ChiCTR2000040962 版本V1.2 版本创建时间2021/04/05 11:32:55 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：

ChiCTR2000040962 

最近更新日期：

Date of Last Refreshed on：

2021-04-05 11:31:20 

注册时间：

Date of Registration：

2020-12-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

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。 评估度伐利尤单抗注射液联合化疗在非小细胞肺癌全程管理中的有效性和安全性II期研究方案

Public title：

A phase II study to evaluate the efficacy and safety of Durvalumab combined with chemotherapy in the whole process management 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：

评估度伐利尤单抗注射液联合化疗在非小细胞肺癌全程管理中的有效性和安全性II期研究方案

Scientific title：

A phase II study to evaluate the efficacy and safety of Durvalumab combined with chemotherapy in the whole process management 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：

王怀宇 

研究负责人：

王怀宇 

Applicant：

Huaiyu Wang 

Study leader：

Huaiyu Wang 

申请注册联系人电话：

Applicant telephone：

+86 18514289788

研究负责人电话：

Study leader's telephone：

+86 18514289788

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：

444584398@qq.com

研究负责人电子邮件：

Study leader's E-mail：

444584398@qq.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：

北京市海淀区阜成路30号

研究负责人通讯地址：

北京市海淀区阜成路30号

Applicant address：

30 Fucheng Road, Haidian District, Beijing

Study leader's address：

30 Fucheng Road, Haidian District, Beijing

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：

空军特色医学中心

Applicant's institution：

Air Force Medical Center

研究负责人所在单位：

空军特色医学中心

Affiliation of the Leader：

Air Force Medical Center

是否获伦理委员会批准：

否/No

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：

空军特色医学中心

Primary sponsor：

Air Force Medical Center

研究实施负责（组长）单位地址：

北京市海淀区阜成路30号

Primary sponsor's address：

30 Fucheng Road, Haidian District, Beijing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

空军特色医学中心

具体地址：

海淀区阜成路30号

Institution
hospital：

Air Force Special Medical Center

Address：

30 Fucheng Road, Haidian District

经费或物资来源：

自筹

Source(s) of funding：

self-raised

Target disease：

Patients with driver gene (EGFR/ALK/ROS1) -negative, unresectable stage II-IIIA (N2) NSCLC

Target disease code：

研究类型：

观察性研究

Study type：

Observational 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：

依据 RECIST1.1 标准，评价度伐利尤单抗注射液联合化疗在非小细胞肺癌全程管理中的12个月无事件生存率（EFS）。  

Objectives of Study：

To evaluate the event-free survival (EFS) rate at 12 months after treatment with Durvalumab combined with chemotherapy in the whole course of non-small cell lung cancer (NSCLC) according to RECIST 1.1.

药物成份或治疗方案详述：

受试者将全部术后接受度伐利尤单抗注射液联合化疗辅助治疗直至疾病进展死亡、毒性不可耐受或撤回知情同意书（以先出现者为准）。 根据RECIST1.1标准评估抗肿瘤客观疗效，从治疗开始每6周（+/-7天）进行一次肿瘤影像学评估，直至疾病进展、死亡、撤回知情同意或终止治疗。 

Description for medicine or protocol of treatment in detail：

Patients will receive all postoperative adjuvant therapy with Durvalumab in combination with chemotherapy until disease progression, death, unacceptable toxicity, or withdrawal of informed consent (whichever occurs first). To assess objective antitumor response according to RECIST 1.1, tumor imaging assessment will be performed every 6 weeks (+/- 7 days) from the start of treatment until disease progression, death, withdrawal of informed consent or treatment discontinuation. 

