ChiCTR2200064690 版本V1.3 版本创建时间2023/05/02 09:41:54 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：

 ChiCTR2200064690 

最近更新日期：

Date of Last Refreshed on：

 2023-04-23 16:45:14 

注册时间：

Date of Registration：

 2022-10-14 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

肿瘤代谢调节联合免疫检查点抑制剂提高非小细胞肺癌治疗效果的临床研究

Public title：

Clinical study of tumor metabolism regulation combined with immune checkpoint inhibitors to improve the therapeutic effect of non-small cell lung cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

肿瘤代谢调节联合免疫检查点抑制剂提高非小细胞肺癌治疗效果的临床研究

Scientific title：

Clinical study of tumor metabolism regulation combined with immune checkpoint inhibitors to improve the therapeutic effect of 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：

陈梦婷 

研究负责人：

余慧青 

Applicant：

Chen Mengting 

Study leader：

Yu huiqing 

申请注册联系人电话：

Applicant telephone：

 17723159622

研究负责人电话：

Study leader's
telephone：

15909391166

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：

 chenmengting@cqu.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

 yhqdyx@cqu.edu.cn

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：

中国重庆市沙坪坝区汉渝路181号

研究负责人通讯地址：

中国重庆市沙坪坝区汉渝路181号

Applicant address：

No. 181 Hanyu Road, Shapingba District, Chongqing 400030, P. R. China.

Study leader's address：

No. 181 Hanyu Road, Shapingba District, Chongqing 400030, P. R. China.

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：

重庆大学附属肿瘤医院

Applicant's institution：

Chongqing University Cancer Hospital

研究负责人所在单位：

重庆大学附属肿瘤医院

Affiliation of the Leader：

Chongqing University Cancer 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：

 CZLS2021042-A

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：

重庆大学附属肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Chongqing University Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2021-02-04 00:00:00

伦理委员会联系人：

汤晓华

Contact Name of the ethic committee：

Tang Xiaohua

伦理委员会联系地址：

重庆市沙坪坝区汉渝路181号

Contact Address of the ethic committee：

No. 181 Hanyu Road, Shapingba District, Chongqing 400030, P. R. China.

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 23 65075696

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 czll6545@126.com

研究实施负责（组长）单位：

重庆大学附属肿瘤医院

Primary sponsor：

Chongqing University Cancer Hospital

研究实施负责（组长）单位地址：

重庆市沙坪坝区汉渝路181号

Primary sponsor's address：

181 Hanyu Road, Shapingba District, Chongqing 400030, P. R. China.

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

重庆

市(区县)：

沙坪坝

Country：

China

Province：

Chongqing

City：

Shapingba

单位(医院)：

重庆大学附属肿瘤医院

具体地址：

重庆市沙坪坝区汉渝路181号

Institution
hospital：

Chongqing University Cancer Hospital

Address：

181 Hanyu Road, Shapingba District, Chongqing

经费或物资来源：

重庆市科学技术局

Source(s) of funding：

Chongqing Science and Technology Bureau

研究疾病：

非小细胞肺癌  

Target disease：

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：

 上市后药物 

Study phase：

4

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

本研究旨在评价高浓缩复合乳酸菌代谢物质JK-5G联合免疫检查点抑制剂治疗IIIB/IV期非小细胞肺癌的疗效、不良反应发生率。  

Objectives of Study：

This study aim to evaluate the effect and the incidence of adverse reactions of microecological preparation JK-5G plus immune checkpoint inhibitor treatment in IIIB/IV stage non-small cell lung cancer patients.

药物成份或治疗方案详述：

非鳞NSCLC方案：选用（注射用培美曲塞二钠+顺铂注射液/卡铂注射液）+注射用卡瑞利珠单抗×4周期； 鳞癌NSCLC方案：选用（紫杉醇注射液+顺铂注射液/卡铂注射液）+替雷利珠单抗注射液 ×4周期。 

Description for medicine or protocol of treatment in detail：

Non scale NSCLC scheme: select (pemetrexed disodium for injection+cisplatin injection/carboplatin injection)+carelizumab for injection * 4 cycles; NSCLC scheme for squamous cell carcinoma: select (paclitaxel injection+cisplatin injection/carboplatin injection)+tirelizumab injection * 4 cycles. 

