ChiCTR2200055403 版本V1.3 版本创建时间2022/08/19 14:25:37 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：

 ChiCTR2200055403 

最近更新日期：

Date of Last Refreshed on：

 2022-08-19 14:22:45 

注册时间：

Date of Registration：

 2022-01-08 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

维迪西妥单抗联合卡瑞利珠单抗在局部进展或转移性尿路上皮腺癌、尿路上皮鳞癌患者中的有效性和安全性的开放、单臂、II期临床研究

Public title：

An open-label, single-arm, phase II clinical study of the efficacy and safety of vellicitumab in combination with camrelizumab in patients with locally advanced or metastatic urothelial adenocarcinoma and urothelial squamous cell carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

维迪西妥单抗联合卡瑞利珠单抗在局部进展或转移性尿路上皮腺癌、尿路上皮鳞癌患者中的有效性和安全性的开放、单臂、II期临床研究

Scientific title：

An open-label, single-arm, phase II clinical study of the efficacy and safety of vellicitumab in combination with camrelizumab in patients with locally advanced or metastatic urothelial adenocarcinoma and urothelial squamous cell carcinoma

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：

唐露 

研究负责人：

郭刚 

Applicant：

Tang Lu 

Study leader：

Guo Gang 

申请注册联系人电话：

Applicant telephone：

 +86 15652706812

研究负责人电话：

Study leader's
telephone：

+86 13911275922

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：

 tanglu9106@foxmail.com

研究负责人电子邮件：

Study leader's E-mail：

 greenguo@sina.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：

北京市海淀区永定路69号

研究负责人通讯地址：

北京市海淀区永定路69号

Applicant address：

69 Yongding Road, Haidian District, Beijing

Study leader's address：

69 Yongding 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：

解放军总医院第三医学中心泌尿外科医学部

Applicant's institution：

The Third Medical Center of PLA General Hospital

研究负责人所在单位：

解放军总医院第三医学中心泌尿外科医学部

Affiliation of the Leader：

The Third Medical Center of PLA General 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：

 KY2021-026

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：

中国人民解放军总医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of PLA General Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2021-12-15 00:00:00

伦理委员会联系人：

陈然

Contact Name of the ethic committee：

Chen Ran

伦理委员会联系地址：

北京市海淀区永定路69号

Contact Address of the ethic committee：

69 Yongding Road, Haidian District, Beijing

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：

解放军总医院第三医学中心泌尿外科医学部

Primary sponsor：

The Third Medical Center of PLA General Hospital

研究实施负责（组长）单位地址：

北京市海淀区永定路69号

Primary sponsor's address：

69 Yongding 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)：

解放军总医院第三医学中心泌尿外科医学部

具体地址：

海淀区永定路69号

Institution
hospital：

The Third Medical Center of PLA General Hospital

Address：

69 Yongding Road, Haidian District

经费或物资来源：

维迪西妥单抗和卡瑞利珠单抗由相应厂家提供，试验期间免费

Source(s) of funding：

Vidicitumab and camrelizumab were provided by the respective manufacturers, free of charge during the trial

研究疾病：

尿路上皮鳞癌、尿路上皮腺癌  

Target disease：

Urothelial squamous cell carcinoma, urothelial adenocarcinoma

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：

 II-III期临床试验 

Study phase：

2-3

研究设计：

单臂 

Study design：

Single arm 

研究目的：

探索ADC类药物维迪西妥单抗（RC-48）联合PD-1单抗卡瑞利珠单抗二线治疗不可切除局部晚期或转移性尿路上皮腺癌，尿路上皮鳞癌治疗的安全性和有效性。  

Objectives of Study：

Explore the safety and effectiveness of ADC drug vedicitumab (RC-48) combined with PD-1 monoclonal antibody camrelizumab in second-line treatment of unresectable locally advanced or metastatic urothelial adenocarcinoma and urothelial squamous cell carcinoma.

