ChiCTR2100049108 版本V1.0 版本创建时间2022/02/24 11:43:37 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：

 ChiCTR2100049108 

最近更新日期：

Date of Last Refreshed on：

 2021-07-21 02:49:31 

注册时间：

Date of Registration：

 2021-07-21 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。 卡瑞利珠单抗联合GC方案新辅助治疗 局部晚期膀胱癌的探索性临床研究

Public title：

Exploratory clinical study of carrelizumab combined with GC regimen in neoadjuvant treatment of locally advanced bladder cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

卡瑞利珠单抗联合GC方案新辅助治疗 局部晚期膀胱癌的探索性临床研究

Scientific title：

Exploratory clinical study of carrelizumab combined with GC regimen in neoadjuvant treatment of locally advanced bladder 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：

李杨 

研究负责人：

李鑫 

Applicant：

LiYang 

Study leader：

LiXin 

申请注册联系人电话：

Applicant telephone：

 18347254960

研究负责人电话：

Study leader's
telephone：

15047200015

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：

 18347254960@163.com

研究负责人电子邮件：

Study leader's E-mail：

 592676401@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：

内蒙古包头市青山区翡丽湾5栋

研究负责人通讯地址：

内蒙古包头市青山区团结大街包头市肿瘤医院

Applicant address：

Building 5, Feiliwan, Qingshan District, Baotou City, Inner Mongolia

Study leader's address：

Baotou Cancer Hospital, Tuanjie Street, Qingshan District, Baotou, Inner Mongolia

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：

江苏恒瑞医药股份有限公司

Applicant's institution：

Jiangsu Hengrui Pharmaceutical Co., Ltd.

研究负责人所在单位：

Affiliation of the Leader：

是否获伦理委员会批准：

否

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：

包头市肿瘤医院

Primary sponsor：

Baotou Cancer Hospital

研究实施负责（组长）单位地址：

内蒙古包头市青山区团结大街18号

Primary sponsor's address：

18 Tuanjie Street, Qingshan District, Baotou City, Inner Mongolia

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

内蒙古自治区

市(区县)：

包头

Country：

China

Province：

Inner Mongolia Autonomous Region

City：

Baotou

单位(医院)：

包头市肿瘤医院

具体地址：

青山区团结大街18号

Institution
hospital：

Baotou Cancer Hospital

Address：

18 Tuanjie Street, Qingshan District

经费或物资来源：

经费自筹

Source(s) of funding：

Self-funded

研究疾病：

尿路上皮癌  

Target disease：

Bladder 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：

单臂 

Study design：

Single arm 

研究目的：

主要研究目的： 评价卡瑞利珠单抗联合GC方案新辅助治疗局部晚期膀胱癌的有效性 次要研究目的： 1. 评价卡瑞利珠单抗联合GC方案术前新辅助治疗局部晚期膀胱癌的安全性、耐受性 2. 评价卡瑞利珠单抗联合GC方案术前新辅助治疗相关不良事件发生率（时限：最长1年） 3. 评价手术治疗相关延迟事件的发生率 4. 客观的缓解率（ORR）、疾病控制率（DCR）、无病生存期（DFS）、总生存期（OS）及12个月生存率 5. 生活质量评估表  

Objectives of Study：

Main research purposes: To evaluate the effectiveness of carrelizumab combined with GC regimen in neoadjuvant treatment of locally advanced bladder cancer Secondary research purpose: 1. To evaluate the safety and tolerability of carrelizumab combined with GC regimen in preoperative neoadjuvant treatment of locally advanced bladder cancer 2. To evaluate the incidence of adverse events related to carrelizumab combined with GC regimen before neoadjuvant therapy (time limit: up to 1 year) 3. Evaluate the incidence of delayed events related to surgical treatment 4. ORR, DCR, DFS OS and 12-month survival rate 5. Quality of Life Assessment Form

