ChiCTR2100053353 版本V1.0 版本创建时间2021/11/20 09:37:52 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：

 ChiCTR2100053353 

最近更新日期：

Date of Last Refreshed on：

 2021-11-20 09:37:46 

注册时间：

Date of Registration：

 2021-11-20 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

三天持续静脉泵注重组人血管内皮抑制素（恩度）联合信迪利单抗和含铂双药一线治疗晚期非小细胞肺癌临床研究

Public title：

A trial of three-day continuous Osmotic Pump of endostar combined with platinum-based chemotherapy plus Sindilizumab? for treatment? 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：

三天持续静脉泵注重组人血管内皮抑制素（恩度）联合信迪利单抗和含铂双药一线治疗晚期非小细胞肺癌临床研究

Scientific title：

A trial of three-day continuous Osmotic Pump of endostar combined with platinum-based chemotherapy plus Sindilizumab? for treatment? 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：

温友利 

研究负责人：

邓治平 

Applicant：

Youli Wen 

Study leader：

Zhiping Deng 

申请注册联系人电话：

Applicant telephone：

 13629020677

研究负责人电话：

Study leader's
telephone：

13608158051

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：

 165178713@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 13608158051@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：

四川省自贡市自流井区尚义灏一支路42号

研究负责人通讯地址：

四川省自贡市自流井区尚义灏一支路42号

Applicant address：

No.42, Shangyihao First Branch Road, Ziliujing District, Zigong City, Sichuan Province

Study leader's address：

No.42, Shangyihao First Branch Road, Ziliujing District, Zigong City, Sichuan Province

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：

四川省自贡市第一人民医院

Applicant's institution：

Zigong First People's Hospital, Sichuan Province

研究负责人所在单位：

Affiliation of the Leader：

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：

 自贡市第一人民医院伦理（研）2021年第59号

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：

自贡市第一人民医院伦理委员会

Name of the ethic committee：

Ethics Committee of Zigong First People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2021-09-18 00:00:00

伦理委员会联系人：

郭祖秀

Contact Name of the ethic committee：

Zuxiu Guo

伦理委员会联系地址：

四川省自贡市自流井区尚义灏一支路42号

Contact Address of the ethic committee：

No.42, Shangyihao First Branch Road, Ziliujing District, Zigong City, Sichuan 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：

四川省自贡市第一人民医院

Primary sponsor：

Zigong First People's Hospital, Sichuan Province

研究实施负责（组长）单位地址：

四川省自贡市自流井区尚义灏一支路42号

Primary sponsor's address：

No.42, Shangyihao First Branch Road, Ziliujing District, Zigong City, Sichuan 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)：

四川省

市(区县)：

自贡市

Country：

China

Province：

Sichuan Province

City：

Zigong City

单位(医院)：

四川省自贡市第一人民医院

具体地址：

四川省自贡市自流井区尚义灏一支路42号

Institution
hospital：

Zigong First People's Hospital, Sichuan Province

Address：

No.42, Shangyihao First Branch Road, Ziliujing District, Zigong City, Sichuan Province

经费或物资来源：

四川省自贡市第一人民医院

Source(s) of funding：

Zigong First People's Hospital, Sichuan Province

研究疾病：

肺癌  

Target disease：

lung caner

研究疾病代码：

C08

Target disease code：

C08

研究类型：

预后研究

Study type：

Prognosis study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评估三天持续静脉泵注恩度联合信迪利单抗和含铂双药一线治疗晚期驱动基因阴性非小细胞肺癌的疗效和安全性，同时了解治疗前后患者免疫功能的变化，以及分析初始T细胞亚群水平的异常对晚期驱动基因阴性非小细胞肺癌使用含铂化疗联合恩度及信迪利单抗疗效的影响，从而初步了解初始T细胞亚群水平是否可以作为判定恩度联合免疫治疗疗效的指标。  

Objectives of Study：

To evaluate the efficacy and safety of three-day continuous intravenous pumping of Recombinant Human Endostain(or Endostar) in combination with Sintilimab and Platinum-containing duals in the First-line treatment of advanced Driver gene-negative non-small cell lung cancer(NSCLC), and to understand the changes in immune function of patients before and after treatment, as well as to analyze the impact of abnormal initial T-cell subpopulation levels on the efficacy of advanced NSCLC using platinum-containing chemotherapy in combination with Endostar and Sintilimab, so as to gain a preliminary understanding of whether initial T cell subpopulation levels can be used as an indicator of the efficacy of Endostar combination immunotherapy.

