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：	ChiCTR2600122387
最近更新日期： Date of Last Refreshed on：	2026-04-13 15:51:32
注册时间： Date of Registration：	2026-04-13 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	SBRT联合PD-1/CTLA-4双特异性抗体(艾帕洛利托沃瑞利单抗)和化疗在复发/寡转移性胰腺癌中的安全性和疗效研究
Public title：	Safety and Efficacy of SBRT Combined with a PD-1/CTLA-4 Bispecific Antibody and Chemotherapy in Recurrent/Oligometastatic Pancreatic Cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	SBRT联合PD-1/CTLA-4双特异性抗体(艾帕洛利托沃瑞利单抗)和化疗在复发/寡转移性胰腺癌中的安全性和疗效研究
Scientific title：	Safety and Efficacy of SBRT Combined with a PD-1/CTLA-4 Bispecific Antibody and Chemotherapy in Recurrent/Oligometastatic Pancreatic 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：	水永杰	研究负责人：	水永杰
Applicant：	Yongjie Shui	Study leader：	Yongjie Shui
申请注册联系人电话： Applicant telephone：	+86 571 8778 3521	研究负责人电话： Study leader's telephone：	+86 571 8778 3521
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：	shui-yongjie@zju.edu.cn	研究负责人电子邮件： Study leader's E-mail：	syjhz@163.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：	浙江省杭州市上城区解放路88号	研究负责人通讯地址：	浙江省杭州市上城区解放路88号
Applicant address：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province	Study leader's address：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang 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：	浙江大学医学院附属第二医院
Applicant's institution：	The second affiliated hospital of Zhejiang University school of medicine
研究负责人所在单位：	浙江大学医学院附属第二医院
Affiliation of the Leader：	The second affiliated hospital of Zhejiang University school of medicine

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）伦审研第（1209）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：	浙江大学医学院附属第二医院科研伦理委员会
Name of the ethic committee：	Human Research Ethics Committee, The Second Affiliated Hospital of Zhejiang University School of Medicine
伦理委员会批准日期： Date of approved by ethic committee：	2025-08-25 00:00:00
伦理委员会联系人：	陈泽鑫
Contact Name of the ethic committee：	Chen Zexin
伦理委员会联系地址：	浙江省杭州市上城区解放路88号
Contact Address of the ethic committee：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 571 87783914	伦理委员会联系人邮箱： Contact email of the ethic committee：	chenzexin@zju.edu.cn

研究实施负责（组长）单位：

浙江大学医学院附属第二医院

Primary sponsor：

The second affiliated hospital of Zhejiang University school of medicine

研究实施负责（组长）单位地址：

浙江省杭州市上城区解放路88号

Primary sponsor's address：

No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang 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)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	浙江大学医学院附属第二医院	具体地址：	浙江省杭州市上城区解放路88号
Institution hospital：	The second affiliated hospital of Zhejiang University school of medicine	Address：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province

经费或物资来源：

国家自然科学基金

Source(s) of funding：

National National Science Foundation of China

研究疾病：

复发/寡转移性胰腺癌

Target disease：

Recurrent/Oligometastatic Pancreatic 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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

1.主要目的评估SBRT联合艾帕洛利托沃瑞利单抗和化疗在复发/寡转移性胰腺癌中的疾病客观应答率（ORR）； 2.次要目的 (1)评估SBRT联合艾帕洛利托沃瑞利单抗和化疗在复发/寡转移性胰腺癌中的疾病控制率（DCR）; (2)评估SBRT联合艾帕洛利托沃瑞利单抗和化疗在复发/寡转移性胰腺癌中的反应持续时间（DOR）; (3)评估SBRT联合艾帕洛利托沃瑞利单抗和化疗在复发/寡转移性胰腺癌中的无进展生存期（PFS）; (4)评估SBRT联合艾帕洛利托沃瑞利单抗和化疗在复发/寡转移性胰腺癌中的总生存期（OS）; (5)评估SBRT联合艾帕洛利托沃瑞利单抗和化疗的安全性和耐受性：包括严重不良事件（SAE）和免疫相关不良事件（irAE）的发生率，SAE/irAE导致治疗终止的发生率; (6)探索SBRT前后连续采集的外周血标本中生物标志物（包括但不限于CD8/Treg比值、CD4总计数、淋巴细胞总计数）的变化及与疗效的相关性。