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；
2.预期生存期≥3个月；
3.东部肿瘤协作组（ECOG）体力状态评分必须为0-1分；
4.至少有一个符合RECISTv1.1标准的可测量病灶（根据RECISTv1.1要求该可测量病灶螺旋CT扫描长径≥10mm或肿大淋巴结短径≥15mm）；
5.组织病理学证实的局部晚期膀胱尿路上皮癌，无转移病灶证据，混合型癌要求主要的组织学类型为尿路上皮癌亚型；
6.既往未经过含铂类方案的化疗；
7.临床诊断为局部晚期膀胱癌患者，可伴有或不伴有盆腔淋巴结肿大（cT2-T4a，N0-1，M0）；
8.适合并计划进行根治性膀胱切除术（根据指南）；
9.在第一次研究治疗前4周内有足够的血液学和终末器官功能，定义如下：
·具有足够的骨髓储备和器官功能
1)嗜中性粒细胞计数（ANC）≥1500/mm3（在第1周期，第1天之前2周内没有粒细胞集落刺激因子支持）；
2)白细胞计数（WBC）>2500/μL；
3)淋巴细胞计数≥500/μL；
4)血小板计数（PLT）≥100,000/mm3（在第1周期，第1天之前2周内未输血）；
5)血红蛋白（Hb）≥9 g/dL（患者可以输血或接受红细胞生成治疗以满足此标准）；
6)血清肌酐（Cr）≤1.5倍正常值上限（ULN）或内生肌酐清除率≥60mL/min（Cockcroft-Gault公式）；
7)总胆红素（BIL）≤1.5倍正常值上限（ULN）；
8)谷草转氨酶（AST/SGOT）或谷丙转氨酶（ALT/SGPT）水平≤2.5倍正常值上限（ULN）（已知吉尔伯特病患者，其血清胆红素水平≤3×机构ULN可参加）；
9)国际标准化比值（INR）≤1.5，凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）≤1.5倍ULN（这仅适用于未接受治疗性抗凝治疗的患者; 接受治疗性抗凝治疗的患者应服用稳定的剂量）；
10.女性应同意在研究期间和研究结束后6个月内必须采用避孕措施（如宫内节育器[IUD]，避孕药或避孕套）；在研究入组前的7天内血清或尿妊娠试验阴性，且必须为非哺乳期患者；男性应同意在研究期间和研究期结束后6个月内必须采用避孕措施的患者；
受试者愿意并理解、签署知情同意书，能够遵守协议。

Inclusion criteria

1. Age ≥ 18 years old;
2. Expected survival period ≥ 3 months;
3. The Eastern Cooperative Oncology Group (ECOG) physical status score must be 0-1 points;
4. There is at least one measurable lesion that meets the RECISTv1.1 standard (according to the requirements of RECISTv1.1, the long diameter of the spiral CT scan of the measurable lesion is ≥10mm or the short diameter of enlarged lymph nodes is ≥15mm);
5. Locally advanced bladder urothelial carcinoma confirmed by histopathology, no evidence of metastatic lesions, mixed type cancer requires that the main histological type is urothelial carcinoma subtype;
6. Have not undergone chemotherapy with platinum-based regimens in the past;
7. Clinically diagnosed as locally advanced bladder cancer patients, with or without pelvic lymphadenopathy (cT2-T4a, N0-1, M0);
8. Appropriate and plan for radical cystectomy (according to the guidelines);
9. Sufficient hematology and end-organ function within 4 weeks before the first study treatment, defined as follows:
·Have sufficient bone marrow reserve and organ function
1) Neutrophil count (ANC) ≥1500/mm3 (in the first cycle, there is no granulocyte colony stimulating factor support within 2 weeks before the first day);
2) White blood cell count (WBC)>2500/μL;
3) Lymphocyte count ≥500/μL;
4) Platelet count (PLT) ≥100,000/mm3 (in cycle 1, no blood transfusion within 2 weeks before day 1);
5) Hemoglobin (Hb) ≥9 g/dL (patients can receive blood transfusion or receive erythropoiesis therapy to meet this standard);
6) Serum creatinine (Cr) ≤ 1.5 times the upper limit of normal (ULN) or endogenous creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula);
7) Total bilirubin (BIL) ≤ 1.5 times the upper limit of normal (ULN);
8) Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) level ≤2.5 times the upper limit of normal (ULN) (Patients with Gilberts disease are known to have serum bilirubin levels ≤3×ULN of institutions can participate );
9) International normalized ratio (INR) ≤ 1.5, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN (this is only applicable to patients who have not received therapeutic anticoagulation therapy; receiving therapeutic Patients on anticoagulant therapy should take a stable dose);
10. Women should agree to use contraceptive measures (such as intrauterine device [IUD], contraceptives or condoms) during the study period and within 6 months after the end of the study; serum or urine pregnancy test within 7 days before study entry Negative, and must be a non-lactating patient; men should agree to use contraceptive measures during the study period and within 6 months after the end of the study period;
The subjects are willing, understand and sign the informed consent form, and are able to abide by the agreement.

