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：	ChiCTR2400091364
最近更新日期： Date of Last Refreshed on：	2025-02-20 08:44:29
注册时间： Date of Registration：	2024-10-28 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项替雷利珠单抗联合化疗二线治疗免疫经治EGFR/ALK/ROS1阴性晚期NSCLC患者的探索性研究
Public title：	An exploratory study of tislelizumab in combination with chemotherapy in immuno-experienced patients with EGFR/ALK/ROS1-negative advanced NSCLC in the second-line setting
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项替雷利珠单抗联合化疗二线治疗免疫经治EGFR/ALK/ROS1阴性晚期NSCLC患者的探索性研究
Scientific title：	An exploratory study of tislelizumab in combination with chemotherapy in immuno-experienced patients with EGFR/ALK/ROS1-negative advanced NSCLC in the second-line setting
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：	苏春霞	研究负责人：	苏春霞
Applicant：	Chunxia Su	Study leader：	Chunxia Su
申请注册联系人电话： Applicant telephone：	+86 21 65115006 3062	研究负责人电话： Study leader's telephone：	+86 21 65115006 3062
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：	susu_mail@126.com	研究负责人电子邮件： Study leader's E-mail：	susu_mail@126.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：	zhengming Road 507	Study leader's address：	zhengming Road 507
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：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	L24-526-1	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：	上海市肺科医院医学伦理委员会
Name of the ethic committee：	Shanghai Pulmonary Hospital Medical Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2024-10-09 00:00:00
伦理委员会联系人：	桂涛
Contact Name of the ethic committee：	GUI TAO
伦理委员会联系地址：	上海市杨浦区政民路507号
Contact Address of the ethic committee：	No. 507, Zhengmin Road, Yangpu District, Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 6511 5006	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：

No.507, Zhengmin Road, 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)：	杨浦区
Country：	China	Province：	Shanghai	City：	yangpu district
单位(医院)：	上海市肺科医院	具体地址：	上海市杨浦区政民路507号
Institution hospital：	Shanghai pulmonary hospital	Address：	No. 507, Zhengmin Road, Yangpu District, Shanghai

经费或物资来源：

上海市肺科医院

Source(s) of funding：

Shanghai pulmonary hospital

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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

初步探索地舒单抗联合替雷利珠单抗及化疗二线治疗免疫经治EGFR/ALK/ROS1阴性晚期NSCLC患者的疗效及安全性

Objectives of Study：

To explore the efficacy and safety of denosumab in combination with tislelizumab and chemotherapy in the second-line treatment of immuno-experienced patients with EGFR/ALK/ROS1-negative advanced NSCLC

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; 
(2) Patients with histologically or cytologically confirmed non-bone metastases stage IV NSCLC;
(3) EGFR, ALK, and ROS1 are all wild-type (for other driver genes, if there is no first-line approval for corresponding targeted therapy or if the patient refuses targeted therapy, these patients are allowed to be enrolled);
(4) first-line treatment with immune checkpoint inhibitors and clinical benefit (PFS ≥ 3 months);
(5) Have measurable lesions (according to RECIST 1.1 criteria, the long diameter of CT scan of tumor lesions is ≥10mm, the short diameter of CT scan of lymph node lesions is ≥15mm, and the thickness of the scanning layer is not more than 5mm, and the measurable lesions have not received local treatment such as radiotherapy and cryotherapy);
(6) ECOG PS: 0-2 points;
(7) Estimated survival time≥ 3 months;
(8) Adequate hematologic function, defined as absolute neutrophil count ≥1.5×109/L, platelet count ≥ 80×109/L, hemoglobin ≥ 90g/L (no history of blood transfusion within 7 days, not corrected with G-CSF and other hematopoietic stimulating factors); 
(9) adequate liver function, defined as total bilirubin levels ≤1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN, or for patients with liver metastases, AST and ALT levels ≤ 5 times ULN;
(10) adequate renal function, defined as creatinine clearance ≥50ml/min (Cockcroft-Gault formula);
(11) Adequate coagulation function, defined as the international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;
(12) For female subjects of childbearing age, a negative urine or serum pregnancy test should be performed within 3 days prior to receiving the first dose of study drug, and if the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required;
(13) If there is a risk of conception, male and female patients need to use highly effective contraception (i.e., a method with a failure rate of less than 1% per year) and continue until at least 180 days after stopping the trial treatment (Note: abstinence can be accepted as a contraceptive method if abstinence is the subject's usual lifestyle and preferred contraceptive method);
(14) Subjects voluntarily joined this study, signed a written informed consent form before the implementation of any trial-related procedures, had good compliance, and cooperated with follow-up.