Objectives of Study：

1. Primary Objective To evaluate the objective response rate (ORR) of SBRT combined with Apalizumab Tolvareli and chemotherapy in recurrent/oligometastatic pancreatic cancer; 2. Secondary Objectives (1) To evaluate the disease control rate (DCR) of SBRT combined with Apalizumab Tolvareli and chemotherapy in recurrent/oligometastatic pancreatic cancer; (2) To evaluate the duration of response (DOR) of SBRT combined with Apalizumab Tolvareli and chemotherapy in recurrent/oligometastatic pancreatic cancer; (3) To evaluate the progression-free survival (PFS) of SBRT combined with Apalizumab Tolvareli and chemotherapy in recurrent/oligometastatic pancreatic cancer; (4) To evaluate the overall survival (OS) of SBRT combined with Apalizumab Tolvareli and chemotherapy in recurrent/oligometastatic pancreatic cancer; (5) To evaluate the safety and tolerability of SBRT combined with Apalizumab Tolvareli and chemotherapy, including the incidence of serious adverse events (SAE) and immune-related adverse events (irAE), and the incidence of treatment discontinuation due to SAE/irAE; (6) To explore changes in biomarkers in peripheral blood samples collected continuously before and after SBRT (including but not limited to CD8/Treg ratio, total CD4 counts, total lymphocyte counts) and their correlation with efficacy.

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.经组织学或细胞学确认的胰腺导管腺癌（包括腺鳞癌）； 
2.复发胰腺癌或晚期胰腺癌伴寡转移患者；
3.至少一次全身治疗（包括化疗、免疫治疗或靶向治疗）期间或之后出现进展； 
4.距离末次全身治疗（包括化疗、免疫治疗或靶向治疗）>=1月； 
5.无放疗史，或二次放疗部位与原放疗部位无重叠； 
6.签署书面知情同意书并理解且同意遵循研究要求和研究访视安排表； 
7.签署知情同意书时>=18岁且<=80岁的男性或女性受试者； 
8.美国东部肿瘤协作组（ECOG）体能状态评分（PS）为0或1； 
9.根据RECIST v1.1标准至少存在1个靶病灶，基线时经计算机断层扫描（CT）或磁共振成像（MRI）（首选静脉注射造影剂）准确测量显示其长直径≥10 mm（淋巴结除外，淋巴结的短轴必须>=15 mm），且病灶适合反复准确测量。位于既往接受过放射照射区域或接受过活检的病灶，如果明确证明出现符合RECIST v1.1标准的疾病进展，则该病灶可作为可测量靶病灶。
10.预期生存时间>=3月； 
11.具有充分的骨髓和器官功能（接受实验室检查前14天内未使用任何细胞、血液成分、集落刺激因子及细胞因子治疗）： 
(1)血常规：ANC>=1.5×10^9/L或正常范围内；血小板计数（platelet，PLT）>=100×10^9/L；血红蛋白（hemoglobin，HGB）>=90 g/L； 
(2)肝功能：总胆红素（total bilirubin，TBIL）<=1.5×ULN；如果为Gilbert综合征受试者，TBIL<=3×ULN；对于无肝转移的受试者，AST和ALT<=2.5×ULN；对于存在肝转移的受试者，AST和ALT<=5×ULN；白蛋白（albumin，ALB）>=28 g/L； 
(3)肾功能：血清肌酐（Cr）<=1.5×ULN，或肌酐清除率（creatinine clearance rate，CCR）>=60 mL/min（使用Cockcroft-Gault公式计算或测量24小时尿液采集量计算）；尿常规提示尿蛋白＜2+，对基线时尿常规检测显示尿蛋白>=2+的受试者，应进行24小时尿液采集且24小时内尿液中的蛋白含量＜1g（如果两种检测方法都被采用，则将使用24小时尿液采集测得的数值用于确定资格）； 
(4)凝血功能：国际标准化比值（international normalized ratio，INR）<=1.5；活化部分凝血活酶时间（activated partial thromboplastin time，APTT）<=1.5×ULN； 
12.无生育能力或同意在研究期间（从筛选或首次给药前14天开始，以先发生者为准，持续至研究药物末次给药后180天）使用至少1种高效避孕方法的男性和女性受试者；

