ChiCTR2100045112 版本V1.1 版本创建时间2021/11/02 09:51:14 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：

 ChiCTR2100045112 

最近更新日期：

Date of Last Refreshed on：

 2021-11-02 09:36:56 

注册时间：

Date of Registration：

 2021-04-07 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

替雷利珠单抗联合安罗替尼二线治疗晚期 尿路上皮癌Ⅱ期临床研究

Public title：

Tirelizumab combined with amlotinib for second-line treatment of advanced urothelial carcinoma Ⅱ Phase II clinical study

注册题目简写：

替雷利珠单抗联合安罗替尼二线治疗晚期 尿路上皮癌Ⅱ期临床研究

English Acronym：

Tirelizumab combined with amlotinib for second-line treatment of advanced urothelial carcinoma Ⅱ Phase II clinical study

研究课题的正式科学名称：

替雷利珠单抗联合安罗替尼二线治疗晚期 尿路上皮癌Ⅱ期临床研究

Scientific title：

Tirelizumab combined with amlotinib for second-line treatment of advanced urothelial carcinoma Ⅱ Phase II 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：

朴龙镇 

研究负责人：

朴龙镇 

Applicant：

Piao Longzhen 

Study leader：

Piao Longzhen 

申请注册联系人电话：

Applicant telephone：

 15526771162

研究负责人电话：

Study leader's
telephone：

+86-15526771162

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：

 plz1978@126.com

研究负责人电子邮件：

Study leader's E-mail：

 plz1978@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：

吉林省延吉市局子街1327号

研究负责人通讯地址：

吉林省延吉市局子街1327号

Applicant address：

1327 Juzi Street, Yanji City, Jilin Province, China

Study leader's address：

1327 Juzi Street, Yanji City, Jilin Province, 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：

延边大学附属医院

Applicant's institution：

Yanbian University Hospital

研究负责人所在单位：

延边大学附属医院

Affiliation of the Leader：

Yanbian University 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：

 延边伦理2021005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：

延边大学附属医院伦理委员会

Name of the ethic committee：

Yanbian University Hospital Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

 2021-03-24 00:00:00

伦理委员会联系人：

李金花

Contact Name of the ethic committee：

Li Jinhua

伦理委员会联系地址：

吉林省延吉市局子街1327号延边大学附属医院行政楼310

Contact Address of the ethic committee：

Room 310, Administrative Building, Yanbian University Hospital, No. 1327, Juzi Street, Yanji City, Jilin Province，China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 0433-2669880

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 yanbianyiyuanlunli@163.com

研究实施负责（组长）单位：

延边大学附属医院

Primary sponsor：

Yanbian University Hospital

研究实施负责（组长）单位地址：

吉林省延吉市局子街1327号

Primary sponsor's address：

1327 Juzi Street, Yanji City, Jilin Province, 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)：

吉林

市(区县)：

延吉

Country：

China

Province：

Jilin

City：

Yanji

单位(医院)：

延边大学附属医院

具体地址：

局子街1327号

Institution
hospital：

Yanbian University Hospital

Address：

1327 Juzi Street

经费或物资来源：

自筹

Source(s) of funding：

self-raised

研究疾病：

尿路上皮癌  

Target disease：

Urothelial carcinoma

研究疾病代码：

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：

评价注射用替雷利珠单抗联合安罗替尼二线治疗晚期尿路上皮癌初步疗效和安全性。  

Objectives of Study：

To evaluate the primary efficacy and safety of tirelizumab for injection combined with amlotinib in the second-line treatment of advanced urothelial carcinoma.

