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：	ChiCTR1900025796
最近更新日期： Date of Last Refreshed on：	2019-09-08 23:04:29
注册时间： Date of Registration：	2019-09-08 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	免疫化疗（化疗+特瑞普利）联合大分割放疗治疗不可切除复发/转移性头颈部鳞癌
Public title：	Chemotherapy plus Toripalimab Augmented by Hypofractionated Radiotherapy as First Line Treatment for Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
注册题目简写：
English Acronym：
研究课题的正式科学名称：	免疫化疗（化疗+特瑞普利）联合大分割放疗治疗不可切除复发/转移性头颈部鳞癌的前瞻性、单臂、单中心临床研究
Scientific title：	A prospective, one-arm, single-center clinical study for chemotherapy plus Toripalimab augmented by hypofractionated radiotherapy as first line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)
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：	邹枕玮	研究负责人：	杨坤禹
Applicant：	Zhenwei Zou	Study leader：	Kunyu Yang
申请注册联系人电话： Applicant telephone：	+86 13437262475	研究负责人电话： Study leader's telephone：	+86 13995595360
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：	zouzhenwei1983@126.com	研究负责人电子邮件： Study leader's E-mail：	yangky71@aliyun.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：	湖北省武汉市江汉区邬家墩156号	研究负责人通讯地址：	湖北省武汉市江汉区邬家墩156号
Applicant address：	156 Wujiadun, Jianghan District, Wuhan, Hubei	Study leader's address：	156 Wujiadun, Jianghan District, Wuhan, Hubei
申请注册联系人邮政编码： Applicant postcode：	430022	研究负责人邮政编码： Study leader's postcode：	430022
申请人所在单位：	华中科技大学同济医学院附属协和医院肿瘤中心
Applicant's institution：	Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
研究负责人所在单位：	华中科技大学同济医学院附属协和医院肿瘤中心
Affiliation of the Leader：	Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

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：	2019-S1068	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：	华中科技大学同济医学院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology
伦理委员会批准日期： Date of approved by ethic committee：	2019-07-24 00:00:00
伦理委员会联系人：	陈汇
Contact Name of the ethic committee：	Chen Hui
伦理委员会联系地址：	武汉市硚口区汉口航空路13号
Contact Address of the ethic committee：	13 Hankou Aviation Road, Qiaokou District, Wuhan, Hubei
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：

华中科技大学同济医学院附属协和医院肿瘤中心

Primary sponsor：

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

研究实施负责（组长）单位地址：

湖北省武汉市江汉区邬家墩156号

Primary sponsor's address：

156 Wujiadun, Jianghan District, Wuhan, Hubei

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	湖北	市(区县)：	武汉市
Country：	China	Province：	Hubei	City：	Wuhan
单位(医院)：	华中科技大学同济医学院附属协和医院	具体地址：	解放大道1277号
Institution hospital：	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Address：	1277 Jiefang Avenue

经费或物资来源：

上海君实生物医药科技股份有限公司

Source(s) of funding：

Shanghai Junshi Biopharmaceutical Technology Co., Ltd.

研究疾病：

复发/转移头颈部鳞癌

Target disease：

Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck

研究疾病代码：

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

探索性研究/预试验

Study phase：

0

研究设计：

单臂

Study design：

Single arm

研究目的：

初步评价在免疫化疗（化疗/特瑞普利）基础上进一步联合大分割放疗治疗不可切除复发/转移头颈部鳞癌的安全性和有效性。

Objectives of Study：

This study aims to investigate efficacy, safety and tolerability of taxane-based chemotherapy plus Toripalimab augmented by hypofractionated radiotherapy (8Gy*3F) as first Line treatment for patients with recurrent/ metastatic head and neck squamous cell carcinoma (HNSCC).

