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：	ChiCTR2000036613
最近更新日期： Date of Last Refreshed on：	2021-09-21 02:12:54
注册时间： Date of Registration：	2020-08-24 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	苏杭医师：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微波消融联合免疫检查点抑制剂治疗同期多发肺癌的疗效和安全性研究：一项开放、多中心的II期临床试验
Public title：	Efficacy and safety of microwave ablation combined with immunocheckpoint inhibitor for concurrent multiple lung cancers: an open, multicenter phase II clinical trial
注册题目简写：
English Acronym：
研究课题的正式科学名称：	微波消融联合免疫检查点抑制剂治疗同期多发肺癌的疗效和安全性研究：一项开放、多中心的II期临床试验
Scientific title：	Efficacy and safety of microwave ablation combined with immunocheckpoint inhibitor for concurrent multiple lung cancers: an open, multicenter phase II clinical trial
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：	苏杭	研究负责人：	陈昶
Applicant：	Su Hang	Study leader：	Chen Chang
申请注册联系人电话： Applicant telephone：	+86 16628768769	研究负责人电话： Study leader's telephone：	+86 16628768769
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：	dreamsuhang@163.com	研究负责人电子邮件： Study leader's E-mail：	chenthoracic@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：	上海市杨浦区政民路507号	研究负责人通讯地址：	上海市杨浦区政民路507号
Applicant address：	507 Zhengmin Road, Yangpu District, Shanghai, China	Study leader's address：	507 Zhengmin Road, Yangpu District, Shanghai, China
申请注册联系人邮政编码： Applicant postcode：	200433	研究负责人邮政编码： Study leader's postcode：	200433
申请人所在单位：	上海市肺科医院
Applicant's institution：	Shanghai Pulmonary Hospital
研究负责人所在单位：	上海市肺科医院
Affiliation of the Leader：	Shanghai Pulmonary Hospital

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：

上海市肺科医院

Primary sponsor：

Shanghai Pulmonary Hospital

研究实施负责（组长）单位地址：

上海市杨浦区政民路507号

Primary sponsor's address：

507 Zhengmin Road, Yangpu District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海市肺科医院	具体地址：	杨浦区政民路507号
Institution hospital：	Shanghai Pulmonary Hospital	Address：	507 Zhengmin Road, Yangpu District

经费或物资来源：

上海申康医院发展中心

Source(s) of funding：

Shanghai Hospital Development Center

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：

其它

Study phase：

N/A

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

探究微波消融联合免疫检查点抑制剂治疗驱动基因阴性的多原发肺癌患者，观察术后生存情况，评价可操作性、安全性等。

Objectives of Study：

To explore the negative-diver gene multiple primary lung cancer patients treated with microwave ablation combined with immune checkpoint inhibitors, observe postoperative survival, and evaluate operability and safety, etc.

药物成份或治疗方案详述：

1) 经CT确诊的多发肺部结节，靶病灶个数≥2个且≤5个（靶病灶：单个结节最大径≥8 mm或实性成分最大径≥5mm，且单个结节最大径≤30 mm），靶病灶至少分布于两个肺叶，然后由临床医师根据纳入标准和排除标准初步决定该患者是否符合进入本实验的条件； 2) 对于符合条件者，由参与本项目的医师共同向患者介绍本实验的相关情况，并由患者自行选择是否参加本实验，根据患者意愿及术者评估，决定行电磁导航支气管镜引导肺内微波消融术或经皮微波消融术； 3) 同意参加本试验者，须事先签订一份“临床试验知情同意书”。符合研究条件的受试者，入组后接受微波消融治疗。 1) 依据病灶位置、主刀医生经验专长选择经皮消融路径/经支气管消融路径。若患者多个靶病灶需共同使用经皮和经气管路径，应考虑先行经支气管路径消融；若需行经皮双侧消融术，应考虑两侧病灶分期手术；消融术中取肿瘤组织做病理检查及基因检测。 2) 微波消融治疗效果评估：术后CT扫描显示消融区完全重叠或包围靶病灶，包括消融切缘的区域时，该手术被定义为技术成功； 3) 免疫检查点抑制剂联合治疗：术后病理确认多原发肺癌且至少一个靶病灶基因检测EGFR、ALK、ROS1融合、BRAF V600E突变、NTRK融合均阴性（否则出组）。 4）微波消融后2周内接受卡瑞利珠单抗治疗，静脉滴注给药，固定剂量 200 mg，以30分钟时间静脉滴注（包括冲管时间在内整体滴注时间不短于20分钟，不长于60分钟），每3周1次。从第1次给药开始，直至出现疾病进展/恶化或经影像学确认的疾病进展/或不可耐受毒副反应发生，卡瑞利珠单抗累计用药不超过16个周期。