纳入标准：

1. 签署知情同意书；
2. 年龄＞18周岁；
3. 经组织学或细胞学确诊的非小细胞肺癌，且有根据RECIST1.1标准可测量的病灶；
4. ECOG 评分0-1；
5. 预期生存 ≥ 12周；
6. 纳入驱动基因(EGFR/ALK/ROS1)阴性、未经治疗的II A～III A(N2)期NSCLC患者
7. 患者在入组前，既往未接受抗血管生成小分子靶向药物；
8. 入组前，全身应用的皮质类固醇药物（强的松> 10 mg/天或等效剂量）已经停药至少2周；
9. 入组前，需要全身麻醉的大手术必须已经完成至少8 周；需要局部麻醉/硬膜外麻醉的手术必须已经完成至少4周；
10. 血常规要求血红蛋白 ≥ 90 g/L（不允许输血），中性粒细胞 ≥ 1.5 ×10^9/L（检测前14天内未使用重组人促粒细胞集落刺激因子支持治疗），血小板 ≥ 100×10^9/L（检测前7天内未使用重组人促血小板生成素或输血等支持治疗）;
11. 血清肌酐 ≤ 1.5×ULN或肌酐清除率计算值 ≥ 60 mL/min（Cockcroft-Gault公式），且尿蛋白≤2+或≤1.0 g/L。对于基线时尿蛋白≥ 2+或≥ 1.0 g/L的患者，应当进行24小时尿蛋白定量检测必须≤ 1.0 g/L方可入选；
12. 总胆红素≤1.5×ULN（除非证实患有Gilbert综合征），天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）≤ 2.5×ULN（肝转移患者允许AST和/或ALT ≤ 5 × ULN）；
13. 甲状腺功能指标：促甲状腺激素（TSH）、游离甲状腺素（FT3/FT4）在正常范围；
14. 由于既往治疗引起的不良反应在入组前恢复至1级及以下（脱发和化疗药物引起的≤2级的神经毒性除外）；
15. 给药前7天内确认未怀孕的女性，生育期男性或女性需同意在整个试验期间及试验结束后6个月内采取医学上认可的有效避孕措施；
16. 患者可以按期随访，能够与研究者作良好的沟通并能够依照研究规定完成研究。

Inclusion criteria

1. Sign the informed consent form;
2. Aged > 18 years;
3. histologically or cytologically confirmed non-small cell lung cancer, and measurable lesions according to RECIST1.1 criteria;
4. ECOG score 0-1;
5. Expected survival >= 12 weeks;
6. Include patients with driver gene (EGFR/ALK/ROS1) -negative, untreated stage II-IIIA (N2) NSCLC;
7. Patients did not receive previous anti-angiogenic small molecule targeted drugs before enrollment;
8. Systemic corticosteroids (prednisone > 10 mg/day or equivalent) have been discontinued for at least 2 weeks before enrollment;
9. Major surgery requiring general anesthesia must have been completed for at least 8 weeks; surgery requiring local anesthesia/epidural anesthesia must have been completed for at least 4 weeks;
10. Blood routine requirements: hemoglobin >= 90 g/L (no blood transfusion is allowed), neutrophils >= 1.5 x 10^9/L (14 before the test without recombinant human granulocyte colony-stimulating factor support therapy), platelets >= 100 x 10^9/L (7 before the test without recombinant human thrombopoietin or blood transfusion and other supportive therapy);
11. Serum creatinine <= 1.5 x ULN or calculated creatinine clearance >= 60 mL/min (Cockcroft-Gault formula), and urine protein <= 2 + or <= 1.0 g/L. For patients with baseline urine protein >= 2 + or >= 1.0 g/L, 24-hour urine protein quantitative test should be performed and must be <= 1.0 g/L to be included;
12. total bilirubin <= 1.5 x ULN (unless confirmed Gilbert's syndrome), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN (AST and/or ALT <= 5 x ULN are allowed for patients with liver metastases);
13. Thyroid function indicators: thyroid stimulating hormone (TSH), free thyroxine (FT3/FT4) in the normal range;
14. Adverse reactions caused by previous treatment recover to grade 1 or lower before enrollment (except alopecia and neurotoxicity <= grade 2 caused by chemotherapeutic drugs);
15. Women who are confirmed not to be pregnant within 7 days before administration, and men or women of reproductive age should agree to take medically recognized effective contraceptive measures throughout the trial and within 6 months after the end of the trial;
16. Patients can be followed up on schedule, can communicate well with the investigator and can complete the study in accordance with the study regulations.