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. 18 to 65 years of age, regardless of sex.
2. Histologically- or cytologically-confirmed recurrent/ metastatic head and neck squamous cell carcinoma (oropharynx, oral cavity, hypopharynx, or larynx), as well as patients with distant metastasis at first diagnosis, considered incurable by local treatment.
3. No prior systemic therapy administered in the recurrent/ metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease).
4. Exist at least one meatastatic or primary tumor could receive hypofractionated radiotherapy.
5. All cases must have measurable disease as defined in RECIST 1.1 excluding radiotherapy lesions.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Demonstrate adequate organ function as defined below, with all screening labs to be obtained within 28 days prior to registration
(1) blood routine examination criteria should be met (no blood transfusion or blood products within 14 days):
a) Hemoglobin (Hgb) >= 9 g/dL
b) Absolute Neutrophil Count (ANC) >= 1.5 K/mm3
c) Platelets >= 80 K/mm3
(2) biochemical examination shall meet the following criteria:
a) Bilirubin <= 1.25 × upper limit of normal (ULN)
b) Aspartate aminotransferase (AST) <= 2.5 × ULN or < 5x ULN if the transferase elevation was due to liver metastases 
c) Alanine aminotransferase (ALT) <= 2.5 × ULN or <5x ULN if the transferase elevation was due to liver metastases
d) Calculated Creatinine Clearance <= ULN or >= 50 cc/min using the Cockcroft-Gault formula
8. Can provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable. HPV status must be done for oropharyngeal cancer.
9. Sign a written informed consent form prior to the conduct of any pilot-related activities,
10. Able to comply with the research plan judged by the researcher,
11. Pregnancy test negative at screening (for women with fertility)
12. Fertile men and women at risk of fertility and pregnancy must agree to use two methods of birth control throughout the study period (at least one of which is considered to be efficient). Female patients who are not fertile (that is, at least one of the following criteria is met): 
-hysterectomy and / or bilateral ovariectomy and documented records; 
-the decline of ovarian function, which has been confirmed by medicine; 
-in the postmenopausal state, defined as at least 12 months of continuous menopause without other pathological or physiological reasons, and the status confirmed by serum follicle-stimulating hormone (FSH) levels is consistent with the postmenopausal state. 
13. There is a signed and dated informed consent indicating that the patient (or legitimate representative, if permitted by the local guide / practice specification) has been informed of all relevant aspects of the study.
14. Must have read, understood, and provided written informed consent voluntarily. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

排除标准：

1. 适用于局部治疗并可行根治性治疗的复发/转移性鳞癌；
2. 根治性治疗后6个月内复发/转移的患者；
3. 正在参加其他临床试验及药物治疗；
4. 预期寿命<3个月及/或患有进展迅速的疾病；
5. 除经治疗的皮肤基底细胞癌、皮肤鳞状细胞癌和/或经治疗的原位宫颈癌和/或乳腺癌外，在入组前5年内诊断和/或治疗其他恶性肿瘤；
6. 既往接受过抗 PD-1、抗 PD-L1、抗 PD-L2、抗 CD137 或抗 CTLA-4 抗体（包括伊匹木单抗）或特别靶向作用于 T 细胞共同刺激或免疫检查点通路的任何其他抗体或药物的免疫治疗；
7. 入组前 ≤4 周接受过重大手术；
8. 已证实对PD-1抗体或其辅料过敏者；
9．任何活动性自身免疫病或有自身免疫病病史（如，间质性肺炎、葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、心肌炎、肾炎、甲状腺功能亢进、甲状腺功能降低（激素替代治疗有效后可纳入）等：患有白癜风或在童年期哮喘已完全缓解，成人后无需任何干预、需要支气管扩张剂进行医学干预的哮喘患者可纳入）；
10. 未能控制的心脏临床症状或疾病，如：（1） NYHA II级以上心力衰竭（2）不稳定型心纹痛（3）1年内发生过心肌梗死（4）有临床意义的室上性或室性心律失常需要临床干预的患者；
11. 给予研究药物前14天内，要求使用皮质类固醇（＞10mg/天泼尼松疗效剂量）或其他免疫抑制剂进行系统治疗的受试者，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＞10mg/天泼尼松疗效剂量的肾上腺激素替代；
12. 需要治疗的活动性感染；
13. 患有先天或后天免疫功能缺陷（如HIV感染者）、活动性乙肝（ HBV-DNA≥104（拷贝数／ml或2000IU／ml）或丙肝（丙肝抗体阳性，且 HCV－RNA高于分析方法的检测下限）；
14. 开始研究治疗前4周内接种过活疫苗；
15. 已知有精神类药物滥用、酗酒或吸毒史；
16. 妊娠期或哺乳期妇女；
17. 经研究者判断，受试者有其他可能导致其被迫中途终止研究的因素，如患有其他严重疾病（含精神疾病）需要合并治疗，实验室检查值严重异常，家庭或社会因素，可能影响到受试者安全或试验资料收集的情况；
18. 研究登记后2个月内，MRI记录有未经治疗/活跃的脑转移的患者；
19. 活动性肺结核；
20. 开始研究治疗前4周内发生的严重感染（包括但不限于因感染、菌血症或重症肺炎并发症而住院治疗）；
21. 在开始研究治疗前4周内接受过全身免疫刺激药物治疗（包括但不限于干扰素或白介素－2）或仍在5个药物半衰期内（取二者中较长者）。

