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：	ChiCTR2400085098
最近更新日期： Date of Last Refreshed on：	2024-05-30 21:46:56
注册时间： Date of Registration：	2024-05-30 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	干扰素α联合特瑞普利单抗用于二线治疗铂类耐药的复发/转移或局部晚期不可手术的头颈鳞癌患者的单臂、Ⅱ期临床研究
Public title：	A single-arm,phase ll clinical study of interferon alpha combined with toripalimab for second-line treatment of platinum-resistant recurrent/metastatic or locally advanced inoperable head and neck squamous cell carcinoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	干扰素α联合特瑞普利单抗用于二线治疗铂类耐药的复发/转移或局部晚期不可手术的头颈鳞癌患者的单臂、Ⅱ期临床研究
Scientific title：	A single-arm,phase ll clinical study of interferon alpha combined with toripalimab for second-line treatment of platinum-resistant recurrent/metastatic or locally advanced inoperable head and neck 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：	杨文艺	研究负责人：	胡镜宙
Applicant：	Wenyi Yang	Study leader：	Jingzhou Hu
申请注册联系人电话： Applicant telephone：	+86 158 0193 3121	研究负责人电话： Study leader's telephone：	+86 158 2117 5891
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：	yangwenyi2018@163.com	研究负责人电子邮件： Study leader's E-mail：	huyayi@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：	上海市黄浦区制造局路833弄12号	研究负责人通讯地址：	上海市黄浦区制造局路833弄12号
Applicant address：	No.12, Lane 833, Zhizaoju Road, Huangpu District, Shanghai	Study leader's address：	No.12, Lane 833, Zhizaoju Road, Huangpu District, Shanghai
申请注册联系人邮政编码： Applicant postcode：	200023	研究负责人邮政编码： Study leader's postcode：	200023
申请人所在单位：	上海交通大学医学院附属第九人民医院
Applicant's institution：	Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
研究负责人所在单位：	上海交通大学医学院附属第九人民医院
Affiliation of the Leader：	Ninth People's Hospital Affiliated to Shanghai Jiao Tong 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：	SH9H-2023-T438-2	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：	上海交通大学医学院附属第九人民医院医学伦理委员会
Name of the ethic committee：	shanghai Ninth People's Hospital, ShanghaiJiao Tong University School of Medicine Ethics Committec
伦理委员会批准日期： Date of approved by ethic committee：	2024-03-01 00:00:00
伦理委员会联系人：	刘墨池
Contact Name of the ethic committee：	Mochi Liu
伦理委员会联系地址：	上海交通大学医学院附属第九人民医院
Contact Address of the ethic committee：	Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 130 2322 5213	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：

上海交通大学医学院附属第九人民医院

Primary sponsor：

Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

研究实施负责（组长）单位地址：

上海市黄浦区制造局路639号

Primary sponsor's address：

No.639, Zhizaoju Road, Huangpu District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	上海市	市(区县)：
Country：	CHINA	Province：	shanghai	City：
单位(医院)：	上海交通大学医学院附属第九人民医院	具体地址：	上海市黄浦区制造局路639号
Institution hospital：	Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Address：	No.639, Zhizaoju Road, Huangpu District, Shanghai

经费或物资来源：

上海交通大学医学院附属第九人民医院

Source(s) of funding：

Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

研究疾病：

头颈部鳞状细胞癌

Target disease：

head and neck squamous cell carcinoma

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期临床试验

Study phase：

2

研究设计：

单臂

Study design：

Single arm

研究目的：

评价入组患者中使用特瑞普利单抗联合干扰素α二线治疗铂类耐药的复发/转移或局部晚期不可手术的头颈鳞癌患者的有效性，是否能提高患者的客观缓解率(ORR)。

Objectives of Study：

To evaluate the efficacy of toripalimab combined with interferon alpha in second-line treatment of platinum-resistant recurrent/metastatic or locally advanced inoperable head and neck squamous cell carcinoma in enrolled patients, and whether it can improve the objective response rate of patients.