Inclusion criteria

1. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (including adenosquamous carcinoma);
2. Patients with recurrent pancreatic cancer or advanced pancreatic cancer with oligometastases;
3. Disease progression occurring during or after at least one systemic treatment (including chemotherapy, immunotherapy, or targeted therapy);
4. At least one month since the last systemic treatment (including chemotherapy, immunotherapy, or targeted therapy);
5. No history of radiotherapy, or if undergoing second radiotherapy, the site does not overlap with the original radiotherapy site;
6. Signed written informed consent and understanding and agreement to comply with study requirements and the study visit schedule;
7. Male or female subjects aged >= 18 years and <=80 years at the time of signing the informed consent;
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1;
9. At least one measurable lesion according to RECIST v1.1, with baseline measurement by computed tomography (CT) or magnetic resonance imaging (MRI) (preferably with intravenous contrast), showing a longest diameter of >=10 mm (excluding lymph nodes, lymph nodes must have a short axis >=15 mm), and the lesion is suitable for repeated accurate measurement. Lesions located in areas that have previously received radiation or biopsy can be considered measurable target lesions if there is clear evidence of disease progression according to RECIST v1.1;
10. Expected survival time >=3 months;
11. Sufficient bone marrow and organ function (no use of any cellular therapy, blood components, colony-stimulating factors, or cytokine treatment within 14 days prior to laboratory tests):
(1) Complete blood count: ANC >= 1.5×10^9/L or within normal range; platelet count (PLT) >= 100×10^9/L; hemoglobin (HGB) >= 90 g/L;
(2) Liver function: total bilirubin (TBIL) <= 1.5×ULN; for subjects with Gilbert's syndrome, TBIL <= 3×ULN; for subjects without liver metastases, AST and ALT <= 2.5×ULN; for subjects with liver metastases, AST and ALT <= 5×ULN; albumin (ALB) >= 28 g/L;
(3) Kidney function: serum creatinine (Cr) <= 1.5×ULN, or creatinine clearance rate (CCR) >= 60 mL/min (calculated using the Cockcroft-Gault formula or measured by 24-hour urine collection); urinalysis shows urine protein <2; for subjects whose baseline urinalysis shows urine protein >=2, a 24-hour urine collection should be conducted with urine protein content <1g within 24 hours (if both methods are used, the value measured from the 24-hour urine collection will be used to determine eligibility);
(4) Coagulation function: international normalized ratio (INR) <= 1.5; activated partial thromboplastin time (APTT) <= 1.5×ULN.
12. Male and female subjects who are infertile or agree to use at least one effective method of contraception during the study (from 14 days prior to screening or first dosing, whichever occurs first, and continuing until 180 days after the last dose of the study drug).