药物成份或治疗方案详述：

盐酸安罗替尼胶囊，10mg/天，早餐前口服，QD，连续服药2周停药1周。 替雷利珠单抗注射液，200 mg，静脉滴注给药（无需预防用药），每次输注30 min（不少于20 min，不超过60 min），Q3W，每3周（21天）为一个周期。尽量在ECG检查之前完成给药。 两药从第一天开始同时给药，直至疾病进展或因不可耐受而终止。 盐酸安罗替尼胶囊剂量调整：研究过程中，受试者因药物相关的不良事件可下调盐酸安罗替尼剂量至8 mg，若8 mg 剂量水平下无法耐受的受试者需终止研究。对于盐酸安罗替尼胶囊经下调剂量至 8 mg 的受试者，用药一段时间后，若研究者判定疾病存在进展可能，但仍有通过上调剂量使受试者受益，受试者安全性稳定后，则可上调剂量 1 次。每例受试者最多只能进行 1 次剂量上调，且不能跨剂量组调整。 替雷利珠单抗注射液不允许进行剂量调整，出现不能继续用药的不良反应经研究者判断给予停药处理。 

Description for medicine or protocol of treatment in detail：

Anlotinib hydrochloride capsule, 10mg/ day, taken orally before breakfast, QD, continuous medication for 2 weeks, stopped for 1 week. Tirellizumab injection, 200 mg, was given intravenously (without prophylactic medication), each infusion for 30 min (no less than 20 min, no more than 60 min), q3W, every 3 weeks (21 days) as a cycle. Try to complete the administration before the ECG examination. Both drugs are given together from the first day until the disease progresses or is discontinued due to intolerance. Dose adjustment of amrotinib hydrochloride capsules: During the study, the dose of amrotinib hydrochloride can be reduced to 8 mg due to drug-related adverse events. If the patient cannot tolerate the dose at 8 mg, the study should be terminated. For subjects whose amrottinib hydrochloride capsule was down-regulated to 8 mg, the dose can be upregulated once after a period of time, if the investigator determines that disease progression is possible, but the upregulated dose still benefits the subjects, and the subjects are safe and stable. Dose upregulation is limited to 1 dose per subject and cannot be adjusted across dose groups. The dose of tirelizumab injection was not allowed to be adjusted, and adverse reactions that could not be continued were judged by the researcher to be discontinued. 

纳入标准：

患者必须满足以下所有入选标准才可入组本研究：
1.患者自愿加入本研究，签署知情同意书；
2.≥18岁，男女皆可；
3.经过病理学或细胞学确诊为晚期尿路上皮癌的患者（可参考首次病理结果）；
4.既往经一线化疗治疗后疾病进展；
5.根据RECIST 1.1版，必须至少有一个可测量的病灶；
6.ECOG评分：0-1分；
7.预期生存期≥12周；
8.主要器官功能符合下列要求（在开始研究治疗前7天内）：
（1）血常规检查：（除外血红蛋白，筛查前14天内未输血、未使用粒细胞集落刺激因子 [G-CSF]、未使用药物纠正）：
?中性粒细胞绝对计数≥1.5×109/L；
?血小板≥75×109/L；
?血红蛋白≥90 g/L；
（2）生化检查：（筛查前14天内未输白蛋白）：
?血清白蛋白≥29 g/L；
?血清总胆红素≤1.5×正常范围上限（ULN）；
?丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）和碱性磷酸酶（AKP）≤5×ULN；
?血清肌酐（Cr）≤1.5ULN或Cr清除率>50 mL/min（Cockcroft-Gault公式如下）
男性：Cr清除率=((140-年龄)×体重)/(72×血Cr)
女性：Cr清除率=((140-年龄)×体重)/(72×血Cr) × 0.85
体重单位：kg；血Cr单位：mg/mL；
（3）国际标准化比率（INR）≤2.3或凝血酶原时间（PT）超过正常对照的范围≤6秒；
（4）尿蛋白<2+（若尿蛋白≥2+，可以进行24小时（h）尿蛋白定量，24h尿蛋白定量<1.0 g可以入组）
9.有生育能力的女性：必须同意从签署知情同意书开始直到研究药物末次给药后至少120天内禁欲（避免异性性交）或使用可靠、有效方法避孕。且在开始研究治疗前的7天内血清HCG检查必须为阴性；而且必须为非哺乳期。
如果女性患者已来月经、尚未达到绝经后状态（连续无月经时间≥12个月，除绝经之外未发现其他原因），且未接受过绝育手术（如子宫切除术、双侧输卵管结扎术或双侧卵巢切除术），则认为该患者有生育能力。
对于伴侣为育龄妇女的男性患者，必须同意从签署知情同意书开始直到研究药物末次给药后至少120天内禁欲，或使用可靠、有效方法避孕。在同一时间段内男性受试者也必须同意不捐精子。伴侣已怀孕的男性受试者须使用避孕套，无须再采用其它避孕方法。

