ChiCTR2200065238 版本V1.2 版本创建时间2023/04/27 19:54:22 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：

 ChiCTR2200065238 

最近更新日期：

Date of Last Refreshed on：

 2022-11-02 11:00:33 

注册时间：

Date of Registration：

 2022-11-01 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

安罗替尼联合派安普利单抗与化疗一线治疗广泛期小细胞肺癌：一项单臂、前瞻性临床研究

Public title：

Anlotinib combined with penpulimab and chemotherapy for first-line treatment of extensive stage small cell lung cancer: a single-arm, prospective clinical study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

安罗替尼联合派安普利单抗与化疗一线治疗广泛期小细胞肺癌：一项单臂、前瞻性临床研究

Scientific title：

Anlotinib combined with penpulimab and chemotherapy for first-line treatment of extensive stage small cell lung cancer: a single-arm, prospective clinical study

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：

赵晓丽 

研究负责人：

孔天东 

Applicant：

Xiaoli Zhao 

Study leader：

Tiandong Kong 

申请注册联系人电话：

Applicant telephone：

 177 0394 2588

研究负责人电话：

Study leader's
telephone：

133 8384 9341

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：

 ZhaoxiaoLi2048@163.com

研究负责人电子邮件：

Study leader's E-mail：

 kongtiandong@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：

河南省郑州市管城回族区区南顺城街136号

研究负责人通讯地址：

河南省郑州市管城回族区南顺城街136号

Applicant address：

136 Nanshuncheng Street, Guancheng Hui District, Zhengzhou City, Henan Province

Study leader's address：

136 Nanshuncheng Street, Guancheng Hui District, Zhengzhou City, Henan Province

申请注册联系人邮政编码：

Applicant postcode：

 450000

研究负责人邮政编码：

Study leader's postcode：

 450000

申请人所在单位：

郑州市第三人民医院

Applicant's institution：

The Third People's Hospital of Zhengzhou

研究负责人所在单位：

郑州市第三人民医院

Affiliation of the Leader：

The Third People's Hospital of Zhengzhou

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：

 SY20220218

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：

郑州市第三人民医院人体试验伦理委员会

Name of the ethic committee：

Human Experimental Ethics Committee of the Third People's Hospital of Zhengzhou

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-03-04 00:00:00

伦理委员会联系人：

李瑞

Contact Name of the ethic committee：

Rui Li

伦理委员会联系地址：

河南省郑州市管城回族区南顺城街136号

Contact Address of the ethic committee：

136 Nanshuncheng Street, Guancheng Hui District, Zhengzhou City, Henan Province

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：

郑州市第三人民医院

Primary sponsor：

The Third People's Hospital of Zhengzhou

研究实施负责（组长）单位地址：

河南省郑州市管城回族区南顺城街136号

Primary sponsor's address：

136 Nanshuncheng Street, Guancheng Hui District, Zhengzhou City, Henan Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

河南

市(区县)：

郑州

Country：

China

Province：

Henan

City：

Zhengzhou

单位(医院)：

郑州市第三人民医院

具体地址：

河南省郑州市管城回族区南顺城街136号

Institution
hospital：

The Third People's Hospital of Zhengzhou

Address：

136 Nanshuncheng Street, Guancheng Hui District, Zhengzhou City, Henan Province

经费或物资来源：

自筹

Source(s) of funding：

self-raised

研究疾病：

小细胞肺癌  

Target disease：

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：

单臂 

Study design：

Single arm 

研究目的：

观察和评价派安普利单抗联合安罗替尼和化疗治疗广泛期小细胞肺癌的有效性和安全性  

Objectives of Study：

To observe and evaluate the efficacy and safety of pembrolizumab combined with anlotinib and chemotherapy in the treatment of extensive stage 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.年龄：18岁～75岁；
2.经组织学或细胞学确诊的广泛期小细胞肺癌；
3.既往未接受过针对广泛期小细胞肺癌的系统治疗
4.ECOG评分：0-2分；
5.预计生存期 ≥ 3月；
6.具有可测量病灶（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，扫描层厚不大于5mm，可测量病灶未接受过放疗、冷冻等局部治疗）；
7.主要器官功能正常，即符合下列标准：
（1）血常规检查标准需符合（14天内未输血及血制品，未使用G-CSF及其他造血刺激因子纠正）：
a.血红蛋白（HB）≥90 g/L；
b.中性粒细胞绝对值（ANC）≥1.5×109/L；
c.血小板（PLT）≥80×109/L；
（2）生化检查需符合以下标准：
a.总胆红素（TBIL）<1.5ULN；
b.谷丙转氨酶（ALT）及谷草转氨酶（AST）<2.5ULN，而对于肝转移患者则< 5ULN；
c.血清肌酐（Cr）≤1.25ULN或内生肌酐清除率> 50 ml/min（Cockcroft-Gault公式）；
8. 育龄妇女必须已经采取可靠的避孕措施或在入组前7天内进行妊娠试验（血清或尿液），且结果为阴性，并且愿意在试验期间和末次给予试验药物后8周采用适当的方法避孕。对于男性，须同意在试验期间和末次给予试验药物后8周采用适当的方法避孕或已手术绝育；
9. 受试者自愿加入本研究，并签署知情同意书，依从性好，配合随访。