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

a) Age 18-75 years old, male or female;
b) Patients with head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, and larynx) with a measurable lesion (spiral CT ≥10mm, meeting RECIST 1.1 criteria) confirmed by histopathology as recurrent/metastatic or locally advanced and inoperable after surgery;
c) Tumor progression within 6 months after first-line treatment involving platinum-based chemotherapy;
d) Tumor tissues for detection of PD-L1, RIG-I, and lncMX1-215 (paraffin specimens or fresh tumor tissues within 2 years) can be provided;
e) ECOG score of 0 or 1;
f) Expected survival ≥12 weeks;
g) Major organ function is normal within 2 weeks prior to treatment, that is, the following criteria are met:
• Bone marrow function: hemoglobin ≥100g/L, white cell count ≥4.0*10^9/L or neutrophil count ≥2.0*10^9/L, platelet count ≥100*10^9/L without blood transfusion or colony-stimulating factor support therapy;
• Liver: serum total bilirubin level ≤1.5 times the normal upper limit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times the normal upper limit;
• Kidney: blood creatinine level below 1.5 times the normal upper limit or creatinine clearance ≥60ml/min, urea nitrogen ≤200mg/L;
• Urine protein <+, if urine protein +, 24-hour total protein must be <500mg;
• Blood sugar: In the normal range and/or in patients with diabetes who are under treatment but whose blood sugar is controlled in a stable state;
• Lung function: baseline FEV1 of at least 2L; If the baseline FEV1 is <2L, the postoperative FEV1 is estimated to be >800ml by the surgical expert.
• Heart function: no myocardial infarction within 1 year; Unstable angina pectoris; No symptomatic severe arrhythmia; Acardiac dysfunction;
h) Women of childbearing age must have a negative serum pregnancy test result within 7 days before the first administration of the test drug; Fertile men or women with the possibility of becoming pregnant must use highly effective contraceptive methods (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) throughout the trial and continue contraception for 3 months after the end of treatment;
i) The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with the follow-up;
j) Patients whom doctors believe will benefit from treatment.(YNMT)·

排除标准：

a) 既往接受过抗PD-1、抗PD-L1、抗PD-L2治疗的患者； b) 既往接受过干扰素α治疗的患者； c) 目前正接受抗肿瘤治疗的患者； d) 研究首次用药前4周内进行/接受了大型外科手术或尚未从此手术的副作用中恢复、2周内进行了放疗、活疫苗接种、免疫治疗； e) 研究药物首次用药前4周内参加或正在参加其他药物/疗法临床试验的患者。 f) 入组前6个月内接受过头颈部位（包括颈部、锁骨上以及锁骨下淋巴结）的再次放疗； g) 具有肿瘤包绕、侵犯或浸润大血管，侵及皮肤或粘膜腔，或者肿瘤病灶出现破溃出血； h) 经影像学诊断，存在活动性或不可控制的转移性中枢神经系统肿瘤病灶； i) 5年内有其他恶性肿瘤病史，但已治愈的皮肤基底细胞癌、皮肤鳞癌、早期前列腺癌和宫颈原位癌除外； j) 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）； k) 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），并在入组前2周内仍在继续使用的； l) 研究药物首次给药前1周内曾接受造血刺激因子,如接受粒细胞集落刺激因子(G-CSF)、促红细胞生成素等治疗的患者； m) HIV抗体或梅毒螺旋体抗体检测结果阳性； n) 活动性乙型肝炎或丙型肝炎患者: 如HBsAg或HBcAb阳性,加测HBV DNA(测定结果高于正常值范围上限)；如HCV抗体检测结果阳性,加测HCV RNA(测定结果高于正常值范围上限)； o) 已知会对干扰素α制品、重组人源化PD-1单克隆抗体药物及其组分过敏者； p) 伴有临床症状且需要对症处理的大量胸水或腹水； q) 活动性肺部疾病(间质性肺炎、肺炎、阻塞性肺病、哮喘)或有活动性肺结核病史； r) 具有任何无法控制的临床问题,包括但不限于: 持续性或活动性(严重)感染; 控制不佳的糖尿病; 心脏疾病(纽约心脏学会定义的III/IV级充血性心力衰竭或心脏传导阻滞); 药物控制不良的高血压(血压持续大于150/90mmHg)；首次用药前6个月内出现过如下情况: 深静脉血栓或肺栓塞；心肌梗死;严重或不稳定性心律失常或心绞痛；经皮冠状动脉介入治疗、急性冠脉综合征、冠状动脉旁路移植术；脑血管意外、短暂性脑缺血发作、脑栓塞。 s) 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； t) 随机前3个月内出现过显著临床意义的出血症状或具有明确的出血倾向，如日咳/咯血2.5ml及以上、消化道出血、有出血危险的食管胃底静脉曲张、出血性胃溃疡或患有脉管炎等，基线期若大便潜血阳性，可复查，复查后若仍为阳性，需要进行胃镜检查，若胃镜提示重度食管胃底静脉曲张则不能入组（入组前3个月及以内接受胃镜检查排除此类情况者除外）； u) 已知存在的遗传性或获得性出血及血栓倾向（如血友病人，凝血机能障碍，血小板减少等）； v) 曾接受过干细胞移植或器官移植。 w) 具有精神类药物滥用史且无法戒除者或有精神障碍史者。 x) 癫痫和其他中枢神经系统功能紊乱者; y) 研究者判断可能会增加参加研究相关的风险、或者可能干扰研究结果的解释的其它重度、急性或慢性医学疾病或实验室检查异常。 z) 研究者判断依从性不佳,或有其他情况导致不适合参加本试验的患者