Inclusion criteria

To be included in the study, patients must meet all of the following inclusion criteria:

1. Patients voluntarily participated in the study and signed the informed consent;

2. Male and female aged 18 or above;

3. Patients diagnosed with advanced urothelial carcinoma by pathology or cytology (refer to the first pathological results);

4. Disease progression after previous first-line chemotherapy;

5. According to RECIST version 1.1, there must be at least one measurable lesion;

6.ECOG score: 0-1;

7. Expected survival ≥12 weeks;

8. Major organ function meets the following requirements (within 7 days prior to initiation of study treatment) :

(1) Routine blood examination: (except hemoglobin, no blood transfusion, no use of granulocyte colony stimulating factor [G-CSF], no use of drug correction within 14 days before screening) :

? Absolute neutrophils count ≥1.5×109/L;

? Platelet ≥75×109/L;

? Hemoglobin ≥90 g/L;

(2) Biochemical examination: (no albumin infusion within 14 days before screening) :

? Serum albumin ≥29 g/L;

? Serum total bilirubin ≤1.5× upper normal range (ULN);

? Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP) ≤5×ULN;

? Serum creatinine (Cr) ≤1.5ULN or Cr clearance >50 mL/min (Cockcroft-Gault formula follows)

Male: CR clearance =((140- age)× weight)/(72× blood CR)

Female: CR clearance rate =((140- age)× weight)/(72× blood CR)× 0.85

Weight unit: Kg; Blood Cr unit: mg/mL;

(3) International standardized ratio (INR) ≤2.3 or prothrombin time (PT) exceeds the range of normal control ≤6 seconds;

(4) Urine protein <2+ (if urine protein ≥2+, 24-hour (h) urine protein quantification can be performed, and 24h urine protein quantification < 1.0g can be included)

9. Fertile women: must agree to abstain from sex (avoiding heterosexual intercourse) or use a reliable, effective method of contraception for at least 120 days from the date of signing the informed consent form until the last dose of the study drug. Serum HCG tests must be negative within 7 days prior to the start of study treatment; And it must be non-lactation.

A female patient is considered to be fertile if she is menstruating and has not yet reached postmenopausal status (continuous absence of menstrual duration ≥12 months, no cause other than menopause found) and has not undergone sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).

For male patients whose partner is a woman of childbearing age, they must agree to abstain from sex or use a reliable, effective method of contraception for at least 120 days from the date of signing an informed consent until the last dint of the study drug. Male subjects also had to agree not to donate sperm during the same period. Male subjects whose partners are pregnant should use condoms and no other method of contraception is required.