排除标准：

1.对抗PD-1/CTLA-4抗体的任何成分有过敏史; 2.广泛弥漫转移（转移器官>3个或转移灶>5个）; 3.已知存在活动性脑转移或脑膜转移者; 4.肝转移病灶占总肝体积的50%以上者。 5.预期生存数据<3月; 6.无法平躺或无法在放疗过程中保持平躺10–20分钟者; 7.未控制的心脏临床症状或疾病，包括： (1)纽约心脏协会（NYHA）II级或以上心力衰竭。 (2)不稳定型心绞痛。 (3)过去一年内内出现心肌梗死。 (4)需要临床干预的临床意义重大的室上性或室性心律失常。 8.既往治疗，包括： (1)在研究药物首次给药前1月内使用过任何试验药物。 (2)同时参与另一项临床试验，除非它是观察性（非干预性）临床研究。 (3)在研究药物首次给药前2周内需要全身性皮质类固醇治疗（>=10毫克泼尼松等效剂量/天）或其他免疫抑制剂的患者，但局部炎症和过敏、恶心和呕吐的预防除外。其他特殊情况应与研究者讨论。在没有活动性自身免疫性疾病的情况下，允许使用吸入式或局部应用的皮质类固醇和等效于>10毫克/天泼尼松的肾上腺皮质激素替代剂量。 (4)在研究药物首次给药前4周内接受过抗肿瘤疫苗或活疫苗的患者。 (5)在研究药物首次给药前4周内接受过重大手术或遭受过严重创伤的患者。 9.根据不良事件通用术语标准（CTCAE），未从前一次抗肿瘤治疗中恢复到≤1级（脱发和与先前铂类治疗相关的神经病变后遗症除外），或不符合纳入/排除标准中规定的水平。 10.在研究药物首次给药前4周内经历过严重感染（CTCAE等级>2），包括严重肺炎、菌血症、需要住院治疗的并发症感染、基线胸部影像学检查上存在活动性肺部炎症、研究药物首次给药前4周内的感染症状和体征，或需要口服或静脉抗生素治疗。 11.活动性自身免疫性疾病或自身免疫性疾病史（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、甲状腺功能减退，包括但不限于这些疾病或综合征）。然而，接受稳定剂量甲状腺激素替代治疗的自身免疫性甲状腺功能减退症患者和接受稳定剂量胰岛素治疗的I型糖尿病患者不被排除。患有白癜风或儿童期哮喘/过敏但在成年期无需干预即可缓解的患者也有资格参加。 12.免疫缺陷史，包括HIV检测阳性、获得性或先天性免疫缺陷疾病史，或器官移植和同种异体骨髓移植史。 13.间质性肺病（不包括未经类固醇治疗的放射性肺炎）或非感染性肺炎病史。 14.根据病史或CT扫描证据显示活动性结核感染，入组前1年内有活动性结核感染，或过去1年以上有活动性结核感染史但未接受正规治疗。 15.乙型肝炎活动期患者（HBV DNA>=500 IU/mL或2500拷贝/mL）或丙型肝炎活动期患者（抗HCV阳性且HCV-RNA高于检测下限）。 16.有物质滥用、酒精滥用或药物成瘾史。 17.孕妇或哺乳期妇女。 18.研究者认为有其他可能导致研究提前终止的因素的受试者，如患有需要同时治疗的其他严重疾病（包括精神疾病）、实验室值显著异常、可能影响受试者安全或数据收集的家庭或社会因素等。