Inclusion criteria

1. Age: 18~75 years old;

2. Extensive stage small cell lung cancer confirmed by histology or cytology;

3. No previous systematic treatment for extensive stage small cell lung cancer

4.ECOG score: 0-2;

5. Predicted survival ≥ 3 months;

6. Measurable lesions (according to RECIST 1.1 criteria, the CT scan diameter of tumor lesions is ≥10mm, the CT scan diameter of lymph node lesions is ≥15mm, the scan thickness is not more than 5mm, and the lesions can be measured without local treatment such as radiotherapy or freezing);

7. Normal function of major organs means that the following criteria are met:

(1) The standard of blood routine examination should be met (no blood transfusion or blood products, no G-CSF or other hematopoietic stimulating factors were used for correction within 14 days) :

A. Hemoglobin (HB) ≥90 g/L;

B. Neutrophil absolute value (ANC) ≥1.5×109/L;

C. Platelet (PLT) ≥80×109/L;

(2) Biochemical tests shall meet the following standards:

A. Total bilirubin (TBIL) & LT; 1.5 ULN;

B. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) & LT; 2.5ULN, and & LT for patients with liver metastases; 5 uln;

C. Serum creatinine (Cr) ≤1.25ULN or endogenous creatinine clearance & GT; 50 ml/min (Cockcroft-Gault formula);

8. Women of reproductive age must have used reliable contraception or had a pregnancy test (serum or urine) with negative results within 7 days before enrollment and be willing to use appropriate methods of contraception during the trial and 8 weeks after the last administration of the trial drug. For men, consent to use appropriate methods of contraception or have been surgically sterilized during the trial period and for 8 weeks after the last administration of the trial drug;

9. The subjects volunteered to join the study and signed the informed consent. They had good compliance and cooperated with follow-up.

排除标准：

1. 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；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)；
2. 存在活动性感染，比如：活动性乙肝（慢性或急性；定义为筛选期乙肝病毒表面抗原 [HBsAg] 检测结果呈阳性）或丙肝患者，既往乙肝病毒（HBV）感染或HBV感染已治愈的患者（定义为乙型肝炎核心抗体[HBcAb]阳性且HBsAg阴性），可参与本项研究。在入组前，必须获得此类患者HBV DNA的检测结果。丙肝病毒（HCV）抗体呈阳性的患者中，仅聚合酶链反应（PCR）显示HCV RNA呈阴性的患者可参与本项研究；HIV检测结果呈阳性；活动性肺结核；
3. 患有严重的心血管疾病，如纽约心脏学会心脏疾病（II级或更高）、随机分配前3个月内发生的心肌梗死、脑血管意外 、不稳定性心律失常、不稳定型心绞痛，已知患有冠状动脉疾病、不符合上述标准的充血性心力衰竭、或左心室射血分数 < 50%的患者，必须接受治疗医生认为最佳的稳定治疗方案治疗，必要时可咨询心脏病专家；
4.筛选期和和既往影像学评估，经计算机断层扫描（CT）或磁共振成像（MRI）检测发现活动性或未治疗的CNS转移灶和/或癌性脑膜炎；
5.患有特发性肺纤维化病史、机化性肺炎（如闭塞性细支气管炎）、药物性肺炎、特发性肺炎或筛选时胸部CT扫描显示活动性肺炎证据，放射区存在放射性肺炎（纤维化）病史的患者可参与本研究；
6.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；
7.既往接受过同种异体骨髓移植或实体器官移植的患者；
8.有明确药物过敏史或属过敏体质者，对嵌合或人源化抗体或融合蛋白有严重变应性、过敏反应或对依托泊苷/铂类过敏；
9.在入选治疗前6个月内发生过任何动脉血栓、栓塞或缺血，如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作等。在入组前3个月内有深静脉血栓、肺栓塞或其它任何严重血栓栓塞的病史（植入式静脉输液港或导管源性血栓形成，或浅表静脉血栓形成不被视为“严重”血栓栓塞）；
10.影像学显示肿瘤已侵犯重要血管周或经研究者判断患者肿瘤在治疗期间有极高可能侵袭重要血管而引起致命大出血的情况；
11.经降压药物治疗无法获得良好控制的高血压患者(收缩压≥140 mmHg 或者舒张压≥90 mmHg)；
12.须满足：在不使用抗凝剂的情况下INR在正常值范围内）；应用抗凝剂或维生素K 拮抗剂如华法林、肝素或其类似物治疗的患者；在凝血酶原时间国际标准化比值（INR）≤ 1.5的前提下，允许以预防目的使用小剂量华法林（1 mg口服，每日一次）或小剂量阿司匹林（每日用量不超过100 mg）；
13.存在限制遵守研究要求、显著增加发生AE风险或影响患者提供书面知情同意书能力的精神疾病/社会情况；
14.哺乳期女性；
15.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；
16.研究者判定其他不适合纳入研究的情况。

