025-07-08 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2021-07-20 00:00:00 至 To 2022-07-01 00:00:00  

干预措施：

Interventions：

组别：

实验组

样本量：

48

Group：

test group

Sample size：

干预措施：

卡瑞利珠单抗

干预措施代码：

Intervention：

Camrelizumab

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 天津 

市(区县)：

  

Country：

China 

Province：

Tianjin 

City：

 

单位(医院)：

天津医科大学总医院 

单位级别：

三级甲等 

Institution
hospital：

Tianjin Medical University General Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

3年无进展生存（PFS）率

指标类型：

主要指标

Outcome：

3-year progression-free survival (PFS) 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：

病理完全缓解率

指标类型：

次要指标

Outcome：

Pathological complete remission rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无复发生存期

指标类型：

次要指标

Outcome：

Recurrence-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：

术后并发症发生率

指标类型：

次要指标

Outcome：

Postoperative complication rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

手术切除率

指标类型：

次要指标

Outcome：

Surgical resection rate

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

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：

无

组织：

Sample Name：

N/A

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

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 岁 years
最大 Max age 岁 years

性别：

男性

Gender：

Male

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)：

无

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）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

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）：

2026年12月

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

December 2026

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：

EDC

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

EDC

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2021-07-19 15:24:51