排除标准：

（1）一线使用多西他赛化疗的患者；（2）有症状脑转移患者（脑转移病灶经过治疗后症状保持临床稳定状态至少1个月，且进入研究前至少1个月不使用类固醇和抗惊厥药物可以入组）；（3）存在临床上不可控制的胸腔积液/腹腔积液（不需要引流积液或停止引流 3 天积液无明显增加的患者可以入组）；（4）在开始治疗前，尚未从任何干预措施引起的毒性和/或并发症中充分恢复（即≤1级或达到基线，不包括乏力或脱发）；（5）在首次给药前5年内诊断为其他恶性肿瘤，不包括经过根治的皮肤基底细胞癌、皮肤鳞状细胞癌和/或经过根治切除的原位癌，如果给药前5年以上诊断为其他恶性肿瘤或肺癌，需对复发转移病灶进行病理学或细胞学诊断；（6）存在需临床干预的活动性咯血、活动性憩室炎、腹腔脓肿、胃肠道梗阻和腹膜转移；（7）接受过实体脏器或血液系统移植；（8）III-IV级充血性心力衰竭（纽约心脏病协会分级），控制不佳且有临床意义的心律失常；（9）首次给药前2年内发生过需要全身性治疗（例如使用病情改善药物、皮质类固醇或免疫抑制剂）的活动性自身性免疫疾病。替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理剂量皮质类固醇等）不视为全身性治疗；（10）需要长期全身性使用皮质类固醇的患者（由于COPD、哮喘需要间断使用支气管扩张药、吸入性皮质类固醇，或局部注射皮质类固醇的患者可以入组）；（11）首次给药前1年内存在需要皮质类固醇治疗的非感染性肺炎病史；（12）有需要治疗的活动性感染或首次给药前一周内使用过全身性抗感染药物；（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）研究者认为不适合纳入者。

Exclusion criteria：

(1) Patients on first-line docetaxel chemotherapy; (2) Patients with symptomatic brain metastases (symptoms of brain metastases remain clinically stable for at least 1 month after treatment, and no steroids and anticonvulsants can be enrolled for at least 1 month before entering the study); (3) Presence of clinically uncontrollable pleural effusion/ascites effusion (patients who do not need to drain the effusion or who have stopped draining for 3 days without a significant increase in effusion can be enrolled); (4) have not recovered adequately from toxicity and/or complications caused by any intervention (i.e., ≤ grade 1 or to baseline, excluding fatigue or alopecia, prior to initiation of treatment); (5) Diagnosis of other malignant tumors within 5 years before the first dose, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ that has undergone radical resection, if other malignant tumors or lung cancer are diagnosed more than 5 years before administration, pathological or cytological diagnosis of recurrent metastatic lesions is required; (6) Active hemoptysis, active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and peritoneal metastasis requiring clinical intervention; (7) Received solid organ or blood system transplantation; (8) Class III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmia; (9) Active autoimmune disease requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are not considered systemic therapy; (10) Patients who need long-term systemic use of corticosteroids (patients who need intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroids due to COPD and asthma can be enrolled); (11) History of non-infectious pneumonitis requiring corticosteroid treatment within 1 year before the first dose; (12) Have an active infection requiring treatment or have used systemic anti-infective drugs within one week before the first dose; (13) Known psychiatric illness or substance abuse that may affect compliance with trial requirements; (14) Those who are considered unsuitable for inclusion by the investigator.

研究实施时间：

Study execute time：

从 From 2024-07-15 00:00:00至 To 2026-07-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-11-01 00:00:00 至 To 2026-07-01 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	22
Group：	Test group	Sample size：	22
干预措施：	地舒单抗+替雷利珠单抗+多西他赛	干预措施代码：
Intervention：	Denosumab + tislelizumab + docetaxel	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)：	杨浦区
Country：	China	Province：	Shanghai	City：	Yangpu district
单位(医院)：	上海市肺科医院	单位级别：	三甲
Institution hospital：	Shanghai pulmonary hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	无进展生存期	指标类型：	主要指标
Outcome：	progress 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：	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：

指标中文名：	客观缓解率	指标类型：	主要指标
Outcome：	objective response 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：	疾病控制率	指标类型：	次要指标
Outcome：	Disease control 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：	缓解持续时间	指标类型：	次要指标
Outcome：	Duration of remission	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：	粪便	组织：
Sample Name：	Feces	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：	肿瘤组织	组织：
Sample Name：	Tumor tissue	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		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）：

无

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

Not applicable

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）：	文献发表
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Research 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：	电子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Electronic Data Capture
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：	2024-10-28 09:23:06