ChiCTR2300070660 版本V1.1 版本创建时间2023/05/28 22:02:19 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：

ChiCTR2300070660 

最近更新日期：

Date of Last Refreshed on：

2023-04-19 15:56:46 

注册时间：

Date of Registration：

2023-04-19 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

培唑帕尼联合替雷利珠单抗治疗初治中危及高危转移性肾细胞癌的安全性及疗效性的临床研究

Public title：

Clinical study on safety and efficacy of pazopanib plus tislelizumab as the first-line therapy for intermediate and poor risk advanced renal cell carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

培唑帕尼联合替雷利珠单抗治疗初治中危及高危转移性肾细胞癌的安全性及疗效性的临床研究

Scientific title：

Clinical study on safety and efficacy of pazopanib plus tislelizumab as the first-line therapy for intermediate and poor risk advanced renal 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：

董培 

研究负责人：

董培 

Applicant：

Dong Pei 

Study leader：

Dong Pei 

申请注册联系人电话：

Applicant telephone：

+86 13512738496

研究负责人电话：

Study leader's telephone：

+86 13512738496

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：

dongpei@sysucc.org.cn

研究负责人电子邮件：

Study leader's E-mail：

dongpei@sysucc.org.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：

广州市越秀区东风东路651号

研究负责人通讯地址：

广州市越秀区东风东路651号

Applicant address：

651 Dongfeng East Road, Yuexiu District, Guangzhou, China

Study leader's address：

651 Dongfeng East Road, Yuexiu District, Guangzhou, 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：

中山大学肿瘤防治中心泌尿外科

Applicant's institution：

Department of Urology, Sun Yat-sen University Cancer Center

研究负责人所在单位：

中山大学肿瘤防治中心泌尿外科

Affiliation of the Leader：

Department of Urology, Sun Yat-sen University Cancer Center

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

SL-B2021-312-03

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：

中山大学肿瘤防治中心伦理委员会

Name of the ethic committee：

Ethics Committee of Cancer Center, Sun Yat-sen University

伦理委员会批准日期：

Date of approved by ethic committee：

2021-12-03 00:00:00

伦理委员会联系人：

符立梧

Contact Name of the ethic committee：

Liwu Fu

伦理委员会联系地址：

广东省广州市先烈南路23号翠园楼316室

Contact Address of the ethic committee：

Room 316, Cuiyuan Building, 23 Xianlie South Road, Guangzhou City, Guangdong Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 20 87343009