排除标准：

患者若符合以下任何一种情况，将不得进入本研究：
1.准备进行或者既往接受过器官或同种异基因骨髓移植的患者；
2.通过事先筛查和影像学评估发现具有活动性脑转移的患者；
3.研究治疗开始前6个月内有消化道出血病史或具有明确的胃肠道出血倾向，如：有出血危险的或重度食管胃底静脉曲张、有局部活动性消化道溃疡病灶、持续大便潜血阳性不可入组（基线期若大便潜血阳性，可复查，复查后若仍为阳性，需要进行胃十二指肠镜检（EGD），若EGD提示出血风险的食管胃底静脉曲张则不能入组）；
4.研究治疗开始前6个月内出现过腹部瘘管、胃肠道穿孔或腹腔脓肿；
5.已知存在的遗传性或获得性出血（如凝血功能障碍）或血栓倾向，如血友病病人；目前正在或近期（研究治疗开始前10天内）曾出于治疗目的使用全剂量口服或注射抗凝药物或溶栓药物（允许预防性使用小剂量阿司匹林、低分子肝素）；
6.目前正在使用或近期曾使用（研究治疗开始前10天内）阿司匹林（> 325 mg/天(最大抗血小板剂量）或双嘧达莫、噻氯匹定、氯吡格雷和西洛他唑治疗；
7.研究治疗开始前6个月内发生过血栓形成或栓塞事件，例如脑血管意外（包括短暂性脑缺血发作、脑出血、脑梗塞）、肺栓塞等；
8.有未能良好控制的心脏临床症状或疾病，如：（1）按照纽约心脏病协会（NYHA）标准（见附件5）II级以上心脏功能不全或心脏彩超检查：LVEF（左室射血分数）<50%；（2）不稳定型心绞痛；（3）研究治疗开始前1年内发生过心肌梗死；（4）有临床意义的室上性或室性心律失常需要治疗或干预；（5）QTc > 450ms（男性）；QTc > 470ms （女性）（QTc间期以Fridericia公式计算；若QTc异常，可间隔2分钟连续检测三次，取其平均值）；
9.患有高血压，且经降压药物治疗无法获得良好控制（收缩压≥140 mmHg或者舒张压≥90 mmHg）（基于≥2次测量获得的BP读数的平均值），允许通过使用降压治疗实现上述参数；既往曾出现高血压危象或高血压性脑病；
10.在研究治疗开始前6个月内出现重大血管疾病（例如，需要手术修补或近期有外周动脉血栓形成的主动脉瘤）；
11.严重、未愈合或裂开的伤口以及活动期溃疡或未经治疗的骨折；
12.在研究治疗开始前4周内接受过大手术治疗（诊断除外）或预期需在研究期间进行大手术治疗；
13.不能吞咽药片的状况；
14.在开始研究治疗之前6个月内曾患肠梗阻和/或曾有胃肠道梗阻临床体征或症状，包括与原有疾病有关或需要常规肠外水化、肠外营养或管饲的不完全梗阻：
在初始诊断时如果有不完全梗阻/梗阻综合征/肠梗阻体征/症状的患者接受了明确（外科）治疗以消退症状时，患者或许可入组研究；
15.有证据表明存在无法通过穿刺或近期外科手术解释说明的腹内积气；
16.既往或目前存在中枢神经系统转移；
17.涉及主要气道或血管的转移性疾病（比如由于肿瘤侵犯导致完全闭塞的门静脉主干或腔静脉需要排除入组，门静脉主干是指脾静脉和肠系膜上静脉的汇合处以及肝门静脉分为左右支的分支处）或位于中心的大体积纵隔肿瘤块（距隆嵴<30 mm）；
18.目前伴有间质性肺炎或间质性肺病，或既往有需激素治疗的间质性肺炎或间质性肺病病史者，或其他可能干扰免疫相关肺毒性判断和处理的肺纤维化、机化性肺炎（例如，闭塞性细支气管炎）、尘肺、药物相关肺炎、特发性肺炎或在筛选期胸部计算机断层扫描（CT）图上可见活动性肺炎证据或肺功能严重受损的受试者，允许放射野曾有辐射性肺炎；活动性结核；
19.存在活动性自身免疫病或有自身免疫病病史且可能复发（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、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]）；受试者患有无需系统治疗的皮肤病如白癜风、银屑病、脱发，接受胰岛素治疗的经控制的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；
20.在开始研究治疗之前14天内使用免疫抑制剂或全身激素治疗以达到免疫抑制目的（剂量>10mg/天泼尼松或其他等疗效激素）；
21.在开始研究治疗之前14天内使用强CYP3A4/ CYP2C19诱导剂包括利福平（及其类似物）和贯叶连翘或强CYP3A4/ CYP2C19抑制剂；
22.已知对任何单克隆抗体、抗血管生成靶向药物有严重过敏史；
23.在开始研究治疗之前4周内有重度感染，包括但不限于因感染、菌血症或重度肺炎并发症而住院治疗；在开始研究治疗之前2周内口服或静脉给予治疗性抗生素（接受预防性抗生素（例如，预防尿路感染或慢性阻塞性肺病加重的患者有资格参与研究）；
24.患者先天或后天免疫功能缺陷（如HIV感染者）；
25.乙肝表面抗原（HBsAg） 阳性且乙型肝炎病毒 DNA 拷贝数≥2000 IU/mL（HBsAg 阳性且乙型肝炎病毒 DNA 拷贝数<2000 IU/mL者需至少接受 2 周抗 HBV 治疗才能首次给药）；丙型肝炎病毒（HCV）抗体阳性且 HCV RNA 检测阳性。
26.既往曾接受过其他抗PD-1抗体治疗或其他针对PD-1/PD-L1的免疫治疗，或既往接受过抗血管生成药物治疗；
27.在开始研究治疗之前28天内接受过减毒活疫苗治疗，或预期于参与本研究治疗期间或参与本研究末次给药后60天内需要接种此类疫苗；
28.在开始研究治疗之前28天内接受过其他试验用药物治疗；
经研究者判断，患者有其他可能影响研究结果或导致本研究被迫中途终止的因素，如酗酒、药物滥用、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，会影响到患者的安全。