Exclusion criteria：

a) Patients who have previously received anti-PD-1, anti-PD-L1, anti-PD-L2 therapy; b) Patients who have previously received interferon alpha therapy; c) Patients currently receiving antitumor therapy; d) Major surgery had been performed or had not recovered from the side effects of surgery within 4 weeks prior to the first dose, radiotherapy, live vaccination, and immunotherapy within 2 weeks; e) Patients who have participated in or are participating in clinical trials of other drugs/therapies within 4 weeks prior to the first administration of the investigational drug. f) Received reradiotherapy to the head and neck area (including neck, supraclavicular, and subclavian lymph nodes) within 6 months before enrollment; g) tumors surrounding, invading or infiltrating large blood vessels, invading the skin or mucous cavity, or the tumor lesions appear ruptured bleeding; h) Active or uncontrollable metastatic central nervous system tumors diagnosed by imaging; i) a history of other malignancies within 5 years, with the exception of cured skin basal cell carcinoma, skin squamous cell carcinoma, early prostate cancer, and cervical carcinoma in situ; j) The patient has any active autoimmune disease or a history of autoimmune disease (e.g., but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism; The patient had vitiligo; Those with complete remission of asthma in childhood can be included without any intervention in adulthood; Patients with asthma requiring medical intervention with bronchodilators are not included); k) Patients who are taking immunosuppressants or systemic hormone therapy for immunosuppressive purposes (dose >10mg/ day prednisone or other therapeutic hormone) and continue to use within 2 weeks prior to enrollment; l) Study patients who had received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc., within 1 week prior to initial drug administration; m) Positive HIV antibody or treponema pallidum antibody test result; n) Patients with active hepatitis B or C: if HBsAg or HBcAb positive, add HBV DNA test (test results above the upper limit of the normal range); If the HCV antibody test is positive, add HCV RNA(the test result is higher than the upper limit of the normal range); o) those who are known to be allergic to interferon alpha products, recombinant humanized PD-1 monoclonal antibody drugs and their components; p) A large amount of pleural fluid or ascites accompanied by clinical symptoms requiring symptomatic management; q) a history of active lung disease (interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma) or active pulmonary tuberculosis; r) Have any clinical problems that cannot be controlled, including but not limited to: persistent or active (serious) infection; Poorly controlled diabetes; Heart disease (Grade III/IV congestive heart failure or heart block as defined by the Heart Society of New York); Poorly controlled hypertension (persistent blood pressure greater than 150/90 MMHG); Deep vein thrombosis or pulmonary embolism occurred within 6 months before the first dose; Myocardial infarction; Severe or unstable arrhythmia or angina; Percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; Cerebrovascular accident, transient ischemic attack, cerebral embolism. s) Abnormal coagulation function (INR>2.0, PT>16s), bleeding tendency or receiving thrombolytic or anticoagulant therapy, allowing prophylactic use of low-dose aspirin or low-molecular weight heparin; t) Clinically significant bleeding symptoms or definite bleeding tendency occurred within 3 months before randomization, such as day cough/hemoptysis of 2.5ml or more, digestive tract bleeding, esophageal varices with bleeding risk, hemorrhagic gastric ulcer or vasculitis, etc., if stool was positive for occult blood at baseline, it could be re-examined; if stool was still positive after re-examination, gastroscopy should be performed. If gastroscopy showed severe esophageal and fundus varices, they could not be included in the group (except those who were excluded by gastroscopy within 3 months before enrollment). u) known hereditary or acquired bleeding and thrombotic tendencies (e.g. hemophiliacs, coagulation disorders, thrombocytopenia, etc.); v) Have received a stem cell transplant or an organ transplant. w) Those who have a history of psychotropic substance abuse and are unable to abstain or have a history of mental disorders. x) epilepsy and other central nervous system disorders; y) other severe, acute, or chronic medical conditions or abnormalities in laboratory tests that the investigator determines may increase the risk associated with study participation or may interfere with the interpretation of the study results. z) Patients who are judged by the investigator to have poor compliance or other conditions that make them ineligible to participate in this trial

研究实施时间：

Study execute time：

从 From 2024-06-01 00:00:00至 To 2026-05-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-06-01 00:00:00 至 To 2025-05-31 00:00:00