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.在实施任何试验相关流程之前，签署书面知情同意；
2.年龄≥18岁，且≤85岁；
3.ECOG评分0-1分；
4.受试者接受过以铂类为基础联合紫杉醇或吉西他滨化疗，疾病进展；或铂类不耐受，紫杉醇或吉西他滨化疗后疾病进展；
5.具有组织病理学确诊的尿路上皮鳞癌、尿路上皮腺癌（包括来自肾盂、输尿管、尿道起源允许包含其他组织学变异成分）；
6.所患肿瘤确诊为无法手术切除或手术治疗后复发的局部进展或转移性疾病，且既往至少已经接受过常规化疗后治疗失败，常规化疗方案含有吉西他滨、铂类以及紫杉类。新辅助/辅助化疗结束后6个月内出现疾病进展或复发，如新辅助/辅助化疗以及后续治疗包含上述三种化疗药物，可符合该要求。中心实验室确认的HER2表达：IHC 2+；受试者能够提供HER2检测的肿瘤原发或转移灶部位标本；
7.至少具有一个RECIST1.1标准规定的可测量病灶（可测量病灶未接受过放疗）；既往放疗部位的肿瘤病灶如果证明研究入组时出现进展则认为可测量；
8.预计生存期≥3个月；
9.主要器官功能正常（在入组前14天），即足够的心、骨髓、肝、肾功能；
10.治疗前4周内未接受过系统性皮质类固醇药物治疗，生理性皮质类固醇替代治疗除外；
11.有生殖能力的男性或有怀孕可能性的女性[未行子宫切除术、双侧卵巢切除术或双侧输卵管结扎，或者绝经（停经总时间≥1年）前]，必须在试验过程中使用高度有效的避孕方法（如口服避孕药、宫内避孕器、节制性欲或屏障避孕法结合杀精剂），且在治疗结束后继续避孕12个月；
12.受试者自愿加入研究，签署知情同意书，依从性好，配合随访。

Inclusion criteria

1. Sign written informed consent before implementing any trial-related procedures;
2. Aged 18-85 years;
3. ECOG score 0-1 points;
4. The subject has received platinum-based chemotherapy combined with paclitaxel or gemcitabine, and the disease has progressed; or platinum is intolerant, and the disease has progressed after chemotherapy with paclitaxel or gemcitabine;
5. Urothelial squamous cell carcinoma and urothelial adenocarcinoma with histopathological diagnosis (including origin from renal pelvis, ureter, and urethra are allowed to contain other histological variation components);
6. The tumor is diagnosed with locally advanced or metastatic disease that cannot be surgically removed or recurs after surgical treatment, and has received at least conventional chemotherapy before treatment failure. The conventional chemotherapy regimen contains gemcitabine, platinum and taxane. Disease progression or relapse within 6 months after the end of neoadjuvant/adjuvant chemotherapy, such as neoadjuvant/adjuvant chemotherapy and subsequent treatment including the above three chemotherapy drugs, can meet this requirement. HER2 expression confirmed by central laboratory: IHC 2+; subject can provide primary or metastatic tumor specimens for HER2 detection;
7. There is at least one measurable lesion specified by RECIST1.1 (the measurable lesion has not received radiotherapy); the tumor lesion at the site of previous radiotherapy is considered measurable if it proves that there is progress at the time of study enrollment;
8. Expected survival period >= 3 months;
9. The main organ functions are normal (14 days before enrollment), that is, adequate heart, bone marrow, liver, and kidney functions;
10. Have not received systemic corticosteroid therapy within 4 weeks before treatment, except for physiological corticosteroid replacement therapy;
11. Men with reproductive potential or women with the possibility of pregnancy [without hysterectomy, bilateral oophorectomy, or bilateral tubal ligation, or before menopause (total menopause >= 1 year)], must use a highly effective contraceptive method (eg, oral contraceptives, intrauterine devices, abstinence or barrier contraceptives combined with spermicides) during the trial and continue contraception for 12 months after the end of treatment;
12. The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up.