Exclusion criteria：

Patients who meet any of the following conditions will not be admitted to the study:

1. Patients who are preparing for or have previously received an organ or allogeneic bone marrow transplant;

2. Patients with active brain metastases identified by pre-screening and imaging evaluation;

3. The research and treatment within 6 months prior to the start of a history of gastrointestinal bleeding or a gastrointestinal bleeding tendency, such as: there is a risk of hemorrhage or severe esophageal gastric varices, any local activity of the digestive tract ulcer lesions and continuous defecate occult blood positive shall not enter into the group (baseline period if defecate occult blood positive, can review, after review if still positive, gastroduodenal microscopy (or EGD) is required, if or EGD hint of esophageal gastric varices bleeding risk is not into the group);

4. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 6 months prior to study treatment;

5. Known hereditary or acquired bleeding (e.g., coagulation dysfunction) or thrombotic tendencies, such as hemophilia; Is currently or recently (within 10 days prior to the commencement of study treatment) using a full dose of an oral or injected anticoagulant or thrombolytic drug for therapeutic purposes (allowing prophylactic use of low-dose aspirin, low-molecular weight heparin);

6. Current use or recent use (within 10 days prior to study treatment initiation) of aspirin (> 325 mg/ day (maximum anti-platelet dose) or dipyridamole, ticlopidine, clopidogrel, and cilotazole;

7. Thrombosis or embolism events, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc., occurred within 6 months before the study treatment;

8. Have not well controlled cardiac clinical symptoms or diseases, such as: (1) according to the New York Heart Association (NYHA) standards (see Annex 5) class II or above cardiac dysfunction or cardiac color ultrasound examination: LVEF (left ventricular ejection fraction) <50%; (2) unstable angina pectoris; (3) Myocardial infarction occurred within 1 year prior to study treatment; (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) QTC > 450ms (male); QTc > 470ms (female) (QTc interval calculated by Fridericia formula; If QTC is abnormal, it can be detected continuously for three times at an interval of 2 minutes, and the average value is taken);

9. Have hypertension that is not well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) (based on the mean of BP readings from ≥2 measurements) and are allowed to use antihypertensive therapy to achieve the above parameters; Previous hypertensive crisis or hypertensive encephalopathy;

10. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral artery thrombosis) occurred within 6 months prior to study treatment initiation;

11. Severe, unhealed or open wounds and active ulcers or untreated fractures;

12. Underwent major surgery (other than diagnosis) within 4 weeks prior to the start of study treatment or was expected to undergo major surgery during the study period;

13. Inability to swallow pills;

14. A history of intestinal obstruction and/or clinical signs or symptoms of gastrointestinal obstruction within 6 months prior to the commencement of study treatment, including incomplete obstruction related to the pre-existing disease or requiring routine parenteral hydration, parenteral nutrition or tube feeding:

Patients with incomplete obstruction/obstruction syndrome/ileus signs/symptoms at the time of initial diagnosis may be enrolled if they receive specific (surgical) treatment to subside the symptoms;