Description for medicine or protocol of treatment in detail：

1) Multiple pulmonary nodules diagnosed by CT, the number of target lesions >= 2 and <= 5 (target lesions: the largest diameter of a single nodule >= 8 mm or the largest diameter of a solid component >= 5mm, and the largest diameter of a single nodule <= 30 mm), the target lesions are distributed in at least two lung lobes, and then the clinician will preliminarily determine whether the patient meets the conditions for entering this experiment according to the inclusion and exclusion criteria; 2) For those eligible, the physicians participating in this project will jointly introduce the relevant conditions of the experiment to the patient, and the patient will choose whether to participate in the experiment. According to the patient's wishes and the evaluation of the surgeon, it is decided to conduct electromagnetic navigation bronchoscopy to guide the lungs Microwave ablation or percutaneous microwave ablation; 3) Those who agree to participate in this trial must sign a "Clinical Trial Informed Consent" in advance. Subjects who meet the research conditions will receive microwave ablation therapy after enrollment. 1) Choose the percutaneous ablation path/transbronchial ablation path based on the location of the lesion and the experience and expertise of the surgeon. If multiple target lesions in patients need to use percutaneous and transtracheal pathways together, transbronchial ablation should be considered first; if percutaneous bilateral ablation is required, staged surgery on both sides of the lesion should be considered; tumor tissues should be taken for pathological examination during ablation And genetic testing. 2) Evaluation of the effect of microwave ablation treatment: When the postoperative CT scan shows that the ablation area completely overlaps or surrounds the target lesion, including the area of ??the ablation margin, the operation is defined as a technical success; 3) Combination therapy with immune checkpoint inhibitors: postoperative pathological confirmation of multiple primary lung cancers and at least one target lesion gene detection of EGFR, ALK, ROS1 fusion, BRAF V600E mutation, and NTRK fusion are all negative (otherwise out of the group). 4) Receive carrelizumab treatment within 2 weeks after microwave ablation, intravenous drip administration, fixed dose 200 mg, intravenous drip in 30 minutes (including flushing time, the overall infusion time is not less than 20 Minutes, not longer than 60 minutes), once every 3 weeks. From the first administration, until disease progression/worsening or imaging confirmed disease progression/or intolerable toxic side effects occur, the cumulative use of carrelizumab does not exceed 16 cycles.

纳入标准：

Inclusion criteria

1) Aged 18-79 years;
2) Multiple pulmonary nodules diagnosed by CT, the number of target lesions is >= 2 and <= 5 (definition of target lesions: the largest diameter of a single nodule is >= 8 mm or the largest diameter of a solid component is >= 5mm, and a single nodule is the largest Diameter <= 30 mm), the target lesions are distributed in at least two lung lobes;
3) The target lesions need to be pathologically indicated as lung cancer, and at least one of the target lesions is pathologically diagnosed as lung cancer (at least one target lesion is pathologically diagnosed as lung cancer, and the CT follow-up after anti-inflammatory treatment for the remaining target lesions is clear and stable for no less than 3 months, which is also consistent with the entry Group conditions);
4) The patient has no lymph node metastasis, lung metastasis or distant organ metastasis (N0, M0);
5) ECOG PS score 0-2;
6) Expected survival time >= 12 months;
7) Sufficient hematology function, defined as absolute neutrophil count >= 1.5 x 10^9/L, platelet count >= 80 x 10^9/L, hemoglobin >= 90g/L (no history of blood transfusion within 7 days, no G-CSF and others Correction of hematopoietic stimulating factors);
8) Sufficient liver function, defined as all patients with total bilirubin level <= 1.5 times upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels <= 2.5 times ULN;
9) Sufficient renal function, defined as creatinine clearance >= 50ml/min (Cockcroft-Gault formula);
10) The coagulation function is adequate, defined as the international normalized ratio (INR) or prothrombin time (PT) <= 1.5 times ULN; if the subject is receiving anticoagulation therapy, as long as the INR/PT is within the proposed range of anticoagulation drugs Can;
11) For female subjects of childbearing age, the urine or serum pregnancy test should be negative within 3 days before receiving the first study drug administration. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required;
12) If there is a risk of conception, male and female patients need to use high-efficiency contraception (that is, a method with a failure rate of less than 1% per year) and continue until at least 180 days after stopping the trial treatment;
13) Subjects voluntarily join the study and sign written informed consent before any trial-related procedures are implemented. They have good compliance and cooperate with follow-up.