排除标准：

1.患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；患者患有白癜风；在童年期哮喘已完全缓解，成人后无需任何干预的可纳入；患者需要支气管扩张剂进行医学干预的哮喘则不能纳入）；
2.患者正在使用免疫抑制剂、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），并在首次给药前2周内仍在继续使用的；
3.对其他单克隆抗体发生过重度过敏反应；
4.受试者有未经治疗的中枢神经系统转移，既往接受过系统性、根治性脑或脑膜转移治疗（放疗或手术），如影像学证实稳 定已维持至少1个月，且已停止全身性激素治疗（剂量>10mg/天泼尼松或其他等疗效激素）大于2周、无临床证状的患者可以纳入；
5.患有高血压，且经降压药物治疗无法获得良好控制（收缩压≥140mmHg或者舒张压≥90mmHg）；
6.有未能良好控制的心脏临床症状或疾病，如：1）NYHA2 级以上心力衰竭；2）不稳定型心绞痛；3）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)；6）排除心脏射血分数EF＞50%。
7.凝血功能异常（INR>2.0、PT>16s），具有出血倾向或正在接受溶栓或抗凝治疗，允许预防性使用小剂量阿司匹林、低分子肝素；
8.首次给药前4周内发生任何严重分级达到CTCAE 5.0中2度或以上的出血事件；
9.影像学显示肿瘤已侵犯重要血管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；
10.首次给药前6个月内发生的动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作、脑出血、脑梗塞）、深静脉血栓及肺栓塞等；
11.先前接受化疗（含铂类化疗）、手术，在治疗完成后(末次用药)，研究用药前不足4周的患者；姑息性放疗后不足2周者；分子靶向治疗（包括其他临床试验用口服靶向药）距首次研究用药＜5个药物半衰期，或先前治疗引起的不良事件（脱发除外）未恢复至≤CTCAE 1级的患者；
12.研究用药前12个月内接受过盆腔放疗后引起放射性肠炎的患者；
13.患有活动性感染、用药前7天内有不明原因发热≥38.5℃、或基线期白细胞计数>15×109/L；
14.已知有间质性肺病或存在接受了皮质类固醇激素治疗的非感染性肺炎病史或证据；或可能会干扰可疑的药物相关肺毒性的检测或处理的患者；
15.有免疫缺陷病史，包括人类免疫缺陷病毒（HIV）血清检查阳性，或患有其他获得性、先天性免疫缺陷疾病，及已知受试者处于结核病活动期；
16.已知乙型肝炎病毒（HBV）或者丙型肝炎病毒（HCV）感染活动期（乙肝参考：HBsAg阳性且HBVDNA≥500IU/ml；丙肝参考：HCV抗体阳性且HCV病毒拷贝数>正常值上限）；
17.患者既往5年内或同时患有其它恶性肿瘤（已治愈的皮肤基底细胞癌和宫颈原位癌除外；针对既往合并乳腺癌的复发性卵巢癌患者，乳腺癌根治术后>3年无复发者除外）；
18.既往接受过PD-1单、PD-L1单抗、CTLA-4单抗（或作用于T细胞协同刺激或检查点通路的任何其他抗体）治疗；
19.首次给药前4周内或可能于研究期间接种活疫苗；
20.拒绝接受新辅助顺铂化疗或以新辅助顺铂为基础的治疗不适合的患者；
21.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。
22.妊娠或哺乳的女性患者；
研究者判断其他可能影响临床研究进行、可能无法遵守协议的患者或不能配合者、存在研究风险的患者。

