中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500111737
最近更新日期： Date of Last Refreshed on：	2025-11-05 11:06:15
注册时间： Date of Registration：	2025-11-05 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	伏罗尼布联合特瑞普利单抗一线治疗转移性肾透明细胞癌单臂、单中心临床研究
Public title：	A Single-Arm, Single-Center Clinical Study of Vorolanib Combined with Toripalimab as First-Line Therapy for Metastatic Clear Cell Renal Cell Carcinoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	伏罗尼布联合特瑞普利单抗一线治疗转移性肾透明细胞癌单臂、单中心临床研究
Scientific title：	A Single-Arm, Single-Center Clinical Study of Vorolanib Combined with Toripalimab as First-Line Therapy for Metastatic Clear Cell 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：	朱国栋	研究负责人：	朱国栋
Applicant：	Guodong Zhu	Study leader：	Guodong Zhu
申请注册联系人电话： Applicant telephone：	+86 150 0291 5619	研究负责人电话： Study leader's telephone：	+86 150 0291 5619
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：	gdzhu@xjtu.edu.cn	研究负责人电子邮件： Study leader's E-mail：	gdzhu@xjtu.edu.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：	陕西省西安市雁塔区雁塔西路277号	研究负责人通讯地址：	陕西省西安市雁塔区雁塔西路277号
Applicant address：	No. 277, Yanta West Road, Yanta District, Xi'an City, Shaanxi Province	Study leader's address：	No. 277, Yanta West Road, Yanta District, Xi'an City, Shaanxi Province
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：	西安交通大学第一附属医院
Applicant's institution：	The First Affiliated Hospital of Xi'an Jiaotong University
研究负责人所在单位：	西安交通大学第一附属医院
Affiliation of the Leader：	The First Affiliated Hospital of Xi'an Jiaotong University

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：	2025伦审医研字第(788)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：	西安交通大学第一附属医院医学伦理委员会
Name of the ethic committee：	The Medical Ethics Committee of The First Affiliated Hospital of Xi'an Jiaotong University
伦理委员会批准日期： Date of approved by ethic committee：	2025-09-24 00:00:00
伦理委员会联系人：	易秋月
Contact Name of the ethic committee：	QiuYue Yi
伦理委员会联系地址：	陕西省西安市雁塔区雁塔西路277号
Contact Address of the ethic committee：	No. 277, Yanta West Road, Yanta District, Xi'an City, Shaanxi Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 29 8532 3473	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：

西安交通大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Xi'an Jiaotong University

研究实施负责（组长）单位地址：

陕西省西安市雁塔区雁塔西路277号

Primary sponsor's address：

No. 277, Yanta West Road, Yanta District, Xi'an City, Shaanxi Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	陕西省	市(区县)：
Country：	China	Province：	Shaanxi Province	City：
单位(医院)：	西安交通大学第一附属医院	具体地址：	陕西省西安市雁塔区雁塔西路277号
Institution hospital：	The First Affiliated Hospital of Xi'an Jiaotong University	Address：	No. 277, Yanta West Road, Yanta District, Xi'an City, Shaanxi Province

经费或物资来源：

自筹

Source(s) of funding：

Self - funded

研究疾病：

肾透明细胞癌

Target disease：

Clear cell renal cell carcinoma(ccRCC)

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：评价伏罗尼布联合特瑞普利单抗一线治疗转移性肾透明细胞癌患者的有效性，主要研究终点是 PFS。次要研究目的：价伏罗尼布联合特瑞普利单抗一线治疗转移性肾透明细胞癌患者的客观缓解率 ORR，疾病控制率 DCR，总生存期 OS，12 个月&24 个月 OS 率和安全性。

Objectives of Study：

Primary Objective: To evaluate the efficacy of vorolanib in combination with toripalimab as first-line therapy for patients with metastatic clear cell renal cell carcinoma (ccRCC). The primary endpoint is progression-free survival (PFS). Secondary Objectives: To assess the objective response rate (ORR), disease control rate (DCR), overall survival (OS), 12-month and 24-month OS rates, and safety profile of vorolanib combined with toripalimab as first-line treatment for metastatic clear cell renal cell carcinoma (ccRCC).

