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：	ChiCTR2100043743
最近更新日期： Date of Last Refreshed on：	2021-06-26 13:18:07
注册时间： Date of Registration：	2021-02-27 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	PD-1单抗联合吉西他滨加顺铂新辅助化疗治疗可切除的局部晚期头颈鳞状细胞癌的有效性与安全性的Ib期临床研究
Public title：	The efficacy and safety of PD-1 monoclonal antibody plus neoadjuvant chemotherapy with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma: a phase Ib clinical trial
注册题目简写：
English Acronym：
研究课题的正式科学名称：	PD-1单抗联合吉西他滨加顺铂新辅助化疗治疗可切除的局部晚期头颈鳞状细胞癌的有效性与安全性的Ib期临床研究
Scientific title：	The efficacy and safety of PD-1 monoclonal antibody plus neoadjuvant chemotherapy with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma: a phase Ib clinical trial
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：	刘志刚	研究负责人：	刘志刚
Applicant：	Zhigang Liu	Study leader：	Zhigang Liu
申请注册联系人电话： Applicant telephone：	+86 18627585860	研究负责人电话： Study leader's telephone：	+86 18627585860
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：	zhigangliu@hotmail.com	研究负责人电子邮件： Study leader's E-mail：	zhigangliu@hotmail.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：	广东省珠海市香洲区梅华东路52号	研究负责人通讯地址：	广东省珠海市香洲区梅华东路52号
Applicant address：	52 Meihua Road East, Xiangzhou District, Zhuhai, Guangdong, China	Study leader's address：	52 Meihua Road East, Xiangzhou District, Zhuhai, Guangdong, 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：	中山大学附属第五医院
Applicant's institution：	The Fifth Affiliated Hospital of Sun Yat-Sen University
研究负责人所在单位：	中山大学附属第五医院
Affiliation of the Leader：	The Fifth Affiliated Hospital of Sun Yat-Sen 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：	中大五院【2020】伦字第（K66-1)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：	中山大学附属第五医院伦理委员会
Name of the ethic committee：	Ethics Committee of the Fifth Affiliated Hospital of Sun Yat-Sen University
伦理委员会批准日期： Date of approved by ethic committee：	2020-09-24 00:00:00
伦理委员会联系人：	傅雪婷
Contact Name of the ethic committee：	Xueting Fu
伦理委员会联系地址：	广东省珠海市香洲区梅华东路52号
Contact Address of the ethic committee：	52 Meihua Road East, Xiangzhou District, Zhuhai, Guangdong, China
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：

中山大学附属第五医院

Primary sponsor：

The Fifth Affiliated Hospital of Sun Yat-Sen University

研究实施负责（组长）单位地址：

广东省珠海市香洲区梅华东路52号

Primary sponsor's address：

52 Meihua Road East, Xiangzhou District, Zhuhai, Guangdong, 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	市(区县)：	珠海
Country：	China	Province：	Guangdong	City：	Zhuhai
单位(医院)：	中山大学附属第五医院	具体地址：	梅华东路52号
Institution hospital：	The Fifth Affiliated Hospital of Sun Yat-Sen University	Address：	52 Meihua Road East, Xiangzhou District

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 Biomedical Technology Co., Ltd

研究疾病：

头颈部鳞癌

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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

1、评估PD-1单抗联合新辅助化疗治疗的安全性，包括不良事件( PD-1单抗首次给药后90天内或术后30天内)，手术无延迟率。 2、观察PD-1单抗联合新辅助化疗和手术治疗后的有效性：包括病理完全缓解率（pCR）、主要病理缓解率（MPR），客观缓解率（ORR）； 3年总生存率（OS）和无疾病生存（PFS）率。

Objectives of Study：

1.To evaluate the safety of PD-1 mAb combined with neoadjuvant chemotherapy, including adverse events (within 90 days after initial administration of PD-1 mAb or within 30 days after surgery), and no delay rate of surgery. 2.To observe the efficacy of PD-1 monoclonal antibody combined with neoadjuvant chemotherapy and surgery: pathological complete response rate (PCR), major pathological response rate (MPR), objective response rate (ORR);3-year overall survival (OS) and disease-free survival (PFS) rates.