干预措施：

Interventions：

组别：	治疗组	样本量：	20
Group：	Treatment Group	Sample size：	20
干预措施：	1、特瑞普利单抗静脉滴注给药（无需预防用药），固定剂量240mg，针对基线期体重<50kg的受试者，采用3mg/kg。每次输注30 min（不少于20 min，不超过60 min），3周给药1次，每21天为1个周期，累计最长用药时间为2年； 2、干扰素α采用300μg/次，隔日皮下注射，3周为一个治疗周期。	干预措施代码：
Intervention：	1. Toripalimab was administered intravenously (no prophylaxis required) at a fixed dose of 240mg, 3mg/kg for subjects with body weight <50kg at baseline. Each infusion is 30 min (not less than 20 min, not more than 60 min), and the drug is given once every 3 weeks, every 21 days is a cycle, and the maximum cumulative duration of drug use is 2 years; 2. Interferon alpha was injected subcutaneously at 300μg/ time every other day for a treatment cycle of 3 weeks.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海市	市(区县)：	上海市
Country：	China	Province：	Shanghai	City：	Shanghai
单位(医院)：	上海交通大学医学院附属第九人民医院	单位级别：	三甲
Institution hospital：	Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Level of the institution：	top three hospitals

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：

指标中文名：	总生存期	指标类型：	主要指标
Outcome：	overall 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：	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：	部分缓解	指标类型：	次要指标
Outcome：	partial response	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	完全缓解	指标类型：	次要指标
Outcome：	complete response	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	疾病稳定	指标类型：	次要指标
Outcome：	stable disease	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	疾病进展	指标类型：	次要指标
Outcome：	progressive disease	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：	肿瘤组织	组织：
Sample Name：	tumor tissue	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation 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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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：	1）病例报告表每个参与临床研究的受试者都应记录其完整的eCRF。除君实公司或监管当局授权的代表外，未经君实公司书面许可，一律不准以任何形式提供给第三方。研究者需对记录在eCRF和其他数据收集表（原始记录）中的所有临床，安全和实验室数据的收集和报告负最终责任，以确保该记录的可归因性、易读性、及时性、原始性、准确性、持久性、完整性和一致性。 eCRF必须获得研究者或相关授权人的签名确认，以证实eCRF中记录的数据是真实的。在eCRF和原始记录中的任何数据修正，都必须注明日期，签署姓名，并给予必要的解释，但不可掩盖先前的原始记录。一般情况下，原始记录是医院或医生的图表。此时，eCRF中收集的数据必须与这些图表的数据保持一致。而在某些情况下，eCRF也可作为原始记录。此时，研究机构需要有相关文档，以明确那些数据将记录在eCRF中，并将eCRF作为原始记录。 2）试验记录的保存为满足监管当局或君实的审核和/或稽查要求，研究者/机构需同意保存相关记录，包括所有参与受试者的身份识别号（足够的信息链接到记录中，如eCRF和医院的记录），所有原始签署的知情同意书，所有eCRF副本，安全报告表，原始记录，治疗处理的细节记录，相关沟通文档（如信件，会议记录，电话报告）。研究者/机构需按照相关规范要求保存记录。研究者/机构若有任何原因不能继续保存研究记录时，应预先通知君实公司，研究记录需转移给君实公司指定的接受人，或君实公司安排的独立第三方。即使保留期满后，研究者在处理本研究的任何记录时，也必须获得君实公司的书面许可。当资料无需继续保存时，君实公司将及时通知研究者/机构。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	1) Case report form Every subject participating in a clinical study should record their complete eCRF. Except for the representatives authorized by the Junshi company or the regulatory authorities, it is not allowed to be provided to third parties in any form without the written permission of the company. The investigator is ultimately responsible for the collection and reporting of all clinical, safety and laboratory data recorded in the eCRF and other data collection forms (original records) to ensure that the records are attributable, legible, timely, original, accurate, persistent, complete, and consistent. The eCRF must obtain a signature confirmation from the investigator or relevant authorized person to confirm that the data recorded in the eCRF is authentic. Any data correction in the eCRF and the original record must be dated, signed, and given the necessary explanation, but the previous original record must not be obscured. In general, the original records are hospital or doctor's charts. At this point, the data collected in the eCRF must be consistent with the data in these charts. In some cases, the eCRF can also serve as the original record. At this point, the research institution needs to have documentation to clarify which data will be recorded in the eCRF, and to use the eCRF as the original record. 2) Preservation of test records In order to meet regulatory and/or audit requirements, the investigator/institution agrees to maintain relevant records, including identification numbers of all participating subjects (sufficient information linked to the records, such as eCRF and hospital records), all original signed informed consent forms, all copies of eCRF, safety report forms, original records, and other relevant information. Records of the details of the treatment, relevant communication documents (e.g. letters, minutes of meetings, telephone reports). Researchers/institutions are required to maintain records in accordance with relevant regulatory requirements. If, for any reason, the investigator/institution is unable to continue to maintain the research record, it shall notify the Company in advance that the research record shall be transferred to the recipient designated by the Company or to an independent third party arranged by the company. Even after the retention period has expired, the investigator must obtain written permission from Junshi to process any records of this study. When the data no longer need to be stored, the company will inform the researcher/institution in a timely manner.
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：	2024-05-30 21:46:50