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. The subject voluntarily participates in this study and signs the informed consent form.
2. Age: 18 - 80 years old (at the time of signing the informed consent form).
3. Pathologically or histologically confirmed unresectable or metastatic clear - cell renal cell carcinoma.
4. No prior systemic drug therapy for the advanced - stage disease.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0 - 1; estimated survival time exceeding 3 months.
6. Representative formalin - fixed, paraffin - embedded tumor specimens or fresh - frozen tissue specimens that can confirm the diagnosis of clear - cell renal cell carcinoma, accompanied by relevant pathological reports. The specimens can be collected through surgical resection or biopsy of the primary tumor, or biopsy or resection of metastatic lesions.
7. Confirmed to have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1).
8. Good major organ function and adequate hematological function, meeting the following criteria:
Absolute neutrophil count (ANC) >= 1.5×10^9/L without the use of granulocyte colony - stimulating factor in the recent 14 days.
Platelet count >= 90×10^9/L without platelet transfusion or the use of thrombopoietin in the recent 14 days.
Hemoglobin > 9 g/dL without blood transfusion or the use of erythropoietin in the recent 14 days.
9.  Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) <= 2.5 times the upper limit of normal (ULN). If the patient has bone metastases, ALP <= 5 times ULN.
10. Serum bilirubin <=1.5×ULN. Patients with known Gilbert's syndrome can be enrolled if their serum bilirubin level is <=3 times ULN.
11.  Serum albumin >= 2.8 g/dL.
12. Creatinine <= 2.0×ULN or calculated creatinine clearance >= 30 mL/min.
13. Urine protein/creatinine ratio (UPCR)<=1 mg/mg (<=113.2 mg/mmol).
14. For women who are not post - menopausal (amenorrhea for less than 12 months) or surgically sterile (no ovaries and/or uterus): agree to use two appropriate contraceptive methods, including at least one method with an annual failure rate of <= 1%.
15.For female subjects of childbearing potential, a urine or serum pregnancy test should be performed within 3 days before the first dose of the study drug (Cycle 1, Day 1) and the result should be negative. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Non - childbearing - potential women are defined as those who have been post - menopausal for at least 1 year, or have undergone surgical sterilization or hysterectomy.
16. If there is a risk of pregnancy, all subjects (regardless of gender) should use contraceptive measures with an annual failure rate of less than 1% throughout the treatment period and until 120 days after the last dose of the study drug (or 180 days after the last dose of the chemotherapy drug).
17.Be able to understand and comply with the protocol requirements and must sign the informed consent document.

排除标准：

1.既往接受过针对晚期疾病阶段的系统治疗药物或合并其他肿瘤； 2.治疗开始前2周内接受过任何类型的小分子激酶抑制剂； 3.在治疗开始的4周内接受过任何类型的抗癌抗体，细胞毒性抗癌治疗或任何其他研究药物； 4.已知的脑或脊髓恶性肿瘤或脑脊膜疾病； 5.需要止痛药的患者在研究开始时必须处于稳定的治疗方案中； 6.有活动性中枢神经系统（CNS）转移的受试者，如果受试者的CNS转移能够充分治疗，并且受试者的神经系统症状能够在入选前至少2周恢复到基线水平（与CNS治疗有关的残留体征或症状除外），则可以参加研究。此外，受试者还必须是不用皮质类固醇的受试者，或接受剂量稳定或逐渐降低的＜=10mg/天的强的松（或等价物）； 7.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； 8.首次给药前2年内发生过需要全身性治疗（例如糖皮质激素或免疫抑制剂）的活动性自身性免疫疾病。替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性糖皮质激素等）不视为全身性治疗； 9.研究首次给药前7天内正在接受全身性糖皮质激素治疗（不包括喷鼻、吸入性或其他途径的局部糖皮质激素）或任何其他形式的免疫抑制疗法；注：允许使用生理剂量的糖皮质激素（＜=10 mg/天的泼尼松或等效药物）； 10.已知对本研究药物活性成分或辅料过敏者； 11.妊娠或哺乳期妇女； 12.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）； 13.已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）； 14.未经治疗的活动性乙肝（定义为HBsAg阳性同时检测到HBV-DNA拷贝数大于所在研究中心检验科正常值上限）；注：符合下列标准的乙肝受试者亦可入组：首次给药前HBV病毒载量＜1000拷贝/mL（200 IU/mL），受试者应在整个研究治疗期间接受抗HBV治疗避免病毒再激活；对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活； 15.活动性的HCV感染受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）； 16.首次给药之前（第1周期，第1天）30天内接种过活疫苗；注：允许首次给药前30天内接受针对季节性流感的注射用灭活病毒疫苗；但是不允许接受鼻内用药的减毒活流感疫苗。 17.存在任何严重或不能控制的全身性疾病，例如：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；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；入组前6个月内出现心肌梗死；血压控制不理想（收缩压＞140 mmHg，舒张压＞90 mmHg）；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；活动性肺结核；存在需要全身性治疗的活动性或未能控制的感染；存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻；肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎；糖尿病控制不佳（空腹血糖（FBG）＞10mmol/L）；尿常规提示尿蛋白>=++，且证实24小时尿蛋白定量＞1.0 g者；存在精神障碍且无法配合治疗的患者； 18.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或存在其他潜在风险不适合参加本研究。