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. Untreated patients with locally advanced squamous cell carcinoma of the head and neck confirmed by histology or cytology;
2. Patients judged by surgeons to be operable;
3. Patients aged from 18 to 70 years old;
ECoG: 0-2 points;
5. Patients with an estimated survival time of more than 6 months;
6. According to RECIST 1.1, subjects with at least one measurable lesion;
7. The functions of main organs meet the following standards (no blood components or cell growth factors are allowed to be used within 14 days)
(1) HB >= 90 g / L; Neutrophil ANC >= 1.5 x 109 /L Platelet count PLT >= 100 x 10^9 /L
(2) Serum albumin >= 28g / L;
(3) TBIL <= 1.5 x ULN (upper limit of normal value), alt, AST <= 2.5 x ULN If there is liver metastasis, ALT and AST <= 5 x ULN
(4) Serum creatinine <= 1.5 x ULN and creatinine clearance rate >= 50 ml / min;
(5) Activated partial thromboplastin time (APTT) and international normalized ratio (INR) <= 1.5 x ULN (for anticoagulant therapy with stable dose, such as low molecular weight heparin or warfarin, and INR can be selected within the expected treatment range of anticoagulant);
(6) TSH <= ULN; If the level of T3 and T4 is abnormal, the patients with normal level of T3 and T4 can be selected;
8. Women of childbearing age should agree to use contraceptive measures (such as intrauterine device, contraceptive or condom) during and within 3 months after medication; The patients with negative serum or urine pregnancy test within 7 days before the study, who must be non lactation patients, and men should agree to use contraceptives during the study period and within 3 months after the end of the study period;
9. The subjects voluntarily joined the study, signed informed consent, good compliance, and cooperated with the follow-up.

排除标准：

1.怀孕或哺乳期妇女；
2.既往对PD-1单抗或吉西他滨、顺铂中任何药物有过敏史；
3.既往5年内或同时患其它恶性肿瘤病史，但已治愈的皮肤基底细胞癌和宫颈原位癌以及甲状腺乳头癌等除外；
4.未能控制的心脏临床症状或疾病，如：（1）NYHAⅡ级以上心力衰竭（2）不稳定型心绞痛（3）1年内发生过心肌梗死（4）有临床意义上的室上性或者室性心律失常需要临床干预的患者；
5.接受过以下的任何治疗：
a.首次使用研究药物前接受过任何研究性药物；
b.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；
c.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每天泼尼松疗效剂量的肾上腺皮质激素替代；
d.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；
e. 首次使用研究药物前4周内接受过大手术或者严重外伤；
f.心脏左室射血分数大于等于60%；
6.首次使用研究药物前4周内发生过严重感染（CTC AE大于2级），如需要住院的严重肺炎、菌血症、感染合并症等；基线胸部影像学检查提示存在活动性肺部炎症、首次使用研究药物前2周内存在感染的症状和体征或需要口服或静脉使用抗生素治疗（不包括预防性使用抗生素的情况）；
7.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；
8.有免疫缺陷病史，包括HIV检测阳性，或患有其他获得性、先天性免疫缺陷疾病，或有器官移植史和骨髓移植史；
9.通过病史或者CT检查发现有活动性肺结核感染，或入组前1年内有活动性肺结核感染病史的患者，或查过1年以前有活动性肺结核感染病史但未经正规治疗的患者；
10.受试者存在活动性肝炎（HBV DNA≥2000IU/ml 或者10；000 copies/ml），丙型肝炎（丙肝抗体阳性，且HCV-RNA高于分析方法的检测下限）
11.已知有精神类药物的滥用、酗酒及吸毒史；
12.有症状的脑转移者(已经证实或怀疑)；
13.研究者认为不适合纳入者。