排除标准：

1) 基因检测患者病灶EGFR、ALK、ROS1融合、BRAF V600E 突变、NTRK 融合至少一个突变阳性；
2) 术前影像学检查肺部结节最大径>30mm 者；
3) 术前影像学检查或者纵隔淋巴结穿刺提示术前淋巴结阳性患者；
4) 术前检查发现有远处转移或有胸、腹水者；
5) 当前正在参与干预性临床研究治疗，或在首次干预前3月内接受过其他研究药物或研究器械治疗；
6) 肿瘤消融术前进行过任何系统性抗肿瘤治疗，包括介入化疗栓塞、放疗、化疗、靶向治疗或具有抗肿瘤适应症的中成药或免疫调节作用的药物（胸腺肽、干扰素、白介素等），或首次干预前 3 周内接受过重大手术治疗；
7) 既往接受过下列疗法：抗PD-1、抗PD-L1或抗PD-L2药物或者针对另一种刺激或协同抑制T细胞受体（例如，CTLA4、OX-40、CD137）的药物；
8) 具有影响手术或消融术的多种因素（比如凝血功能障碍、免疫系统疾病等）；
9) 凝血功能异常（PT>16 s、APTT>43 s、TT>21 s、Fbg< 2 g/L），具有出血倾向（如活动性消化道溃疡）或正在接受溶栓或抗凝治疗；
10) 首次干预前4周内出现≥CTCAE 2级的肺出血；就诊前4周内出现≥CTCAE 3级的其它部位出血；
11) 已知有人类免疫缺陷病毒（HIV）感染史（即HIV 1/2 抗体阳性），已知的梅毒感染（梅毒抗体阳性），活动性肺结核，未经治疗的活动性肝炎；
12) 心、肝、肾功能严重损害者（心功能3～4级，ALT和/或AST超过正常上限3倍以上，Cr超过正常上限）；
13) 已知存在可能对遵从试验要求产生影响的精神疾病或药物滥用情况；
14) 合并其他恶性肿瘤或血液病患者；
15) 妊娠、计划妊娠及哺乳期女性患者（尿HCG>2500IU/L 时，诊断为早期妊娠）；
16) 研究者认为不适合纳入者。

Exclusion criteria：

1) Genetic testing is positive for at least one mutation of EGFR, ALK, ROS1 fusion, BRAF V600E mutation, and NTRK fusion;
2) Pulmonary nodules with the largest diameter > 30mm in preoperative imaging examination;
3) Preoperative imaging examination or mediastinal lymph node puncture indicates patients with positive preoperative lymph nodes;
4) Patients with distant metastasis or chest or ascites found in preoperative examination;
5) Currently participating in interventional clinical research treatment, or receiving treatment with other research drugs or research devices within 3 months before the first intervention;
6) Any systemic anti-tumor treatment before tumor ablation, including interventional chemoembolization, radiotherapy, chemotherapy, targeted therapy, or Chinese patent medicine with anti-tumor indications or immunomodulatory drugs (thymosin, interferon, interleukin, etc.) ), or received major surgery within 3 weeks before the first intervention;
7) Have received the following therapies in the past: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs that stimulate or synergistically inhibit T cell receptors (for example, CTLA4, OX-40, CD137);
8) There are multiple factors that affect surgery or ablation (such as coagulation dysfunction, immune system disease, etc.);
9) Abnormal coagulation function (PT > 16 s, APTT > 43 s, TT > 21 s, Fbg < 2 g/L), bleeding tendency (such as active peptic ulcer) or receiving thrombolytic or anticoagulant therapy;
10) Pulmonary hemorrhage >= CTCAE grade 2 occurred within 4 weeks before the first intervention; other parts of hemorrhage >= CTCAE grade 3 occurred within 4 weeks before treatment;
11) Known history of human immunodeficiency virus (HIV) infection (ie HIV 1/2 antibody positive), known syphilis infection (syphilis antibody positive), active tuberculosis, active hepatitis without treatment;
12) People with severe impairment of heart, liver, and kidney functions (heart function grades 3 to 4, ALT and/or AST are more than 3 times the upper limit of normal, and Cr exceeds the upper limit of normal);
13) Known mental illness or drug abuse that may affect compliance with test requirements;
14) Patients with other malignant tumors or hematological diseases;
15) Pregnant, planned pregnancy and breast-feeding women (when urine HCG>2500IU/L, the diagnosis is early pregnancy
pregnant);
16) The investigator believes that it is not suitable for inclusion.