排除标准：

1. 活动性中枢神经系统（CNS）转移，包括有症状的脑转移或脑膜转移或脊髓压迫等；无症状的脑转移可以入组（放疗后至少4周内没有进展和/或手术切除后没有出现神经症状或体征，不需要用糖皮质激素、抗癫痫药、抗惊厥药物或甘露醇治疗）；
2. 既往患有其他恶性肿瘤（已治愈的宫颈原位癌和皮肤基底细胞癌除外）的患者，不得参加研究，除非他/她在入组前完全缓解至少2年，并且不需要接受其他治疗或者研究期间不需要接受其他治疗；
3. 有活动性、已知自身免疫性疾病病史，包括但不限于系统性红斑狼疮、银屑病、类风湿性关节炎、炎性肠道疾病、桥本氏甲状腺炎等，除外：I型糖尿病、仅通过激素替代治疗可以控制的甲状腺功能减退、无需全身治疗的皮肤病（如白癜风、银屑病）和已控制的乳糜泻；
4. 以前用过抗PD-1抗体、抗PD-L1抗体、抗PD-L2抗体或抗CTLA-4 抗体治疗（或作用于T细胞协同刺激或检查点通路的任何其他抗体）；
5. 未得到控制的高血压（收缩压≥140mmHg和/或舒张压≥90mmHg）或肺动脉高压或不稳定型心绞痛；给药前6个月内有过心肌梗死或搭桥、支架手术；纽约心脏病协会（NYHA）标准3-4级的慢性心力衰竭病史；有临床意义的瓣膜病；需要治疗的严重心律失常（除外房颤、阵发性室上性心动过速），包括QTc间期男性≥450ms、女性≥470ms（以Fridericia公式计算）；给药前12个月内脑血管意外（CVA）或短暂性脑缺血发作（TIA）等；
6. 入选前6个月内有动脉血栓或深静脉血栓史，或入组前2个月内具有出血倾向证据或病史的患者，无论严重程度如何；部分凝血酶原时间（APTT）或凝血酶原时间（PT）＞1.5×ULN；
7. 皮肤伤口、手术部位、创伤部位、粘膜严重溃疡或骨折没有完全愈合；
8. 影像显示有肿瘤侵入大血管的迹象，包括肿瘤已完全接近、包绕或侵犯至大血管内腔（例如肺动脉或上腔静脉）；
9. 吞咽困难或者已知药物吸收障碍者；
10. 研究者认为会显著影响口服药物吸收的胃肠失调或可能引起消化道出血或者穿孔的状况（如十二指肠溃疡、肠梗阻、急性克罗恩病、溃疡性结肠炎、大面积胃和小肠切除等）。患有慢性克罗恩病和溃疡性结肠炎的患者（除全结肠和直肠切除者），即使在非活动期，也应排除。患有遗传性非息肉病性结直肠癌或家族性腺瘤性息肉病综合征者。既往有肠穿孔、肠瘘史，而经手术治疗后未痊愈者；
11. 现在或既往患有间质性肺炎；
12. 不能控制的需反复引流或有明显症状的胸腹腔、心包积液；
13. 需全身性治疗的活动性感染；活动性肺结核感染；
14. 丙肝抗体（HCV-Ab）、获得性免疫缺陷综合征抗体（Anti-HIV）及抗梅毒螺旋体抗体（TP-Ab）阳性；乙肝表面抗原（HBV-Ag）阳性且HBV DNA拷贝数＞检测单位正常值上限；
15. 需要用免疫抑制药物治疗的合并症，或需要按具有免疫抑制作用的剂量（强的松＞10mg/日或同类药物等效剂量）全身或局部使用皮质类固醇的合并症；
16. 开始研究药物使用前4周、治疗期间或最后一次给药5个月内预期会给予活疫苗或减毒疫苗；
17. 经询问有吸毒史或药物滥用史者；
18. 哺乳期妇女（同意在试验期间停止哺乳可以入组）；
19. 在开始使用研究药物前30天内，曾接受其它任何试验药物治疗或参加过另一项临床试验；
20. 已知对研究药物或其任何辅料成分过敏；已知有严重变态反应性疾病史；
21. 在研究期间和末次给药后的6个月期间，不使用有效避孕方法的女性；在研究期间和末次给药后的90天内，不同意使用有效避孕方法的男性；
22. 患者交流、理解和合作不够，或依从性较差，不能保证按方案要求进行者；
23. 研究者认为不适合参加本临床试验的其他情况。

