ChiCTR2100050097 版本V1.3 版本创建时间2022/03/16 19:43:43 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：

 ChiCTR2100050097 

最近更新日期：

Date of Last Refreshed on：

 2022-03-16 19:40:44 

注册时间：

Date of Registration：

 2021-08-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

请于伦理委员会批准后才开始征募参试者，并与我们联系上传伦理批件。 化疗联合PD-1抑制剂序贯放疗联合PD-1抑制剂治疗晚期非小细胞肺癌的前瞻性、多中心、单臂临床研究

Public title：

A prospective, multicenter, single-arm clinical study of chemotherapy combined with PD-1 inhibitor sequential radiotherapy combined with PD-1 inhibitor in the treatment of 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：

化疗联合PD-1抑制剂序贯放疗联合PD-1抑制剂治疗晚期非小细胞肺癌

Scientific title：

A prospective, multicenter, single-arm clinical study of chemotherapy combined with PD-1 inhibitor sequential radiotherapy combined with PD-1 inhibitor in the treatment of 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：

叶华 

研究负责人：

林盛 

Applicant：

Ye Hua 

Study leader：

Lin Sheng 

申请注册联系人电话：

Applicant telephone：

 +86 13568637417

研究负责人电话：

Study leader's
telephone：

+86 15108187773

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：

 307524082@QQ.com

研究负责人电子邮件：

Study leader's E-mail：

 lslinsheng@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：

四川省泸州市江阳区太平街25号

研究负责人通讯地址：

四川省泸州市江阳区太平街25号

Applicant address：

25 Taiping Street, Jiangyang District, Luzhou, Sichuan

Study leader's address：

25 Taiping Street, Jiangyang District, Luzhou, Sichuan

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：

西南医科大学附属医院肿瘤科

Applicant's institution：

Affiliated Hospital of Southwest Medical University

研究负责人所在单位：

Affiliation of the Leader：

是否获伦理委员会批准：

否

Approved by ethic committee：

No

伦理委员会批件文号：

Approved No. of ethic committee：

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：

Name of the ethic committee：

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：

Contact Name of the ethic committee：

伦理委员会联系地址：

Contact Address of the ethic committee：

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：

西南医科大学附属医院肿瘤科

Primary sponsor：

Affiliated Hospital of Southwest Medical University

研究实施负责（组长）单位地址：

四川省泸州市江阳区太平街25号

Primary sponsor's address：

25 Taiping Street, Jiangyang District, Luzhou, Sichuan

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)：

泸州

Country：

China

Province：

Sichuan

City：

Luzhou

单位(医院)：

西南医科大学附属医院肿瘤科

具体地址：

江阳区太平街25号

Institution
hospital：

Affiliated Hospital of Southwest Medical University

Address：

25 Taiping Street, Jiangyang District

经费或物资来源：

科研基金

Source(s) of funding：

scientific-research funding

研究疾病：

晚期非小细胞肺癌  

Target disease：

advanced non-small cell 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：

 II期临床试验 

Study phase：

2

研究设计：

横断面 

Study design：

Cross-sectional 

研究目的：

评估化疗联合PD-1抑制剂序贯放疗联合PD-1抑制剂治疗晚期非小细胞肺癌的有效性和安全性。  

Objectives of Study：

To evaluate the efficacy and safety of chemotherapy combined with PD-1 inhibitor sequential radiotherapy combined with PD-1 inhibitor in the treatment of advanced non-small cell lung cancer.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1. 组织学或细胞学证实，胸部增强CT、肝脏及肾上腺CT、头颅磁共振、PET-CT/全身骨显像等明确分期的不可手术切除或无法进行根治性放化疗的ⅢB-ⅣB期驱动基因阴性的NSCLC患者；由多学科团队（至少包含有一名胸外科医师）来评估；
2. 患者年龄年龄18～75岁，能够表示知情同意并签订知情同意书，能够依从研究方案和随访流程；
3. 患者必须有 ≥ 3处可测量病灶（按照RECIST 1.0标准）； 无放疗禁忌症，预期寿命大于6个月；
4. 美国东部肿瘤合作组(Eastern Cooperative Group, ECOG) 评分量表评估0-2分；
5. 有足够的肺功能，要求：第1秒钟用力呼吸容积（FEV1）≥1.2升/秒或≥50%预计值,术后预期（FEV1）≥30％ ；