纳入标准：

1.组织学或细胞学确诊为非小细胞肺癌，分期为IIIB/IV期肿瘤（按照国际肺癌研究协会（IASLC）胸部肿瘤分期手册第8版判断），基因检测提示无驱动基因，EGFR、ALK、ROS1基因检测阴性。
2.年龄：18 - 75岁，男女均可。
3.东部肿瘤协作组（ECOG）体力状况评分为0 - 1。
4.预期寿命 ≥ 12周。
5.可评估疾病，根据实体瘤疗效评估标准（RECIST 1.1），至少有一个可测量病灶。
6.受试者未曾接受过手术、化学治疗、放射治疗及生物治疗的初治非小细胞肺癌；
7.育龄期男女患者在进入试验前、研究过程中直到停药后 8 周内都同意采用可靠方法避孕。
8.患者可正常经口进食。
9.受试者自愿加入本研究，签署知情同意书，依从性好，配合随访。

Inclusion criteria

1. Patients with non-small cell lung cancer confirmed by histopathology or cytology,confirmed stage IIIB–IV NSCLC (according to WHO 2015 classification); (IASLC) Thoracic Tumor Staging Manual, 8th Edition); and the primary tumor or lymph node metastases are clearly negative for EGFR/ALK/ROS1.
2. At the time of signing the informed consent, the age is >=18 years old and <=75 years old, male or female
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
4. The expected survival period is not less than 12 weeks
had no previous systemic chemotherapy, had at least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1), had Eastern Cooperative Oncology Group performance status of 0 or 1, and had a life expectancy of at least 3 months.
5.Evaluable disease with at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
6. Subjects who have not received surgery, chemotherapy, radiation therapy and biological therapy for newly diagnosed non-small cell lung cancer;
7. Male and female patients of childbearing age agree to use reliable methods of contraception before entering the trial, during the study, and within 8 weeks after stopping the drug;
8. Subjects can be normal to eat through the mouth.
9. Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.