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)受试者自愿同意参加，并给予书面知情同意。
2)初治的IIIB-IV期NSCLC的受试者。
3)受试者EGFR或ALK驱动基因突变阴性。
4)既往未接受过针对晚期/转移性疾病的任何系统性抗肿瘤治疗。对于既往曾接受过含铂辅助/新辅助化疗，或针对进展期疾病接受过根治性放化疗的患者，如疾病进展或复发与末次化疗药物治疗结束间隔至少6个月以上，允许入组本研究。
5)根据实体肿瘤疗效评价标准（RECIST 1.1版），至少有一处影像学可测量病灶。
6)东部肿瘤协作组（ECOG）体能状态评分为0-1。
7)预期生存时间>3个月。
8)具有充分的器官和骨髓功能，入组前7天内实验室检查值符合下列要求(获得实验室检查的前14天内不允许给予任何血液成分、细胞生长因子、白蛋白及其他纠正治疗的药物)，具体如下：
9)血常规：中性粒细胞绝对计数（ANC）≥1.5×109/L，血小板（PLT）≥75×109/L，血红蛋白（HGB）≥90 g/L（14日内无输血或无促红细胞生成素依赖性）
10)肝功能：血清总胆红素（TBIL）≤2倍正常上限（ULN）；丙氨酸氨基转移酶（ALT）和/或天门冬氨酸氨基转移酶（AST）≤5倍ULN，血清白蛋白≥35 g/L；碱性磷酸酶（alkaline phosphatase, ALP）≤5×ULN。
11)肾功能：血清肌酐（Cr）≤1.5×ULN，或肌酐清除率≥50 mL/min（应用标准的 Cockcroft -Gault公式）：尿常规结果显示尿蛋白＜2+；对基线时尿常规检测显示尿蛋白≥2+的患者，应进行24小时尿液采集且24小时尿蛋白定量＜1g。
12)凝血功能：国际标准化比值（INR）或凝血酶原时间（PT）≤1.5倍ULN；若受试者正接受抗凝治疗，只要INR在抗凝药物拟定的使用范围内即可。
13)年龄≥18周岁且≤75周岁。
14)对于育龄期女性受试者，应在接受首次研究药物给药之前的3天进行尿液或血清妊娠试验且结果为阴性。
15)受试者与受试者性伴侣需要在研究治疗期间和研究治疗期结束后6个月内采用一种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套等）。