6. 既往无其他肺部恶性肿瘤史，未行针对肺部肿瘤的化疗或放疗；
7. 距前次接受放疗、化疗、激素治疗和分子靶向治疗4 周以上，先前治疗引起的所有不良事件已恢复到≤Ⅰ度 (CTCAE 4.0)的患者；
8. 在首次用药前7天内进行的下列实验室检查，证实患者骨髓、肝肾功能符合参加研究的要求：血红蛋白≥9.0 g/dL（可以通过输血维持或超过这个水平）；红细胞计数≥2.0×10^9/L 中性粒细胞绝对计数（ANC）≥1.0×10^9/L；血小板计数≥100×10^9/L；总胆红素在正常限值内；谷丙转氨酶、谷草转氨酶、碱性磷酸酶≤2.5倍正常值上限；肌酐≤2.0 mg/dL；且肌酐清除率≥60ml/min； 未曾接受抗凝治疗的患者凝血酶原时间国际标准化比值（INR）≤1.5，部分凝血活酶时间(APTT)≤1.5倍正常值上限。接受全量或胃肠外抗凝药物治疗的患者只要在进入临床研究前抗凝药物的剂量稳定至少2周，并且凝血检测试验的结果在当地治疗所限制的范围以内均可以进入临床试验; -其余筛查所做的实验室检查值必须符合相关标准；
9.育龄期妇女在治疗开始前7天内检测尿及血清HCG，结果需阴性；适龄期男女患者在进入试验前，研究过程中直到停药后30天都必须采用可靠的方法避孕。可靠的避孕方法将由主要研究者或指定人员来判定。

Inclusion criteria

1. Histologically or cytologically confirmed, patients with stage IIIB-IVB driver gene-negative NSCLC who are unresectable or unable to undergo radical chemoradiotherapy and have definite stages such as chest enhanced CT, liver and adrenal CT, head magnetic resonance, PET-CT/whole body bone imaging, etc.; assessment by a team (including at least one thoracic surgeon);
2. Aged 18 to 75 years, able to express informed consent and sign an informed consent form, and be able to comply with the research protocol and follow-up procedures;
3. Patients must have >= 3 measurable lesions (according to RECIST 1.0 criteria); no contraindications to radiotherapy, and life expectancy is greater than 6 months;
4. The Eastern Cooperative Group (ECOG) scoring scale evaluates 0-2 points;
5. Sufficient lung function, requirements: forced expiratory volume in the first second (FEV1) >= 1.2 liters/second or >= 50% of the expected value, postoperative expected (FEV1) >= 30%;
6. No history of other lung cancers, no chemotherapy or radiotherapy for lung tumors;
7. Patients who received radiotherapy, chemotherapy, hormone therapy and molecular targeted therapy for more than 4 weeks, and all adverse events caused by previous therapy have recovered to <= grade I (CTCAE 4.0);
8. The following laboratory tests performed within 7 days before the first drug use confirmed that the patient's bone marrow, liver and kidney functions meet the requirements for participation in the study: hemoglobin >= 9.0 g/dL (which can be maintained or exceeded by blood transfusion); red blood cell count >=2.0x10^9/L, absolute neutrophil count (ANC) >=1.0x10^9/L; platelet count >=100x10^9/L; total bilirubin within the normal limit; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase <= 2.5 times the upper limit of normal; creatinine <= 2.0 mg/dL; and creatinine clearance rate >= 60ml/min; in patients who had not received anticoagulation therapy, the international normalized ratio (INR) of prothrombin time was <=1.5, and the partial thromboplastin time (APTT) was <=1.5 times the upper limit of normal. Patients receiving full-dose or parenteral anticoagulant therapy can enter clinical trials as long as the dose of anticoagulant drugs is stable for at least 2 weeks before entering the clinical study, and the results of the coagulation test are within the limits of local treatment; laboratory test values for the remaining screenings must meet relevant standards;
9. Women of childbearing age should test urine and serum HCG within 7 days before the start of treatment, and the results must be negative; patients of appropriate age must use a reliable method of contraception before entering the trial and during the study until 30 days after stopping the drug. Reliable contraceptive methods will be adjudicated by the principal investigator or designee.