排除标准：

1.无法正常经口进食者；
2.既往接受过任何T细胞共刺激或免疫检查点治疗，包括但不限于细胞毒性T淋巴细胞相关抗原-4（CTLA-4）抑制剂、PD-1抑制剂、PD-L1/2抑制剂或其他靶向T细胞的药物；
3.已知无法控制的或有症状的活动性中枢神经系统（CNS）转移，表现为出现临床症状、脑水肿、脊髓压迫、癌性脑膜炎、软脑膜疾病和/或进展性生长。有中枢神经系统转移或脊髓压迫病史的患者，如果明确接受过治疗且在研究首次给药前停用抗惊厥药和类固醇4周后临床表现稳定，则可以入组研究。
4.具有症状的、已播散到内脏的、短期内有出现危及生命的并发症风险的晚期患者（包括有无法控制的大量渗出液[胸腔、心包、腹腔]的患者）；
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）、药物诱导的肺炎、需要类固醇治疗的放射性肺炎或有临床症状的活动性肺炎；或其他严重影响肺功能的中重度肺部疾病（放射区存在放射性肺炎（纤维化）病史的患者可参加本研究）；
6.存在任何活动性自身免疫病或有自身免疫病病史且预期复发（包括但不局限于：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[仅通过激素替代治疗可以控制的受试者可纳入]；受试者患有无需全身治疗的皮肤病如白癜风、银屑病、脱发、I 型糖尿病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；需要支气管扩张剂进行医学干预的哮喘患者则不能纳入）。
7.活动性肺结核或筛选前≤48周内有活动性肺结核感染病史的受试者，无论是否治疗；
8.随机化时存在重度感染，包括但不仅限于需住院治疗的感染并发症、菌血症、重症肺炎等；
9.进入研究前的6个月内，出现以下情况：心肌梗死、严重/不稳定型心绞痛、NYHA 2级以上心功能不全以及有临床意义的室上性或室性心律失常而需要临床干预的患者；
10.HBsAg阳性且HBV DNA拷贝数大于所在研究中心检验科正常值上限（1000拷贝数/ml或500IU/ml ），或HCV阳性（HCV RNA或HCV Ab检测提示急慢性感染）；已知HIV阳性病史或已知的获得性免疫缺陷综合征（AIDS）；
11.进入研究前2年内曾患有其他活动性恶性肿瘤。可进行局部治疗且已治愈的皮肤基底细胞癌或鳞状细胞癌、浅表性膀胱癌、宫颈原位癌、乳腺导管内原位癌和甲状腺乳头状癌除外。
12.在随机前28天内接受过大型手术，或计划在研究期间接受大型手术；
13.首次研究药物治疗前28天内接受抗肿瘤治疗（包括化疗、放疗、免疫治疗、内分泌治疗、靶向治疗、生物治疗或者肿瘤栓塞术）；对于接受丝裂霉素和亚硝基脲治疗的患者不足6周者。
14.随机前28天内使用减毒活疫苗，或预计研究期间需要使用此种减毒活疫苗（随机前4周、治疗期间以及免疫检查点抑制剂末次给药后5个月内患者不允许接种流感减毒活疫苗）；
15.首次研究药物治疗前7天之内既往使用过免疫抑制药物，不包括喷鼻和吸入性皮质类固醇或生理剂量的系统性类固醇激素（即不超过10 mg/d泼尼松或同等药物生理学剂量的其他皮质类固醇）。
16.首次给药前4周内参与过任何其他药物临床研究，或距离末次研究用药不超过5个半衰期；
17.既往接受过同种异体骨髓移植或实体器官移植的患者；
18.已知对研究药物或辅料过敏，已知对任何一种单抗发生严重过敏反应；
19.已知有精神疾病、酗酒、无法戒烟、吸毒或药物滥用等情况；
20.经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素，如，不依从方案、其他的严重疾病（含精神疾病）需要合并治疗，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到受试者的安全，或资料及样品的收集。

Exclusion criteria：

1. Unable to eat normally through mouth;
2. Previous treatment with any T cell costimulation or immune checkpoint therapy, including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor, PD-1 inhibitor, PD-L1/2 inhibitor, or other T cell-targeting agent;
3. Known uncontrolled or symptomatic active central nervous system (CNS) metastases, manifested by the onset of clinical symptoms, cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, and/or progressive growth. Patients with a history of central nervous system metastases or spinal cord compression were eligible if they were clearly treated and clinically stable after 4 weeks of discontinuation of anticonvulsants and steroids before the first study dose.
4. Advanced patients with symptoms, who have disseminated to the viscera, and who are at risk for life-threatening complications in the short term (including patients with uncontrolled amounts of exudate [chest, pericardium, abdominal cavity]);
5. A history of idiopathic pulmonary fibrosis, organized pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonia, radiation pneumonitis requiring steroid treatment, or clinically active pneumonia; Or other moderate-to-severe lung disease that seriously affects lung function (patients with a history of radiation pneumonitis (fibrosis) in the radiation area can participate in this study);
6. there is no active autoimmune disease or a history of autoimmune disease recurrence and expectations (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, the pituitary gland inflammation, vasculitis, nephritis, thyroid function, thyroid function decrease [just by hormone replacement therapy can control subjects can be incorporated into]; Subjects with skin diseases that do not require systemic treatment such as vitiligo, psoriasis, alopecia, type I diabetes, or asthma that had completely resolved in childhood and did not require any intervention as adults were included; Patients with asthma requiring medical intervention with bronchodilators were excluded).
7. Subjects with active pulmonary tuberculosis or a history of active pulmonary tuberculosis infection within 48 weeks before screening, whether treated or not;
8. Severe infection at the time of randomization, including but not limited to infection complications requiring hospitalization, bacteremia, severe pneumonia, etc.;
9. Patients with myocardial infarction, severe/unstable angina pectoris, NYHA grade 2 or higher cardiac dysfunction, and clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention in the 6 months prior to study entry;
10. HBsAg positive and HBV DNA copy number greater than the upper limit of normal value (1000 copies /ml or 500IU/ml), or HCV positive (HCV RNA or HCV Ab test indicates acute or chronic infection); A known history of HIV positivity or known acquired immunodeficiency syndrome (AIDS);
11. Had other active malignant tumors within 2 years prior to study entry. Exceptions are basal or squamous cell carcinoma of the skin that can be treated locally and has been cured, superficial bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary carcinoma of the thyroid.
12. Had undergone major surgery within 28 days before randomization or was scheduled to undergo major surgery during the study period;
13. Received antitumor therapy (including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy, biotherapy, or tumor embolization) within 28 days before the first study drug therapy; For patients treated with mitomycin and nitrourea for less than 6 weeks.
14. Use of live attenuated vaccine within 28 days prior to randomization, or the anticipated need for such live attenuated vaccine during the study (patients were not allowed to receive live attenuated influenza vaccine during the 4 weeks prior to randomization, during treatment, or for 5 months after the last dose of an immune checkpoint inhibitor);
15. Prior use of immunosuppressive agents within 7 days prior to drug treatment for the first study, excluding nasal and inhaled corticosteroids or systemic steroid hormones at physiological doses (i.e., other corticosteroids not exceeding 10 mg/ day of prednisone or an equivalent physiologic dose).
16. Participated in any other drug clinical study within 4 weeks before the first drug administration, or no more than 5 half-lives since the last drug administration;
17. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
18. Known allergy to study drugs or excipients, known severe allergic reaction to any mab;
19. Known mental illness, alcohol abuse, inability to quit smoking, drug or substance abuse;
20. judging by the researchers, the participants have other factors that may result in this study were forced to midway termination, such as, nonadherence scheme, other serious disease (including mental illness) need to merge treatment, there are serious abnormal laboratory examination, accompanied by factors such as family or society, will affect the safety of the subjects, or information and the collection of the sample.