Exclusion criteria：

1. The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis , Hyperthyroidism; patients suffering from vitiligo; asthma has been completely relieved in childhood, and can be included in adults without any intervention; patients with asthma that require bronchodilators for medical intervention cannot be included);
2. The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before the first administration;
3. Severe allergic reaction to other monoclonal antibodies;
4. The subject has untreated central nervous system metastasis, and has previously received systemic, radical brain or meningeal metastasis therapy (radiotherapy or surgery), if imaging confirmed that the stability has been maintained for at least 1 month, and the whole body has been stopped Patients with sex hormone therapy (dose>10mg/day prednisone or other curative hormones) for more than 2 weeks without clinical symptoms can be included;
5. Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
6. There are clinical symptoms or diseases of the heart that are not well controlled, such as: 1) Heart failure above NYHA level 2; 2) Unstable angina; 3) Myocardial infarction occurred within 1 year; 4) Supraventricular or clinically significant Ventricular arrhythmia requires treatment or intervention; 5) QTc>450ms (male); QTc>470ms (female); 6) Exclude cardiac ejection fraction EF>50%.
7. Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin;
8. Any bleeding event with a severity level of CTCAE 5.0 of 2 or more occurred within 4 weeks before the first administration;
9. Imaging shows that the tumor has invaded important blood vessels or the researcher has judged that the patient's tumor is highly likely to invade important blood vessels and cause fatal bleeding during treatment;
10. Arterial/venous thrombosis events that occurred within 6 months before the first administration, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
11. Patients who have previously received chemotherapy (including platinum-based chemotherapy), surgery, after the completion of the treatment (last medication), and less than 4 weeks before the study medication; less than 2 weeks after palliative radiotherapy; molecular targeted therapy (including other clinical trials) Oral targeted drugs) are less than 5 drug half-lives from the first study drug, or the adverse events caused by previous treatment (except for alopecia) have not recovered to ≤ CTCAE level 1;
12. Patients with radiation enteritis after receiving pelvic radiotherapy within 12 months before the study medication;
13. Suffer from active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count >15×109/L;
14. Patients who are known to have interstitial lung disease or have a history or evidence of non-infectious pneumonia treated with corticosteroids; or may interfere with the detection or treatment of suspected drug-related pulmonary toxicity;
15. A history of immunodeficiency, including human immunodeficiency virus (HIV) sero-positive, or suffering from other acquired or congenital immunodeficiency diseases, and the subject is known to be in the active stage of tuberculosis;
16. Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection active period (hepatitis B reference: HBsAg positive and HBVDNA≥500IU/ml; hepatitis C reference: HCV antibody positive and HCV virus copy number> upper limit of normal value );
17. The patient has suffered from other malignant tumors in the past 5 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ; for patients with recurrent ovarian cancer with previous breast cancer, no recurrence> 3 years after radical mastectomy Except those);
18. Previously received PD-1 monoclonal antibody, PD-L1 monoclonal antibody, CTLA-4 monoclonal antibody (or any other antibody that acts on T cell co-stimulation or checkpoint pathway) treatment;
19. Live vaccines may be vaccinated within 4 weeks before the first administration or possibly during the study period;
20. Patients who refuse to accept neoadjuvant cisplatin chemotherapy or neoadjuvant cisplatin-based treatment is not suitable;
21. According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, and serious laboratory tests. Abnormalities, accompanied by family or social factors, will affect the safety of patients.
22. Female patients who are pregnant or breastfeeding;
The investigator judges other patients who may affect the progress of the clinical study, who may not be able to comply with the agreement, or who cannot cooperate, or who are at risk of research.

研究实施时间：

Study execute time：

从 From 2021-08-20 00:00:00至 To 2024-08-20 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2021-08-20 00:00:00 至 To 2024-01-20 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 71

Group：

test group

Sample size：

干预措施：

卡瑞利珠单抗+GC

干预措施代码：

Intervention：

carrelizumab combined with GC

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 内蒙古自治区 

市(区县)：

  

Country：

China

Province：

Inner Mongolia Autonomous Region

City：

单位(医院)：

 包头市肿瘤医院 

单位级别：

 三级甲等 

Institution
hospital：

Baotou Cancer Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

病理完全缓解率

指标类型：

主要指标

Outcome：

pathologic complete 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：

客观缓解率

指标类型：

次要指标

Outcome：

objective remission 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：

安全性

指标类型：

次要指标

Outcome：

safety

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无病生存期

指标类型：

次要指标

Outcome：

disease free survival

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：

overall survival

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

12个月生存率

指标类型：

次要指标

Outcome：

12-month survival 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：

耐受性

指标类型：

次要指标

Outcome：

tolerance

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

 其它  

说明

Fate of sample：

0thers  

Note：

标本中文名：

尿液

组织：

Sample Name：

Urine

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

Note：

标本中文名：

粪便

组织：

Sample Name：

Stool

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

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 85 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）：

单臂研究，无随机方法

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

Single-arm study, no random method

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）：

文章发表

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

Articles published

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, CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2021-07-21 02:49:31