排除标准：

1.任何不稳定的系统性疾病（包括活动性感染、未得到控制的高血压、不稳定型心绞痛、最近3个月内开始发作的心绞痛、充血性心功能衰竭（≥纽约心脏病协会【NYHA】 II级）、心机梗塞（入组前6个月）、需要药物治疗的严重心律失常、肝脏，肾脏或代谢性疾病；
2.合并有不受控制神经病变（2级或以上）或精神病患者；
3.有活动性、已知或怀疑有自身免疫性疾病。有下列病症的受试者可以入选：白癜风，I型糖尿病，只需要用激素替代治疗的、自身免疫性甲状腺炎所致的残留性甲状腺功能减退，或预计没有外界因素刺激不会复发的病症；
4.以前用过抗PD-1抗体、抗PD-L1抗体、抗PD-L2抗体或抗CTLA-4抗体治疗（或作用于T细胞协同刺激或检查点通路的任何其他抗体）；
5.根据胸部X线检查、痰液检查以及临床查体，判断有活动性肺结核（TB）感染。前1年内有活动性肺结核感染病史的患者，即使已经治疗，也要排除。超过1年以前有活动性肺结核感染病史的患者，也要排除，除非能够证明以前所用的抗结核治疗充分有效；
6.已知有人免疫缺陷病毒（HIV）检查阳性病史或已知有获得性免疫缺陷综合征（艾滋病）；
7.需要用免疫抑制药物治疗的合并症，或需要按具有免疫抑制作用的剂量全身或局部使用皮质类固醇的合并症；
8.既往相同部位接受过放疗导致不能接受本次大分割放疗；
9.哺乳期妇女；
10.在首次用药前2个月内进行过大手术或受严重外伤的患者；
11.对研究药物过敏；
12.其他研究者认为不适合入组的情况。

Exclusion criteria：

1. Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina pectoris, angina pectoris that started within the last 3 months, congestive heart failure (>= New York Heart Association [NYHA] class II), myocardial infarction (6 months prior to enrollment), severe arrhythmia requiring drug therapy, liver, kidney or metabolic disease;
2. Patients with uncontrolled neuropathy (grade 2 or above) or mental illness;
3. Active, known or suspected autoimmune disease. Subjects with the following conditions can be included: vitiligo, type I diabetes, residual hypothyroidism caused by autoimmune thyroiditis only with hormone replacement therapy, or conditions that are not expected to recur without external stimulation;
4. Previous treatment with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell costimulation or checkpoint pathway);
5. According to chest X-ray examination, sputum examination and clinical physical examination, it is judged that there is active pulmonary tuberculosis (TB) infection. Patients with a history of active pulmonary tuberculosis infection within the previous 1 year were excluded even if they had been treated. Patients with a history of active pulmonary tuberculosis infection more than 1 year ago should also be excluded unless it can be demonstrated that the previous anti-tuberculosis treatment was sufficiently effective;
6. Known positive medical history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
7. Complications requiring treatment with immunosuppressive drugs, or comorbidities requiring systemic or topical corticosteroids at doses with immunosuppressive effects;
8. Patients who have received radiotherapy at the same site in the past cannot receive this hypofractionated radiotherapy;
9. Breastfeeding patients;
10. Patients who have undergone major surgery or suffered severe trauma within 2 months before the first drug;
11. Allergic to the research drug;
12. Other researchers think that it is not suitable for enrollment.

研究实施时间：

Study execute time：

从 From 2021-09-01 00:00:00至 To 2022-08-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2021-09-01 00:00:00 至 To 2024-08-31 00:00:00

干预措施：

Interventions：

组别：

干预组

样本量：

 436

Group：

Intervention group

Sample size：

干预措施：

化疗联合PD-1抑制剂序贯放疗联合PD-1抑制剂

干预措施代码：

Intervention：

Chemotherapy Combined with Pd-1 Inhibitor Sequential Radiotherapy Combined with Pd-1 Inhibitor

Intervention code：

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)：

 泸州 

Country：

China

Province：

Sichuan

City：

Luzhou

单位(医院)：

 西南医科大学附属医院 

单位级别：

 三级甲等 

Institution
hospital：

Affiliated Hospital of Southwest Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

总生存

指标类型：

主要指标

Outcome：

Overall survival, OS

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存

指标类型：

次要指标

Outcome：

Progression-free survival, PFS

Type：

Secondary 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 remission rate,ORR

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性和耐受性

指标类型：

次要指标

Outcome：

Safety and tolerability

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

健康相关的生活质量

指标类型：

次要指标

Outcome：

Health-related quality of life

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：

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 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）：

单臂研究，无随机分组

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

It is a single-arm study without randomized grouping.

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

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）：

原始数据公开为2027年3月1日，采用excel表格或者病例记录表共享

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

Raw data was publicly available in March 1, 2027 and was shared by Excel forms or case records

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：

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，并每周上传至研究者指定邮箱

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

Data collection and management consists of two parts. One is Case Record (CRF), the other is electronic collection, and the data is assigned to the researcher’s email every week

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2021-08-16 12:42:19