排除标准：

1.首次给药前5年内诊断为尿路上皮腺癌、尿路上皮腺癌之外的其他恶性疾病（不包括经过根治的皮肤基底细胞癌、皮肤鳞状上皮癌、和/或经过根治性切除的原位癌）；
2.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使用过研究器械治疗；
3.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）；研究给药开始前4周内进行过大型手术且未完全恢复；
4.研究给药开始前4周内接种过活疫苗或计划在研究期间接受任何疫苗；
5.HIV检测结果阳性；
6.活动性乙型肝炎或丙型肝炎患者；HBsAg或HBcAb阳性者同时检测到HBV DNA拷贝数阳性；这类患者研究筛查时必须检测 HBV DNA；HCV抗体检测结果阳性的患者，仅当HCV RNA的PCR检测结果为阴性时，方可入选本研究；
7.妊娠或哺乳期妇女；
8.存在任何严重或不能控制的全身性疾病，例如：
（1）静息心电图在节律、传导或形态上出现有重大且症状严重难以控制的异常，如完全性左束支传导阻滞，Ⅱ度以上心脏传导阻滞，室性心律失常或心房颤动；
（2）不稳定型心绞痛，充血性心力衰竭，纽约心脏病协会（NYHA）分级≥2级的慢性心衰；
（3）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；
（4）血压控制不理想（收缩压＞140mmHg，舒张压＞90mmHg）；
（5）首次给药前1年内存在需要糖皮质激素治疗的非感染性肺炎病史，或当前存在临床活动性间质性肺病；
（6）活动性肺结核；
（7）存在需要全身性治疗的活动性或未能控制的感染；
（8）存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻；
（9）肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎；
（10）糖尿病控制不佳（空腹血糖（FBG）＞10mmol/L）；
（11）尿常规提示尿蛋白≥++，且证实24小时尿蛋白定量＞1.0g者；
（12）存在精神障碍且无法配合治疗的患者；
（13）既往接受过异体造血干细胞移植；
（14）往接受过其他抗体偶联药物治疗；
9.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. Diagnosed with urothelial adenocarcinoma and other malignant diseases other than urothelial adenocarcinoma within 5 years before the first administration (excluding radically treated basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or radically resected carcinoma in situ);
2. Currently participating in interventional clinical research treatment, or have received other investigational drugs or used investigational device treatment within 4 weeks before the first dose;
3. Have not sufficiently recovered from toxicity and/or complications caused by any intervention (ie, <= grade 1 or reached baseline, excluding fatigue or alopecia) prior to initiation of treatment; major surgery within 4 weeks before the start of study administration and incomplete recovery;
4. Have been vaccinated with live vaccines within 4 weeks before the start of the study administration or plan to receive any vaccines during the study;
5. HIV test result is positive;
6. Active hepatitis B or hepatitis C patients; HBsAg or HBcAb positive patients are also tested positive for HBV DNA copy number; such patients must be tested for HBV DNA during research screening; patients with positive HCV antibody test results can be included in this study only when the HCV RNA PCR test results are negative;
7. Pregnant or lactating patients;
8. The presence of any serious or uncontrolled systemic disease, such as:
(1) There are significant abnormalities in the rhythm, conduction or morphology of the resting ECG, and the symptoms are severe and difficult to control, such as complete left bundle branch block, second-degree heart block, ventricular arrhythmia or atrial fibrillation;
(2) Unstable angina pectoris, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) grade >= 2;
(3) Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient cerebral ischemic attack, occurred within 6 months before the treatment;
(4) Poor blood pressure control (systolic blood pressure>140mmHg, diastolic blood pressure>90mmHg);
(5) There is a history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year before the first administration, or there is currently clinically active interstitial lung disease;
(6) Active pulmonary tuberculosis;
(7) There is an active or uncontrolled infection that requires systemic treatment;
(8) Clinically active diverticulitis, abdominal abscess, and gastrointestinal obstruction;
(9) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
(10) Poor control of diabetes (fasting blood glucose (FBG) > 10mmol/L);
(11) Urine routine indicates urine protein >=++, and confirmed 24-hour urine protein quantitative >1.0g;
(12) Patients with mental disorders and unable to cooperate with treatment;
(13) Received allogeneic hematopoietic stem cell transplantation in the past;
(14) Received other antibody-conjugated drug therapy in the past;
9. Abnormal medical history or disease evidence, treatment or laboratory test values that may interfere with the test results, prevent subjects from participating in the research throughout the study, or the researcher considers other situations that are not suitable for inclusion, or the researcher believes that there are other potential risks and are not suitable to participate in this study.

研究实施时间：

Study execute time：

从 From 2022-01-01 00:00:00至 To 2023-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-01-01 00:00:00 至 To 2023-06-30 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 12

Group：

Experimental group

Sample size：

干预措施：

维迪西妥单抗+卡瑞利珠单抗

干预措施代码：

Intervention：

Vidicitumab + Camrelizumab

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)：

 解放军总医院第三医学中心泌尿外科医学部 

单位级别：

 三级甲等 

Institution
hospital：

The Third Medical Center of PLA General 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：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

Sample Name：

Null

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）：

该研究为非随机对照研究

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

The study was a non-randomized controlled study

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）：

不共享

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

NA

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：

病例报告表

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

CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2022-01-08 11:27:15