研究实施时间：

Study execute time：

从 From 2021-04-15 00:00:00至 To 2022-09-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2021-04-15 00:00:00 至 To 2022-09-30 00:00:00

干预措施：

Interventions：

组别：	微波消融术后免疫治疗组	样本量：	73
Group：	Immunotherapy group after microwave ablation	Sample size：	73
干预措施：	微波消融术+PD-1单抗治疗	干预措施代码：
Intervention：	Microwave ablation + PD-1 monoclonal antibody treatment	Intervention code：

组别：	微波消融组	样本量：	73
Group：	Microwave ablation	Sample size：	73
干预措施：	微波消融治疗	干预措施代码：
Intervention：	Microwave ablation	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	shanghai	City：
单位(医院)：	上海市肺科医院	单位级别：	三级甲等
Institution hospital：	Shanghai Pulmonary Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海交通大学医学院附属瑞金医院	单位级别：	三级甲等
Institution hospital：	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	中国人民解放军海军军医大学第一附属医院	单位级别：	三级甲等
Institution hospital：	Changhai Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海市第一人民医院	单位级别：	三级甲等
Institution hospital：	Shanghai First People's Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海市第十人民医院	单位级别：	三级甲等
Institution hospital：	Shanghai Tenth People's Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海交通大学医学院附属仁济医院	单位级别：	三级甲等
Institution hospital：	Renji Hospital, Shanghai Jiaotong University School of Medicine	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	2年、3年、5年无复发生存率	指标类型：	主要指标
Outcome：	Disease free survival at the 2ed, 3rd and 5th year	Type：	Primary indicator
测量时间点：	2年、3年、5年	测量方法：	定期随访
Measure time point of outcome：	The 2nd, 3rd and 5th year after treatment	Measure method：	Regular follow-up after treatment

指标中文名：	3年、5年总生存率	指标类型：	次要指标
Outcome：	Overall survival at the 3rd and 5th year	Type：	Secondary indicator
测量时间点：	3年、5年	测量方法：	定期随访
Measure time point of outcome：	The 3rd and 5th year after treatment	Measure method：	Regular follow-up

指标中文名：	术后生活质量评分	指标类型：	次要指标
Outcome：	Postoperative quality of life score	Type：	Secondary indicator
测量时间点：	术后	测量方法：	EORTC QLQ-C30评分表
Measure time point of outcome：	Postoperation	Measure method：	EORTC QLQ-C30

指标中文名：	并发症发生率	指标类型：	次要指标
Outcome：	Incidence of complications	Type：	Secondary indicator
测量时间点：	术后围术期及用药时期	测量方法：	术后随访
Measure time point of outcome：	Perioperative period after operation and during treatment	Measure method：	Follow-up after operation

指标中文名：	临床显著性毒性发生率	指标类型：	主要指标
Outcome：	Incidence of clinically significant toxicity	Type：	Primary indicator
测量时间点：	开始用卡瑞利珠单抗2周期后	测量方法：	随访+检查
Measure time point of outcome：	After 2 cycles of Carrelizumab started	Measure method：	Follow-up + inspection

指标中文名：	非靶病灶无进展率	指标类型：	次要指标
Outcome：	Non-target lesion progression-free rate	Type：	Secondary indicator
测量时间点：	治疗后	测量方法：	随访+检查
Measure time point of outcome：	After treatment	Measure method：	Follow-up and inspection

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	肺组织	组织：	肺脏
Sample Name：	The lung tissue	Tissue：	The lung
人体标本去向	使用后保存	说明	标本大部分销毁，穿刺肺结节按要求进行冰冻病理检查
Fate of sample：	Preservation after use	Note：	Most of the specimens were destroyed, and pulmonary tuberous puncture specimens were subjected to frozen pathological examination

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	79	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）：

患者符合全部入组条件后按顺序拆取随机信封

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

After the patients meet all the enrollment conditions, the random envelopes will be removed in order

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：	开放试验
Blinding：	Open trial
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）：	随发表论文公开共享请阅读网页注册指南中关于原始数据共享的内容。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The original data will be shared along with the publication of our results.
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：	病例记录表和医院医疗电子信息采集管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Case Report Form (CRF) and the Electronic Data Capture in Hospital
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2020-08-24 11:07:42