伦理委员会联系人邮箱：

Contact email of the ethic committee：

LiwuFu@sysucc.org.cn

研究实施负责（组长）单位：

中山大学肿瘤防治中心泌尿外科

Primary sponsor：

Department of Urology, Sun Yat-sen University Cancer Center

研究实施负责（组长）单位地址：

广州市越秀区东风东路651号

Primary sponsor's address：

651 Dongfeng East Road, Yuexiu District, Guangzhou, 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)：

广东省

市(区县)：

广州

Country：

China

Province：

Guangdong province

City：

Guangzhou

单位(医院)：

中山大学肿瘤防治中心泌尿外科

具体地址：

广州市越秀区东风东路651号

Institution
hospital：

Department of Urology, Sun Yat-sen University Cancer Center

Address：

651 Dongfeng East Road, Yuexiu District, Guangzhou, China

经费或物资来源：

中山大学肿瘤防治中心泌尿外科

Source(s) of funding：

Department of Urology, Sun Yat-sen University Cancer Center

Target disease：

Renal cell carcinoma

Target disease code：

研究类型：

干预性研究

Study type：

Interventional 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：

评价培唑帕尼联合替雷利珠单抗在中危及高危初治转移性肾细胞癌患者的疗效性和安全性  

Objectives of Study：

To evaluate the efficacy and safety of pazopanib plus tislelizumab as the first-line therapy for intermediate and poor risk advanced renal 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.受试者自愿加入本研究，并签署知情同意书，依从性好，配合随访；
2.既往接受过根治性肾切除术，组织病理学证实为透明细胞癌，影像或病理诊断复发；或初诊为转移性肾癌，组织病理学及影像学诊断为多发转移性肾透明细胞癌；
3.根据转移性肾癌预后危险因素评分（IMDC），具有至少一个危险因素（中危：1～2个危险因素；高危：≥3个危险因素）：1）确诊原发癌至全身治疗时间小于1年；2）Karnofsky评分小于80分；3）血红蛋白 小于正常值下限；4）血清钙大于正常值上限；5）中性粒细胞大于正常值上限；6）血小板计数大于正常值上限；
4.入组时根据RECIST1.1实体瘤疗效评价标准评估至少存在1个可测量病灶；
5.受试者未接受过其他系统一线靶向治疗，包括舒尼替尼，索拉非尼等；
6.育龄妇女必须已经采取可靠的避孕措施或在入组前7天内进行妊娠试验（血清或尿液），且结果为阴性，并且愿意在试验期间和末次给予试验药物后8周采用适当的方法避孕。对于男性，须同意在试验期间和末次给予试验药物后8周采用适当的方法避孕或已手术绝育；
7.ECOG评分为0或1分；
8.主要器官功能正常，即符合下列标准：
（1）血常规检查标准需符合（14天内未输血及血制品，未使用G-CSF及其他造血刺激因子纠正）：
a．血红蛋白（HB）≥90 g/L（14天内未输血）；
b．中性粒细胞（ANC）≥1.5×109 /L；
c．血小板计数（PLT）≥80×109 /L；
（2）生化检查需符合以下标准：
a. 总胆红素（TBIL）≤1.5×ULN（正常值上限）；
b．谷丙转氨酶（ALT）、谷草转氨酶（AST）≤2.5×ULN；
c．血浆肌酐 ≤1.5 ULN，且肌酐清除率≥60mL/min；
d．活化部分凝血活酶时间（APTT）和国际标准化比值（INR）≤1.5×ULN（对于使用稳定剂量的抗凝治疗如低分子肝素或者华法林且INR在抗凝血剂的预期治疗范围内可以筛选）；
f.促甲状腺激素（TSH）≤ULN；如果异常应考察T3和T4水平，T3和T4水平水平正常则可以入选；
9.超声心动图或多层采集扫描评估左心室射血分数≥正常下限；
10.预期寿命大于1年；
11.年龄18-75周岁之间的男性或女性患者。

Inclusion criteria

1. The subjects voluntarily joined the study and signed the informed consent with good compliance and follow-up;
2. Previous radical nephrectomy, histopathologically confirmed clear cell carcinoma, imaging or pathological diagnosis of recurrence;
Or the patient was diagnosed with metastatic renal carcinoma at first, and was diagnosed with multiple metastatic renal clear cell carcinoma by histopathology and imaging;
3. According to the prognostic Risk factor Score (IMDC) of metastatic renal cancer, having at least one risk factor (medium risk: 1 to 2 risk factors;
High risk: ≥3 risk factors) : 1) The time from diagnosis of primary cancer to systemic treatment is less than 1 year;
2) Karnofsky score is less than 80 points;
3) Hemoglobin is lower than the lower limit of normal value;
4) Serum calcium is greater than the upper limit of normal value;
5) neutrophils greater than the upper limit of normal;
6) Platelet count is greater than the upper limit of normal value;
4. At least one measurable lesion was evaluated according to RECIST1.1 solid tumor efficacy evaluation criteria upon enrollment;
5. The subjects had not received other first-line targeted therapies, including Sunitinib, sorafenib, etc.;
6. Women of childbearing age must have been using reliable contraception or have had a pregnancy test (serum or urine) with negative results within 7 days prior to inclusion and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last test drug administration.
For males, consent is required to use an appropriate method of contraception or surgical sterilization during the trial period and 8 weeks after the last administration of the trial drug;
7. The ECOG score is 0 or 1;
8. If the major organs are functioning normally, the following criteria are met:
(1) The standard of blood routine examination shall be met (no blood transfusion or blood products within 14 days, no correction by G-CSF and other hematopoietic stimulating factors) :
a.
Hemoglobin (HB) ≥90 g/L (no blood transfusion within 14 days);
b.
Neutrophil (ANC) ≥1.5×109 /L;
c.
Platelet count (PLT) ≥80×109 /L;
(2) Biochemical examination shall meet the following standards:
a. Total bilirubin (TBIL) ≤1.5×ULN (upper limit of normal);
b.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5×ULN;
c.
Plasma creatinine ≤1.5 ULN, and creatinine clearance ≥60mL/min;
d.
Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5×ULN (for stable dose anticoagulant therapy such as low molecular weight heparin or warfarin and INR within the expected treatment range of anticoagulants can be screened);
f. Thyroid stimulating hormone (TSH) ≤ULN;
If abnormal, T3 and T4 levels should be investigated, and normal T3 and T4 levels can be included;
9. Left ventricular ejection fraction ≥ lower normal limit was evaluated by echocardiography or multilayer acquisition scanning;
10. Life expectancy greater than 1 year;
11. Male or female patients aged 18-75 years.