Exclusion criteria：

1. Pregnant or lactating women;
2. Patients who had a history of allergy to PD-1 mAb, gemcitabine or cisplatin;
3. Patients with a history of other malignant tumors in the past 5 years or at the same time, except the cured basal cell carcinoma of the skin, carcinoma in situ of the cervix and papillary carcinoma of the thyroid;
4. Patients with uncontrollable cardiac clinical symptoms or diseases, such as:
(1) Heart failure above NYHA grade II;
(2) Unstable angina pectoris;
(3) Myocardial infarction occurred within 1 year;
(4) Patients with clinical supraventricular or ventricular arrhythmias requiring clinical intervention;
5. Subjects who have received any of the following treatments:
(1) Received any research drug before the first use of the research drug;
(2) At the same time, another clinical study was enrolled, unless it was an observational (non intervention) clinical study or a follow-up intervention of a new clinical study;
(3) Subjects requiring systemic treatment with corticosteroids (more than 10 mg prednisone equivalent dose per day) or other immunosuppressants within 2 weeks before the first use of the study drug, except for the use of corticosteroids for local inflammation and prevention of allergy, nausea and vomiting. In the absence of active autoimmune diseases, inhaled or topical corticosteroids and corticosteroids with a dose greater than 10 mg prednisone per day are allowed;
(4) Had been vaccinated with anti-tumor vaccine or had been vaccinated with live vaccine within 4 weeks before the first administration of the research drug;
(5) Major surgery or severe trauma within 4 weeks before the first use of the study drug;
(6) Left ventricular ejection fraction (LVEF) was more than or equal to 60%;
6. Subjects with severe infection (CTC AE greater than grade 2) within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, infection complications, etc; Baseline chest imaging revealed active pulmonary inflammation, symptoms and signs of infection within 2 weeks before the first use of the study drug, or the need for oral or intravenous antibiotics (excluding prophylactic use of antibiotics);
7. Patients with active autoimmune diseases or autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes); Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone; Use stable insulin in type 1 diabetes. It does not include patients with vitiligo or recovered childhood asthma / allergy who do not need any intervention in adulthood;
8. Patients with history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or history of organ transplantation or bone marrow transplantation;
9. Subjects with active pulmonary tuberculosis infection found by medical history or CT examination, or patients with active pulmonary tuberculosis infection history within 1 year before enrollment, or patients with active pulmonary tuberculosis infection history 1 year before enrollment but without regular treatment;
10. Active hepatitis (HBV DNA >= 2000 IU / ml or 10; 000 copies / ml), hepatitis C (HCV antibody positive and HCV-RNA higher than the detection limit of the analytical method)
11. Known history of psychotropic drug abuse, alcoholism and drug abuse;
12. Patients with symptomatic brain metastases (confirmed or suspected);
13. Subjects considered unsuitable by the researchers.

研究实施时间：

Study execute time：

从 From 2020-09-01 00:00:00至 To 2021-03-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2021-02-25 00:00:00 至 To 2021-06-01 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	20
Group：	Experimental group	Sample size：	20
干预措施：	三程吉西他滨+顺铂+特瑞普利单抗新辅助治疗	干预措施代码：
Intervention：	Three cycles of PD-1 monoclonal antibody plus neoadjuvant chemotherapy with gemcitabine and cisplatin	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	广东	市(区县)：	珠海
Country：	China	Province：	Guangdong	City：	Zhuhai
单位(医院)：	中山大学附属第五医院	单位级别：	三级甲等
Institution hospital：	The Fifth Affiliated Hospital of Sun Yat sen University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	完全病理缓解率	指标类型：	主要指标
Outcome：	pathologic complete response, pCR	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	主要病理缓解率	指标类型：	主要指标
Outcome：	Major pathological response, MMR	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：	主要指标
Outcome：	Objective Response 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：	R0切除率	指标类型：	主要指标
Outcome：	complete resection	Type：	Primary 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：	N/A	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	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）：

未使用

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

Not used

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）：	待定请阅读网页注册指南中关于共享原始数据的内容。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	To be determined
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：	病例报告表
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Case report form
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：	2021-02-27 10:33:33