Exclusion criteria：

1. History of prior systemic therapy for advanced - stage disease or concomitant other tumors; 2. Receipt of any type of small - molecule kinase inhibitor within 2 weeks before the start of treatment; 3. Receipt of any type of anticancer antibody, cytotoxic anticancer therapy, or any other investigational drug within 4 weeks before the start of treatment; 4. Known malignant tumors of the brain or spinal cord or meningeal diseases; 5.Patients who require analgesics must be on a stable treatment regimen at the start of the study; 6. Subjects with active central nervous system (CNS) metastases can participate in the study if their CNS metastases can be adequately treated and their neurological symptoms can return to the baseline level at least 2 weeks before enrollment (excluding residual signs or symptoms related to CNS treatment). In addition, subjects must be either not using corticosteroids or receiving prednisone (or equivalent) at a stable or tapering dose of <=10 mg/day; 7. Currently participating in an interventional clinical study treatment or having received other investigational drugs or used investigational device treatments within 4 weeks before the first dose; 8. History of active autoimmune disease requiring systemic treatment (e.g., glucocorticoids or immunosuppressants) within 2 years before the first dose. Substitute therapies (e.g., thyroid hormone, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic treatment; 9. Receiving systemic glucocorticoid therapy (excluding nasal, inhaled, or other local glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first dose of the study; Note: The use of physiologic doses of glucocorticoids (<=10 mg/day of prednisone or equivalent) is allowed; 10. Known allergy to the active ingredients or excipients of the study drugs; 11.Pregnant or lactating women; 12.Not having fully recovered (i.e., <=Grade 1 or returned to baseline, excluding fatigue or alopecia) from the toxicity and/or complications caused by any previous interventions before the start of treatment; 13. Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibodies); 14. Untreated active hepatitis B (defined as positive HBsAg and detectable HBV - DNA copy number greater than the upper limit of normal of the local laboratory); Note: Hepatitis B subjects meeting the following criteria can also be enrolled:  HBV viral load <1000 copies/mL (200 IU/mL) before the first dose. Subjects should receive anti - HBV treatment throughout the study treatment period to prevent viral reactivation;  For subjects who are anti - HBc (+), HBsAg (−), anti - HBs (−), and HBV viral load (−), preventive anti - HBV treatment is not required, but close monitoring for viral reactivation is needed; 15. Subjects with active HCV infection (positive HCV antibody and HCV - RNA level above the lower limit of detection); 16.Vaccination with live vaccines within 30 days before the first dose (Cycle 1, Day 1); Note: Injection of inactivated seasonal influenza virus vaccine within 30 days before the first dose is allowed; however, intranasal attenuated live influenza vaccine is not allowed. 17. Presence of any severe or uncontrolled systemic diseases, such as: Significant and severely symptomatic and difficult - to - control abnormalities in rhythm, conduction, or morphology on resting electrocardiogram, such as complete left - bundle branch block, second - degree or higher heart block, ventricular arrhythmias, or atrial fibrillation; Unstable angina, congestive heart failure, chronic heart failure of New York Heart Association (NYHA) grade>=2; Myocardial infarction within 6 months before enrollment; Poorly controlled blood pressure (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg); History of non - infectious pneumonia requiring glucocorticoid treatment within 1 year before the first dose or currently having clinically active interstitial lung disease; Active tuberculosis; Presence of active or uncontrolled infections requiring systemic treatment; Presence of clinically active diverticulitis, intra - abdominal abscess, or gastrointestinal obstruction; Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; Poorly controlled diabetes (fasting blood glucose (FBG) >10 mmol/L); Urinalysis indicating urine protein >=++ and confirmed 24 - hour urine protein quantification >1.0 g; Patients with mental disorders who cannot cooperate with treatment; 18. History, evidence of diseases, treatment, or abnormal laboratory test values that may interfere with the trial results, prevent the subject from fully participating in the study, or other situations considered unsuitable for enrollment by the investigator or other potential risks that make the subject unfit to participate in this study.

研究实施时间：

Study execute time：

从 From 2025-07-31 00:00:00至 To 2029-06-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-11-30 00:00:00 至 To 2027-11-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	30
Group：	Treatment group	Sample size：	30
干预措施：	伏罗尼布+特瑞普利单抗	干预措施代码：
Intervention：	Vorolanib + Toripalimab	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	陕西省	市(区县)：
Country：	China	Province：	Shaanxi Province	City：
单位(医院)：	西安交通大学第一附属医院	单位级别：	三甲
Institution hospital：	The First Affiliated Hospital of Xi'an Jiaotong University	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：	Progression-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：	客观缓解率	指标类型：	次要指标
Outcome：	Objective Response 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：	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：	OS 率	指标类型：	次要指标
Outcome：	overall survival (OS) rates	Type：	Secondary indicator
测量时间点：	12 个月 & 24 个月	测量方法：
Measure time point of outcome：	12-month and 24-month	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：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	无	组织：
Sample Name：	None	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	80	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:

不公开/Private

盲法：
Blinding：

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）：	本研究不共享原始数据
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The original data of this study will not be shared.
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：	使用CRF表进行数据采集和管理
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Data collection and management will be carried out using CRF forms.
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2025-11-05 11:06:11