Exclusion criteria：

1. Disease suitable for local therapy administered with a curative intent.
2. Progressive disease (PD) within six months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
3. Participating in other clinical trials and drug treatments
4. Life expectancy of < 3 months and/or has rapidly progressing disease.
5. Diagnosed and/or treated additional malignancy within 5 years with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers.
6. Previous immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibodies (including ipilimumab) or any other antibodies or drugs specifically targeting T cell co-stimulation or immune checkpoint pathway.
7. Received major surgery within 4 weeks prior to randomization.
8. Known allergy to PD-1 antibody, or any ingredient;
9. Any active autoimmune disease or a history of autoimmune disease (e.g., Interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, Decreased thyroid function (hormone replacement therapy can be included after effective), etc.: suffering from vitiligo or complete remission of asthma in childhood, Asthma patients who do not need any intervention in adults and need medical intervention with bronchodilators can be included).
10. Uncontrolled clinical symptoms or diseases of the heart, Such as: (1) heart failure above NYHA II grade;(2) unstable heart pain;(3) myocardial infarction within 1 year;(4) patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
11. Within 14 days before administration of the study drug, subjects who were required to be treated systematically with corticosteroids (> 10mg/d prednisone) or other immunosuppressants, in the absence of active autoimmune disease, Inhaled or local use of steroids and dosage > 10mg/ prednisone therapeutic dose of adrenocortical hormone replacement are allowed.
12. Active infection requiring systemic therapy.
13. Congenital or acquired immune deficiency (such as HIV infection), active hepatitis B (HBV-DNA >= 10K(copy number/ml or 2000IU/ml) or hepatitis C (positive for hepatitis C antibody, and HCV-RNA is higher than the detection limit of the analytical method).
14. Vaccinated with live vaccine within 4 weeks before the start of the study.
15. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
16. Pregnant or lactating women.
17. According to the researchers, the subjects had other factors that might have forced them to terminate the study, such as the need for combined treatment for other serious diseases, including mental illness, severe abnormalities in laboratory tests, and family or social factors that may affect the safety of the subjects or the collection of experimental data.
18. Active central nervous system metastases and/or carcinomatous meningitis.
19. Active pulmonary tuberculosis.
20. Severe infections that occurred within 4 weeks prior to the start of the study (including, but not limited to, hospitalization due to infection, bacteremia or complications of severe pneumonia).
21. Treated with systemic immunostimulating drugs (including, but not limited to, interferon or IL-2) within 4 weeks before the start of the study, or still within the five half-life of drugs (Take the longer of the two).

研究实施时间：

Study execute time：

从 From 2019-09-01 00:00:00至 To 2022-09-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2019-09-01 00:00:00 至 To 2020-08-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	36
Group：	Treatment Group	Sample size：	36
干预措施：	免疫化疗+大分割放疗	干预措施代码：
Intervention：	Chemotherapy plus Toripalimab Augmented by Hypofractionated Radiotherapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	湖北	市(区县)：
Country：	China	Province：	Hubei	City：
单位(医院)：	华中科技大学同济医学院附属协和医院	单位级别：	三级甲等
Institution hospital：	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	不良事件	指标类型：	主要指标
Outcome：	Adverse Events	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（ORR）	指标类型：	主要指标
Outcome：	Objective remission rate (ORR)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	1年无进展生存率	指标类型：	主要指标
Outcome：	Progression-free survival (PFS) rate at 1 year	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	1年总生存率	指标类型：	次要指标
Outcome：	Overall Survival rate at 1 year	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	2年总生存率	指标类型：	次要指标
Outcome：	Overall Survival rate at 2 year	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：	病理组织	组织：
Sample Name：	pathological tissue	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

标本中文名：	血液	组织：
Sample Name：	blood	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：

正在进行

Recruiting

年龄范围：

Participant age：

最小 Min age		岁 years
最大 Max age		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）：

不适用

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

Not applicable

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：	N/A
Blinding：	N/A
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	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）：	Not stated
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Not stated
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：	病历记录表
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Case Record Form, CRF
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2019-09-08 23:04:29