排除标准：

1.患者正在参加其他临床研究或距离前一项临床研究治疗结束时间不足4周；
2.在研究过程中，预计受试者需要任何其他形式的全身或局部抗肿瘤治疗；
3. 接受过以下的任何治疗：
? ?既往接受过抗PD-1、抗PD-L1抗体或者抗CTLA-4抗体治疗
? ?同时入组另外一项临床研究，除非是观察性（非干预性）临床研究或者干预新临床研究随访
? ?首次使用研究药物前2周内需要给予皮质类固醇（每天大于10mg泼尼松等效剂量）或者其他免疫抑制剂进行系统治疗的受试者，除外针对局部炎症和预防过敏及恶心、呕吐使用皮质类固醇的情况。在没有活动性自身免疫疾病的情况下，允许吸入或局部使用类固醇和剂量大于10mg/天泼尼松疗效剂量的肾上腺皮质激素替代；
? ?接种过抗肿瘤疫苗或者研究药物首次给药前4周内曾接种过活疫苗；
? ?首次使用研究药物前4周内接受过大手术或者严重外伤。
4.受试者在首次给药前5年内有恶性肿瘤病史（研究中的疾病除外）；
5.有中枢神经系统转移瘤；
6.具有明显影响口服药物吸收的因素，如无法吞咽、慢性腹泻和肠梗阻等；
7.受试者患有间质性肺炎或其他肺炎病史；
8.活动性消化性溃疡病，炎性肠病，溃疡性结肠炎或其他胃肠道疾病，发生穿孔的风险增加；开始研究治疗前4周内有腹部瘘的病史，胃肠道穿孔或腹腔内脓肿；
9. 未经治疗的活动性肝炎（乙肝：HBsAg阳性且HBV DNA≥ 500IU/mL；丙肝：HCV RNA阳性且肝功能异常）；合并乙肝及丙肝共同感染；
10.存在需要全身治疗的活动性感染；
11.校正QT间隔持续时间（QTc）延长；
12.患有严重的心血管疾病：Ⅱ级以上心肌缺血或心肌梗塞、控制不良的心律失常（包括QTc间期男性≥450 ms、女性≥470 ms）；按NYHA标准，Ⅲ～Ⅳ级心功能不全，或心脏彩超检查提示左室射血分数（LVEF）＜50%者；
13.高血压控制不佳；
14.入组前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；
15.有任何未愈合的伤口，骨折或溃疡，或有症状的周围血管疾病；
16.凝血功能异常（INR＞1.5或凝血酶原时间（PT）＞ULN+4秒或APTT >1.5 ULN），具有出血倾向或正在接受溶栓或抗凝治疗；
注：在凝血酶原时间国际标准化比值（INR）≤ 1.5的前提下，允许以预防目的使用小剂量肝素（成人每日用量为0.6万~1.2万U）或小剂量阿司匹林（每日用量≤ 100 mg）；
17.入组前3个月内出现临床显著的咯血（每日咯血大于50ml）；或显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、出血性胃溃疡、基线期大便潜血++及以上，或患有脉管炎等；
18.已知的支气管内病变和/或浸润主要肺血管的病变增加了肺出血的风险；
19.有同类药物（与替雷利珠单抗、培唑帕尼或有相似化学或生物组分的药物）过敏史、过敏体质或现患过敏疾病者；
20.在第一剂研究治疗药物后的14天内服用了方案中列出的所有违禁药物。在首次给予研究治疗药物前30天内，受试者已接受或将接受活疫苗；
21. 有活动性的自身免疫性疾病、自身免疫性疾病史（如间质性肺炎、结肠炎、肝炎、垂体炎、血管炎、肾炎、甲状腺功能亢进症、甲状腺功能减退症，包括但不限于这些疾病和综合症）；使用稳定剂量的甲状腺替代激素治疗的自身免疫街道的甲状腺功能减退症；使用稳定剂量的胰岛素一型糖尿病；但不包括白癜风或已痊愈的童年时代哮喘/过敏，成人后无需任何干预的患者；
22.存在其他严重身体或精神疾病或实验室检查异常，可能增加参与研究的风险，或干扰研究结果，以及研究者认为不适合参与本研究的患者。