Exclusion criteria：

1. Active central nervous system (CNS) metastasis, including symptomatic brain metastasis or meningeal metastasis or spinal cord compression; asymptomatic brain metastasis can be (at least 4 after radiotherapy without progression and/or no neurological symptoms or signs after surgical resection, without the need for glucocorticoids, antiepileptic drugs, anticonvulsants or mannitol treatment);
2. Patients with other previous malignancies (except cured cervical carcinoma in situ and cutaneous basal cell carcinoma) should not participate in the study, unless he/she has been in complete remission for at least 2 years before enrollment and does not require other treatment or does not require other treatment during the study;
3. A history of active, known autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., except: type I diabetes, hypothyroidism that can be controlled by hormone replacement therapy alone, skin diseases that do not require systemic treatment (such as vitiligo, psoriasis) and controlled celiac disease;
4. Previous treatment with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell costimulation or checkpoint pathway);
5. Uncontrolled hypertension (systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg) or pulmonary hypertension or unstable angina pectoris; myocardial infarction or bypass, stent surgery within 6 months before administration; New York Heart Association (NYHA) criteria grade 3-4 history of chronic heart failure; clinically significant valvular disease; severe arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia), including QTc interval >= 450 ms in men and >= 470 ms in women (calculated by Fridericia formula); cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 12 months before administration;
6. Patients with a history of arterial thrombosis or deep venous thrombosis within 6 months before enrollment, or with evidence or history of bleeding tendency within 2 months before enrollment, regardless of severity; partial prothrombin time (APTT) or prothrombin time (PT) > 1.5 x ULN;
7. Skin wounds, surgical sites, wound sites, severe mucosal ulcers or fractures are not completely healed;
8. Imaging shows signs of tumor invasion into the great vessels, including complete proximity, encasement, or invasion of the tumor into the lumen of the great vessels (e.g., pulmonary artery or superior vena cava);
9. dysphagia or known drug absorption disorder;
10. Gastrointestinal disorders that will significantly affect the absorption of oral drugs or conditions that may cause gastrointestinal bleeding or perforation (such as duodenal ulcer, intestinal obstruction, acute Crohn's disease, ulcerative colitis, massive gastric and small intestinal resection, etc.); Patients with chronic Crohn's disease and ulcerative colitis (except those with total colon and rectal resection), even in the inactive phase, should be excluded. Patients with hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis syndrome. Patients with previous history of intestinal perforation and intestinal fistula who did not recover after surgical treatment;
11. Current or previous interstitial pneumonia;
12. Uncontrolled thoracoabdominal and pericardial effusion requiring repeated drainage or with obvious symptoms;
13. Active infection requiring systemic treatment; active pulmonary tuberculosis infection;
14. Hepatitis C antibody (HCV-Ab), acquired immunodeficiency syndrome antibody (anti-HIV) and anti-treponema pallidum antibody (TP-Ab) positive; hepatitis B surface antigen (HBV-Ag) positive and HBV DNA copy number > the upper limit of normal of the detection unit;
15. Complications requiring treatment with immunosuppressive drugs, or requiring systemic or local use of corticosteroids at doses with immunosuppressive effects (prednisone > 10 mg/day or equivalent doses of the same drug);
16. Expected administration of live or attenuated vaccines 4 weeks before the start of study drug use, during treatment, or within 5 months of the last dose;
17. History of drug abuse or drug abuse upon inquiry;
18. Lactating women (agree to stop breastfeeding during the trial can be);
19. Received any other experimental drug or participated in another clinical trial within 30 days before the start of the study drug;
20. Known hypersensitivity to the study drug or any of its excipients; known history of serious allergic diseases;
21. Women who do not use effective contraceptive methods during the study and for 6 months; men who do not agree to use effective contraceptive methods during the study and for 90 days;
22. Patients with insufficient communication, understanding and cooperation, or poor compliance, can not ensure to carry out according to the requirements of the protocol;
23. Other conditions that the investigator considers inappropriate for participation in this clinical trial.

研究实施时间：

Study execute time：

从 From 2020-12-08 00:00:00至 To 2021-12-08 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2020-12-08 00:00:00 至 To 2021-12-08 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

30

Group：

experimental group

Sample size：

干预措施：

度伐利尤单抗

干预措施代码：

Intervention：

Durvalumab

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

空军特色医学中心 

单位级别：

三甲 

Institution
hospital：

Air Force Special Medical Center

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：

EFS

Type：

Primary 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

 使用后保存  

说明

Fate of sample：

Preservation 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 75 岁 years

性别：

男性

Gender：

Male

随机方法（请说明由何人用什么方法产生随机序列）：

符合入选标准的受试者被分配到度伐利尤单抗注射液联合化疗组

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

Subjects who met the inclusion criteria were assigned to the study group of Tuvalizumab Injection combined with chemotherapy.

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

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）：

http://www.chictr.org.cn/

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

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：

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)

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

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)

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-12-16 10:32:06