Inclusion criteria

1) Subjects voluntarily agreed to participate and gave written informed consent.
2)Subjects with primary treatment of stage IIIB-IV NSCLC.
3)Subjects are negative for EGFR or ALK driver mutations.
4)No prior systemic antitumor therapy for advanced/metastatic disease. Patients who have received prior platinum-containing adjuvant/neoadjuvant chemotherapy or radical radiotherapy for progressive disease are allowed to be enrolled in this study if at least 6 months have elapsed between disease progression or recurrence and the end of the last chemotherapeutic drug treatment.
5)At least one imaging measurable lesion according to Response Evaluation Criteria In Solid Tumors(RECIST version 1.1).
6)Eastern Collaborative Oncology Group (ECOG) physical status score of 0-1.
7)Expected survival time > 3 months.
8)Adequate organ and bone marrow function with laboratory test values within 7 days prior to enrollment meeting the following requirements (no blood components, cell growth factors, albumin and other corrective therapy medications are allowed to be given within the first 14 days of obtaining laboratory tests) as follows.
9) Blood routine: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets (PLT) ≥ 75 × 109/L, hemoglobin (HGB) ≥ 90 g/L (no transfusion or erythropoietin-dependent within 14 days)
10) Liver function: serum total bilirubin (TBIL) ≤ 2 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 5 times ULN, serum albumin ≥ 35 g/L; alkaline phosphatase (ALP) ≤ 5 × ULN.
11) Renal function: serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min (applying the standard Cockcroft -Gault formula): urine routine results showing urine protein <2+; for patients whose urine routine test shows urine protein ≥2+ at baseline, 24-hour urine collection and 24-hour urine protein quantification <1g should be performed.
12) Coagulation: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; if the subject is on anticoagulation therapy, as long as the INR is within the proposed range of anticoagulant medication.
13) Age ≥ 18 years and ≤ 75 years.
14) For female subjects of childbearing age, a negative urine or serum pregnancy test should be performed 3 days prior to receiving the first dose of study drug.
15) The subject and the subject's sexual partner are required to use a medically approved form of contraception (such as IUDs, birth control pills or condoms) during and for 6 months after the end of the study treatment period.

排除标准：

1)已知EGFR敏感突变或ALK重排阳性的患者；
2)影像学（CT或者MRI）显示肿瘤侵犯大血管者或经评估后预计后续研究期间肿瘤极有可能侵袭重要血管引起致命大出血者；
3)当前正在参与干预性临床研究治疗，或在首次给药前4周内接受过其他研究药物或研究器械治疗；
4)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，CTLA-4、OX-40、CD137）的药物；
5)首次给药前2周内接受过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），或首次给药前3周内接受过重大手术治疗；
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)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；
8)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；
9)已知对PD-1/L1单抗、重组人血管内皮抑制素活性成分和或任何辅料有过敏反应；
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)有症状的中枢神经转移。对于无症状脑转移或脑转移病灶经过治疗后症状稳定的患者，只要符合下列所有标准，可参与本项研究：中枢神经系统之外有可测量的病灶；无中脑、脑桥、小脑、脑膜、延髓或脊髓转移；保持临床稳定状态至少2周；首剂研究药物前3天停止激素治疗；
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)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）；
14)已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）；
15)未经治疗的活动性乙肝（定义为HBsAg阳性同时检测到HBV-DNA拷贝数大于所在研究中心检验科正常值上限）；
16)注：符合下列标准的乙肝受试者亦可入组：
17)首次给药前HBV病毒载量<1000拷贝/ml（200 IU/ml），受试者应在整个研究化疗药物治疗期间接受抗HBV治疗避免病毒再激活
18)对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活
19)活动性的HCV感染受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）；
20)首次给药之前（第1周期，第1天）30天内接种过活疫苗；
21)注：允许首次给药前30天内接受针对季节性流感的注射用灭活病毒疫苗；但是不允许接受鼻内用药的减毒活流感疫苗。
22)妊娠或哺乳期妇女；
23)有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况研究者认为存在其他潜在风险不适合参加本研究。