研究实施时间：

Study execute time：

从 From 2021-01-01 00:00:00至 To 2024-12-31 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：

对照组

样本量：

 20

Group：

Control

Sample size：

干预措施：

PD-1 联合化疗

干预措施代码：

Intervention：

PD-1 plus chemotherapy

Intervention code：

组别：

试验组

样本量：

 20

Group：

Intervention group

Sample size：

干预措施：

PD-1 联合化疗+肠道微生态制剂JK-5G

干预措施代码：

Intervention：

PD-1 plus chemotherapy plus microecological preparation JK-5G

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 重庆 

市(区县)：

 沙坪坝 

Country：

China

Province：

Chongqing

City：

Shapingba

单位(医院)：

 重庆大学附属肿瘤医院 

单位级别：

 三甲 

Institution
hospital：

Chongqing University Cancer 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：

Progression 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：

主要指标

Outcome：

Overall 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：

生存质量

指标类型：

次要指标

Outcome：

Quality Of Life

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

有效缓解率

指标类型：

次要指标

Outcome：

Objective Response 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：

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：

不良反应发生率

指标类型：

次要指标

Outcome：

Adverse Effects 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：

CD4+/CD8+ T淋巴细胞计数

指标类型：

次要指标

Outcome：

CD4 + / CD8 + T lymphocytes count

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肠道菌群16s DNA测序

指标类型：

次要指标

Outcome：

16S DNA sequencing of gut microbiota

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

血液炎性因子

指标类型：

次要指标

Outcome：

Blood inflammatory cytokines

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：

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：

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）：

合格患者将采用随机数字表进行随机分组，利用SAS统计分析系统产生随机数字表，所有入组研究对象按照随机数字表分派的随机数字进行随机分组；由统计分析方统一分派随机数字并确定随机分组方案；

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

using random number table

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

单盲

Blinding：

Single blind

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）：

原始数据公开至中国临床试验注册中心 http://www.chictr.org.cn

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

Raw data released to China Clinical Trial Center（ http://www.chictr.org.cn）

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：

采用电子采集和管理系统(Electronic Data Capture, EDC)

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：

有/Yes

注册人：

Name of Registration：

  2022-10-14 17:46:32