Exclusion criteria：

1. History of allergy to any component of PD-1/CTLA-4 antibodies; 2. Extensive diffuse metastasis (more than 3 metastatic organs or more than 5 metastatic lesions); 3. Known active brain metastases or meningeal metastases; 4. Liver metastases accounting for more than 50% of total liver volume; 5. Expected survival data < 3 months; 6. Unable to lie flat or unable to maintain a flat position for 10–20 minutes during radiotherapy; 7. Uncontrolled cardiac clinical symptoms or diseases, including: (1) New York Heart Association (NYHA) class II or above heart failure; (2) Unstable angina; (3) Myocardial infarction within the past year; (4) Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention. 8. Prior treatments, including: (1) Use of any investigational drug within 1 month before the first administration of the study drug. (2) Simultaneous participation in another clinical trial, unless it is an observational (non-interventional) clinical study. (3) Patients requiring systemic corticosteroid therapy (≥10 mg prednisone equivalent/day) or other immunosuppressants within 2 weeks before the first administration of the study drug, except for local inflammation and allergy, prevention of nausea and vomiting. Other special cases should be discussed with the investigator. In the absence of active autoimmune disease, the use of inhaled or locally applied corticosteroids and adrenal corticosteroid replacement doses greater than 10 mg/day prednisone equivalent is allowed. (4) Patients who have received anti-tumor vaccines or live vaccines within 4 weeks before the first administration of the study drug. (5) Patients who have undergone major surgery or suffered serious trauma within 4 weeks before the first administration of the study drug. 9. Have not recovered to <= grade 1 (except for alopecia and sequelae of neuropathy related to previous platinum therapy) from previous anti-tumor treatment according to the Common Terminology Criteria for Adverse Events (CTCAE), or do not meet the levels specified in the inclusion/exclusion criteria. 10. Experienced severe infection (CTCAE grade >2) within 4 weeks before the first administration of the study drug, including severe pneumonia, bacteremia, complication infections requiring hospitalization, active pulmonary inflammation on baseline chest imaging, infection symptoms and signs within 4 weeks before the first administration of the study drug, or requiring oral or intravenous antibiotic treatment. 11. Active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes). However, patients with autoimmune hypothyroidism receiving a stable dose of thyroid hormone replacement therapy and patients with type 1 diabetes receiving a stable dose of insulin are not excluded. Patients with vitiligo or childhood asthma/allergies that resolve in adulthood without intervention are also eligible to participate. 12. History of immunodeficiency, including HIV positive test, history of acquired or congenital immunodeficiency disorders, or history of organ transplantation and allogeneic bone marrow transplantation. 13. Interstitial lung disease (excluding radiation pneumonitis not treated with steroids) or history of non-infectious pneumonia. 14. Evidence of active tuberculosis infection based on medical history or CT scan, active tuberculosis within 1 year before enrollment, or history of active tuberculosis more than 1 year ago without receiving standard treatment. 15. Patients with active hepatitis B (HBV DNA >= 500 IU/mL or 2500 copies/mL) or active hepatitis C (anti-HCV positive and HCV-RNA above the detection limit). 16. History of substance abuse, alcohol abuse, or drug addiction. 17. Pregnant or breastfeeding women. 18. Subjects whom the researcher believes have other factors that may lead to early termination of the study, such as having other serious diseases that require concurrent treatment (including mental illnesses), significant abnormalities in laboratory values, or family or social factors that may affect the subject's safety or data collection, etc.

研究实施时间：

Study execute time：

从 From 2025-10-01 00:00:00至 To 2027-10-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-11-12 00:00:00 至 To 2027-10-01 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	39
Group：	Experimental group	Sample size：	39
干预措施：	SBRT联合艾帕洛利托沃瑞利单抗和化疗	干预措施代码：
Intervention：	SBRT Combined with a PD-1/CTLA-4 Bispecific Antibody and Chemotherapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	浙江大学医学院附属第二医院	单位级别：	三级甲等
Institution hospital：	The second affiliated hospital of Zhejiang University school of medicine	Level of the institution：	Tertiary A

测量指标：

Outcomes：

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：	SBRT后12个月	测量方法：
Measure time point of outcome：	12 months after SBRT	Measure method：

指标中文名：	客观缓解率（ORR）	指标类型：	主要指标
Outcome：	Objective response rate	Type：	Primary indicator
测量时间点：	SBRT后3个月	测量方法：
Measure time point of outcome：	3 months after SBRT	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：	SBRT后3个月	测量方法：
Measure time point of outcome：	3 months after SBRT	Measure method：

指标中文名：	无进展生存期	指标类型：	次要指标
Outcome：	Progression free survival	Type：	Secondary indicator
测量时间点：	SBRT后1年	测量方法：
Measure time point of outcome：	12 months after SBRT	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	其它	说明
Fate of sample：	0thers	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	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：	无
Blinding：	None

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）：	邮件联系研究者
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Contact the researcher by email
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：	CRF
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：	2026-04-13 15:51:23