Exclusion criteria：

1) Patients with known EGFR-sensitive mutations or positive ALK rearrangements.
2) Those whose imaging (CT or MRI) shows tumor invasion of large blood vessels or those who, after evaluation, are expected to have a high likelihood of fatal hemorrhage due to tumor invasion of important blood vessels during the follow-up study.
3) Currently participating in an interventional clinical study treatment or have received another investigational drug or investigational device within 4 weeks prior to the first dose
4) Prior therapy with: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs targeting another stimulatory or synergistic inhibitor of T-cell receptors (e.g., CTLA-4, OX-40, CD137).
5) Have received a proprietary Chinese medicine with an antitumor indication or an immunomodulatory agent (thymidine, interferon, interleukin, etc.) within 2 weeks prior to the first dose, or have received major surgical treatment within 3 weeks prior to the first dose.
6) Presence of active hemoptysis, active diverticulitis, abdominal abscesses, gastrointestinal obstruction and peritoneal metastases requiring clinical intervention.
7) Class III-IV congestive heart failure (New York Heart Association Classification) with poorly controlled and clinically significant arrhythmias.
8) Any arterial thrombosis, embolism or ischemia such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack within 6 months prior to enrollment in therapy.
9) Known allergic reaction to PD-1/L1 monoclonal antibody, recombinant human vascular endothelial inhibitor active ingredient and or any excipients.
10) Patients requiring long-term systemic use of corticosteroids. Patients requiring intermittent use of bronchodilators, inhaled corticosteroids, or local injections of corticosteroids due to COPD, asthma may be enrolled.
11) Symptomatic central nervous metastases. Patients with asymptomatic brain metastases or treated brain metastases that are symptomatically stable may be enrolled in this study as long as all of the following criteria are met: measurable lesions outside the CNS; no midbrain, pontine, cerebellar, meningeal, medulla oblongata, or spinal cord metastases; maintenance of clinical steady state for at least 2 weeks; and discontinuation of hormone therapy 3 days prior to the first dose of study drug.
12) Have an active infection requiring treatment or have used systemic anti-infective drugs within one week prior to the first dose;
13) Have not recovered sufficiently from toxicity and/or complications from any intervention (i.e., ≤ grade 1 or at baseline, excluding malaise or alopecia) prior to initiation of treatment
14) Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibody).
15) Active untreated hepatitis B (defined as HBsAg positivity along with a detectable HBV-DNA copy number greater than the upper limit of normal values in the testing department of the study center).
16) Note: Subjects with hepatitis B who meet the following criteria may also be enrolled.
17) HBV viral load <1000 copies/ml (200 IU/ml) before the first dose, and subjects should receive anti-HBV therapy to avoid viral reactivation throughout the duration of the study chemotherapy drug treatment
18) For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring for viral reactivation is required
19) Active HCV-infected subjects (positive for HCV antibodies and HCV-RNA levels above the lower limit of detection).
20) Live vaccination within 30 days prior to the first dose (cycle 1, day 1)
21) Note: Receipt of live inactivated virus vaccine for seasonal influenza by injection within 30 days prior to the first dose is permitted; however, intranasal administration of live attenuated influenza vaccine is not permitted.
22) Women who are pregnant or breastfeeding.
23) Medical history or evidence of disease that may interfere with the results of the trial, prevent the subject from participating in the study throughout, abnormal treatment or laboratory test values, or other conditions that in the opinion of the investigator make enrollment unsuitable The investigator believes that there is other potential risk of unsuitability for participation in this study.

研究实施时间：

Study execute time：

从 From 2021-09-18 00:00:00至 To 2022-11-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2021-09-18 00:00:00 至 To 2021-12-27 00:00:00

干预措施：

Interventions：

组别：

三天持续静脉泵注重组人血管内皮抑制素（恩度）联合信迪利单抗和含铂双药组

样本量：

 20

Group：

three-day continuous Osmotic Pump of endostar combined with platinum-based chemotherapy plus Sindilizumab group

Sample size：

干预措施：

三天持续静脉泵注重组人血管内皮抑制素（恩度）联合信迪利单抗和含铂双药

干预措施代码：

Intervention：

three-day continuous Osmotic Pump of endostar combined with platinum-based chemotherapy plus Sindilizumab

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川省 

市(区县)：

 自贡市 

Country：

China

Province：

Sichuan Province

City：

Zigong City

单位(医院)：

 四川省自贡市第一人民医院 

单位级别：

 三级甲等 

Institution
hospital：

Zigong First People's Hospital, Sichuan Province

Level of the institution：

Third rate

测量指标：

Outcomes：

指标中文名：

肿瘤大小

指标类型：

主要指标

Outcome：

tumor size

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

T细胞亚群

指标类型：

次要指标

Outcome：

T cell subsets

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：

血液

Sample Name：

Blood

Tissue：

Blood

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）：

单臂法

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

single arm

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

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）：

2023年1月

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

In January 2023

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

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

Case Record Form

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2021-11-20 09:37:46