Exclusion criteria：

1. Patients are participating in other clinical studies or less than 4 weeks after the end of the previous clinical study;
2. Subjects are expected to require any other form of systemic or local antitumor therapy during the study;
3. Received any of the following treatments:
? ? always received PD - 1 resistance, resistance to PD - L1 antibodies or CTLA 4 resistant treatment
? ? to enroll another clinical research at the same time, unless it is observational clinical research or intervention (non intrusive) new clinical follow-up study
? ? within 2 weeks before first use of study drugs need to be given corticosteroid (more than 10 mg daily prednisone dose equivalent) or other immune inhibitors for treatment of the subjects system, except for the local inflammation and prevent allergy and nausea, vomiting, use of corticosteroids.
In the absence of active autoimmune disease, inhaled or topical steroid and adrenocortical hormone replacement at doses greater than the therapeutic dose of 10mg/ day prednisone are permitted;
? ? received anti-tumor vaccine or drug the first delivery within 4 weeks before had been vaccinated live vaccine;
? ? within 4 weeks before first use of study drugs too much surgery or severe trauma.
4. The subject has a history of malignant tumors (other than the disease under study) within 5 years prior to the initial administration;
5. Metastatic tumor of central nervous system;
6. Significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
7. The subject has a history of interstitial pneumonia or other pneumonia;
8. Increased risk of perforation from active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal diseases;
A history of abdominal fistula, gastrointestinal perforation, or intraperitoneal abscess was studied 4 weeks before treatment.
9. Untreated active hepatitis (Hepatitis B: HBsAg positive with HBV DNA≥ 500IU/mL;
Hepatitis C: HCV RNA positive and abnormal liver function);
Combined with hepatitis B and hepatitis C co-infection;
10. There are active infections that require systemic treatment;
11. Correction of QT interval duration (QTc) extension;
12. Severe cardiovascular disease: Grade Ⅱ or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450 ms in men and 470 ms in women);
According to NYHA criteria, patients with grade Ⅲ to Ⅳ cardiac insufficiency or left ventricular ejection fraction (LVEF) < 50% indicated by color Doppler examination;
13. Poor hypertension control;
14. Arteriovenous thrombosis events, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc. occurred within 6 months before enrollment;
15. There is any open wound, fracture or ulcer, or symptomatic peripheral vascular disease;
16. Abnormal coagulation function (INR >1.5 or prothrombin time (PT) > ULN+4 seconds or APTT >1.5 ULN), bleeding tendency or receiving thrombolytic or anticoagulant therapy;
Note: Under the premise of INR ≤ 1.5, low-dose heparin (adult daily dose: 0.6000-12,000 U) or low-dose aspirin (daily dose: 100 mg or less) is allowed for prophylactic purposes.
17. Clinically significant hemoptysis (daily hemoptysis > 50ml) occurred within 3 months before enrollment;
Or significant clinical bleeding symptoms or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ or above, or suffering from vasculitis;
18. There are known intrabronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage;
19. People who have a history of, are allergic to, or currently suffer from allergic diseases to the same drugs (drugs with similar chemical or biological components as tirelizumab, Pezopanib or drugs);
20. All prohibited substances listed in the protocol were taken within 14 days of the first dose of the study treatment drug.
Subjects have received or will receive live vaccine within 30 days prior to the initial administration of the study therapy;
21. History of active autoimmune diseases, autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, pituitaritis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes);
Autoimmune street hypothyroidism treated with a steady dose of thyroid replacement hormone;
Use a steady dose of insulin for type 1 diabetes;
But does not include vitiligo or cured childhood asthma/allergy, adult without any intervention;
22. The presence of other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of participation in the study or interfere with the study results, as well as patients deemed unsuitable for participation in the study by the investigator.

研究实施时间：

Study execute time：

从 From 2023-04-15 00:00:00至 To 2025-04-15 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-04-20 00:00:00 至 To 2024-04-20 00:00:00  

干预措施：

Interventions：

组别：

试验干预组

样本量：

13

Group：

Experimental intervention group

Sample size：

干预措施：

替雷利珠单抗（iv, Q3W）联合培唑帕尼（400mg, PO）

干预措施代码：

Intervention：

Tislelizumab (iv, Q3W) plus Pazopanib (400mg, PO)

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广东省 

市(区县)：

 广州 

Country：

China 

Province：

Guangdong province 

City：

Guangzhou 

单位(医院)：

中山大学肿瘤防治中心 

单位级别：

三级医院 

Institution
hospital：

Sun Yat-sen University Cancer Center

Level of the institution：

tertiary hospital

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 remission 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：

无进展生存时间

指标类型：

次要指标

Outcome：

progression-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：

安全性指标

指标类型：

次要指标

Outcome：

Safety indicators

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

培唑帕尼血药浓度

指标类型：

附加指标

Outcome：

Pazopanib plasma concentrations

Type：

Additional indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肿瘤组织全外显子测序

指标类型：

附加指标

Outcome：

Tumor tissue whole exome sequencing

Type：

Additional indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

血液标本转录组分析

指标类型：

附加指标

Outcome：

Transcriptome analysis of blood samples

Type：

Additional 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：

肾细胞癌组织

Sample Name：

blood

Tissue：

Renal cell carcinoma 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）：

无

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

None

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）：

学术期刊

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

academic journal

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：

  2023-04-19 15:54:57