Exclusion criteria：

1. The subject has any active autoimmune disease or a history of autoimmune disease (e.g., but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Subjects with vitiligo or complete remission of asthma in childhood without any intervention as adults were included; Subjects with asthma requiring medical intervention with bronchodilators were excluded);

2. The presence of active infections, such as active hepatitis B (chronic or acute; Patients who were previously infected with or cured of hepatitis B virus (HBV) infection (defined as HBcAb positive and HBsAg negative) or hepatitis C during the screening period were eligible for participation. Before enrollment, HBV DNA test results must be obtained from such patients. Among patients who were antibody positive for hepatitis C virus (HCV), only those who were negative for HCV RNA by polymerase chain reaction (PCR) were eligible for participation; Test positive for HIV; Active pulmonary tuberculosis;

(3) with severe cardiovascular disease, heart disease, such as New York heart association (class II or higher), randomly assigned three months before the occurrence of myocardial infarction, cerebrovascular accident, instability, unstable angina, arrhythmia, with known coronary artery disease, do not accord with standard of the congestive heart failure, or left ventricular ejection fraction & lt; 50% of patients must be treated with a stable regimen that the treating physician considers optimal, with consultation with a cardiologist if necessary;

4. Active or untreated CNS metastases and/or cancerous meningitis detected by computed tomography (CT) or magnetic resonance imaging (MRI) during the screening period and prior imaging evaluation;

5. Patients with a history of idiopathic pulmonary fibrosis, organized pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, or evidence of active pneumonia on chest CT scan at screening and a history of radiation pneumonitis (fibrosis) in the radiation area were eligible to participate in this study;

6. Patients requiring long-term systemic corticosteroid use. Patients with COPD or asthma requiring intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections were enrolled.

7. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;

8. Severe allergic reaction or allergic reaction to chimeric or humanized antibodies or fusion proteins or allergic reaction to etoposide/platinum in patients with definite history of drug allergy or allergic constitution;

9. Any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, occurred in the 6 months prior to enrollment. A history of deep vein thrombosis, pulmonary embolism, or any other major thromboembolism in the 3 months prior to enrollment (implantable venous port or catheter-derived thrombosis, or superficial venous thrombosis is not considered "severe" thromboembolism);

10. Imaging shows that the tumor has invaded the periphery of important blood vessels or is judged by the investigator to be highly likely to invade important blood vessels and cause fatal massive bleeding during treatment;

11. Patients with hypertension that is not well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);

12. INR shall be within the normal range without the use of anticoagulants); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues; Low-dose warfarin (1 mg orally, once daily) or low-dose aspirin (not more than 100 mg daily) is allowed for prophylaxis if the international normalized ratio of prothrombin time (INR) is 1.5 or less;

13. Mental illness/social condition that limits compliance with study requirements, significantly increases the risk of AE, or affects the patient's ability to provide written informed consent;

14. Lactating women;

15. There is a known mental illness or substance abuse that may affect compliance with trial requirements;

16. Other conditions determined by the investigator to be inappropriate for inclusion in the study.

研究实施时间：

Study execute time：

从 From 2022-11-01 00:00:00至 To 2024-10-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-11-01 00:00:00 至 To 2024-10-31 00:00:00

干预措施：

Interventions：

组别：

单臂

样本量：

 30

Group：

Single arm

Sample size：

干预措施：

安罗替尼联合派安普利单抗和化疗

干预措施代码：

Intervention：

Anlotinib plus penpulimab and chemotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 河南 

市(区县)：

 郑州 

Country：

China

Province：

Henan

City：

Zhengzhou

单位(医院)：

 郑州市第三人民医院 

单位级别：

 三级综合医院 

Institution
hospital：

The Third People's Hospital of Zhengzhou

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：

PFS

Type：

Primary 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：

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：

总生存期

指标类型：

次要指标

Outcome：

OS

Type：

Secondary 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：

DCR

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

指标类型：

次要指标

Outcome：

Security

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：

尚未开始

Not yet 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）：

无

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

NONE

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）：

RESMAN:http://www.medresman.org.cn/login.aspx

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

RESMAN:http://www.medresman.org.cn/login.aspx

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：

有/Yes

注册人：

Name of Registration：

  2022-11-01 15:23:14