15. Evidence of intra-abdominal gas that cannot be explained by puncture or recent surgical procedures;

16. Previous or current central nervous system metastases;

17. Involving the main resistance, or the transfer of vascular disease (such as due to tumor invasion of the occlusion of portal vein trunk or vena cava need to rule out into groups, portal venous trunk is refers to the stands at the junction of splenic vein and superior mesenteric vein and hepatic vein can be divided into left and right sides of the branch) or block is located in the center of mass mediastinal tumors (from long ridge < 30 mm);

18. Currently associated with interstitial pneumonia or interstitial lung disease, or has a need to hormone treatment of interstitial pneumonia or history of interstitial lung disease, or other related lung toxicity may interfere with the immune judgment and treatment of pulmonary fibrosis, machine pneumonia (for example, occlusive bronchiolitis), pneumoconiosis, drug related pneumonia, idiopathic pneumonia or phase in the screening of the chest computed tomography (CT) is visible on the map active pneumonia evidence or severely damaged lung function were allowed to radiation field had radiation pneumonia; Active tuberculosis;

19. There is active autoimmune disease or a history of autoimmune disease and may recur (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, 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 conditions such as vitiligo, psoriasis, alopecia, controlled type I diabetes on insulin therapy, or complete remission of asthma in childhood without any intervention as adults were included; Patients with asthma requiring bronchodilators for medical intervention were not included;

20. Immunosuppressant or systemic hormone therapy for immunosuppressive purposes within 14 days prior to initiation of study therapy (dose of >10mg/ day prednisone or other equivalent therapeutic hormone);

21. Use of a strong CYP3A4/ CYP2C19 inducer including rifampine (and its analogues) and Hypericum perforatum or a strong CYP3A4/ CYP2C19 inhibitor within 14 days prior to initiation of study therapy;

22. Has a known history of severe allergy to any monoclonal antibody or anti-angiogenic targeting drug;

23. Severe infection, including but not limited to hospitalization due to complications of infection, bacteremia, or severe pneumonia, occurred 4 weeks prior to the initiation of study treatment; Therapeutic antibiotics were given orally or intravenously within 2 weeks prior to the initiation of study treatment (patients receiving prophylactic antibiotics (for example, patients who were eligible to participate in the study for prevention of urinary tract infections or exacerbations of chronic obstructive pulmonary disease);

24. Patients with congenital or acquired immune deficiency (such as HIV infection);

25. Hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number ≥2000 IU/mL (HBsAg positive with HBV DNA copy number <2000 IU/mL should receive at least 2 weeks of anti-HBV therapy before first administration); Hepatitis C virus (HCV) antibody was positive and HCV RNA was positive.

26. Previous experience with other anti-PD-1 antibody therapy or other PD-1/PD-L1 immunotherapy, or previous anti-angiogenic drug therapy;

27. Has received live attenuated vaccine within 28 days prior to the commencement of study treatment, or is expected to receive such vaccine during the study treatment period or within 60 days after the last administration of study;

28. Received other investigational drug treatment within 28 days prior to initiation of study treatment;

According to the researcher's judgment, the patients have other factors that may affect the results of the study or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment, severe laboratory examination abnormalities, accompanied by family or social factors, which will affect the safety of patients.

研究实施时间：

Study execute time：

从 From 2021-04-01 00:00:00至 To 2024-04-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2021-04-01 00:00:00 至 To 2024-04-01 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 48

Group：

Experimental group

Sample size：

干预措施：

替雷利珠单抗联合安罗替尼给药

干预措施代码：

Intervention：

Tilelizumab combined with Anlotinib

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 吉林 

市(区县)：

 延吉 

Country：

China

Province：

Jilin

City：

Yanji

单位(医院)：

 延边大学附属医院 

单位级别：

 三级甲等 

Institution
hospital：

Yanbian University Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

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：

无疾病进展生存期

指标类型：

主要指标

Outcome：

Disease-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：

缓解持续时间

指标类型：

主要指标

Outcome：

Duration of relief

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：

主要指标

Outcome：

Disease control 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：

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：

安全性

指标类型：

主要指标

Outcome：

Safety

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 100 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）：

不适用

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

NA

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）：

http://www.yanbianhospital.com/

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

http://www.yanbianhospital.com/

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：

  2021-04-07 04:02:37