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：	ChiCTR2600123934
最近更新日期： Date of Last Refreshed on：	2026-05-01 21:09:36
注册时间： Date of Registration：	2026-05-01 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	免疫靶向治疗联合溶瘤HSV病毒用于可手术切除头颈鳞癌新辅助治疗的前瞻性、单臂临床研究
Public title：	A Prospective, Single-arm Clinical Study of Immune-targeted Therapy Combined With Lysogenic HSV Virus for the Neoadjuvant Treatment of Surgically Resectable Head and Neck Squamous Carcinoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	免疫靶向治疗联合溶瘤HSV病毒用于可手术切除头颈鳞癌新辅助治疗的前瞻性、单臂临床研究
Scientific title：	A Prospective, Single-arm Clinical Study of Immune-targeted Therapy Combined With Lysogenic HSV Virus for the Neoadjuvant Treatment of Surgically Resectable Head and Neck Squamous 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：	闵宇	研究负责人：	彭星辰
Applicant：	Min Yu	Study leader：	Peng Xingchen
申请注册联系人电话： Applicant telephone：	+86 131 0817 5138	研究负责人电话： Study leader's telephone：	+86 28 8542 1141
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：	13108175138@163.com	研究负责人电子邮件： Study leader's E-mail：	pxx2014@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：	中国四川省成都市武侯区国学巷37号	研究负责人通讯地址：	中国四川省成都市武侯区国学巷37号
Applicant address：	37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China	Study leader's address：	37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China
申请注册联系人邮政编码： Applicant postcode：	610041	研究负责人邮政编码： Study leader's postcode：	610041
申请人所在单位：	四川大学华西医院
Applicant's institution：	West China Hospital of Sichuan University
研究负责人所在单位：	四川大学华西医院
Affiliation of the Leader：	West China Hospital of Sichuan 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：	2024 年审 (2497) 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：	四川大学华西医院生物医学伦理审查委员会
Name of the ethic committee：	Biomedical Ethics Review Committee of West China Hospital of Sichuan University
伦理委员会批准日期： Date of approved by ethic committee：	2025-02-19 00:00:00
伦理委员会联系人：	邓邵林
Contact Name of the ethic committee：	Deng Shaolin
伦理委员会联系地址：	中国四川省成都市武侯区国学巷37号
Contact Address of the ethic committee：	37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 28 8542 1141	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：

四川大学华西医院

Primary sponsor：

West China Hospital of Sichuan University

研究实施负责（组长）单位地址：

中国四川省成都市武侯区国学巷37号

Primary sponsor's address：

37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 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)：	四川	市(区县)：	成都
Country：	China	Province：	Sichuan	City：	Chengdu
单位(医院)：	四川大学华西医院	具体地址：	四川省成都市武侯区国学巷37号
Institution hospital：	West China Hospital of Sichuan University	Address：	No. 37, Guoxue Lane, Wuhou District, Chengdu City, Sichuan Province

经费或物资来源：

临床研究孵化项目

Source(s) of funding：

Clinical Research Incubation Project

研究疾病：

头颈鳞癌

Target disease：

head and neck 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：

对可手术切除的头颈部鳞状细胞癌患者采用免疫靶向疗法联合亚临床型单纯疱疹病毒新辅助疗法的安全性和耐受性的评估。

Objectives of Study：

Evaluation of the safety and tolerability of immune-targeted therapy combined with neoadjuvant therapy with lysogenic HSV virus for patients with surgically resectable squamous carcinoma of the head and neck.

药物成份或治疗方案详述：

采取“3+3”实验设计，剂量递增阶段组1先入组3例受试者。如果3例受试者均没有出现DLT，可递增至下一个剂量组。如果3例受试者中>=2例出现DLT，则终止剂量递增。如果3例受试者中有1例出现DLT，则该剂量组需要再入组3例，以完成该剂量的耐受性观察：当新入组的3例受试者均未再出现DLT，则可递增至下一剂量组；如新入组的受试者仍有>=1例出现DLT，则终止剂量递增，且该剂量被认为是不可耐受剂量（见表1）。Ia期试验确定最大耐受剂量后，额外招募3名受试者进入Ib期固定剂量试验，受试者采用Ia期确定的最大耐受剂量进行溶瘤HSV病毒注射以进一步评估治疗疗效

Description for medicine or protocol of treatment in detail：

A "3+3" design was adopted for the dose-escalation phase, with Cohort 1 initially enrolling 3 subjects. If none of the 3 subjects experienced dose-limiting toxicity (DLT), escalation to the next dose level was permitted. If >=2 of the 3 subjects experienced DLT, dose escalation was terminated. If 1 of the 3 subjects experienced DLT, an additional 3 subjects were enrolled at that dose level to complete tolerability assessment: if none of the newly enrolled 3 subjects experienced DLT, escalation to the next dose level was permitted; if >=1 of the newly enrolled subjects experienced DLT, dose escalation was terminated, and that dose was considered intolerable (see Table 1). After determining the maximum tolerated dose (MTD) in Phase Ia, an additional 3 subjects were recruited for the Phase Ib fixed-dose trial, receiving oncolytic HSV virus injection at the MTD determined in Phase Ia to further evaluate therapeutic efficacy.

纳入标准：

Inclusion criteria

1. Age >=18 and <=70 years old, regardless of gender

2. Patients with head and neck squamous carcinoma who are pathologically confirmed and fulfill the following conditions: Patients with locally advanced head and neck squamous carcinoma (excluding nasopharyngeal, salivary gland and thyroid malignant tumors) who are initially diagnosed and have no distant metastasis

3. Non oropharyngeal HNSCC carcinoma and HPV-negative oropharyngeal carcinoma, stages III, IVA and IVB

4. HPV-positive oropharyngeal cancers, stages II and III

5. HPV status of oropharyngeal cancer will be determined by p16 immunohistochemistry. Treatable by surgical resection as evaluated by head and neck surgery

6. Definite lymph node metastasis and lymph node stage is not N0 or Nx. An Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1

7. Have adequate organ and bone marrow function as defined below: Subjects voluntarily enrolled in the study, signed an informed consent form, and were able to comply with the visits and related procedures specified in the protocol.

排除标准：

1. 淋巴结分期为N0或者Nx状态； 2. 其它恶性肿瘤病史（已治愈的且5年内未复发的皮肤基底细胞癌、皮肤鳞状细胞癌、浅表性膀胱癌、原位宫颈癌、胃肠道粘膜内癌等研究者认为可以入组的恶性肿瘤史除外）； 3. 任何活动性自身免疫病或有自身免疫病病史，包括但不限于与免疫有关的神经疾病、多发性硬化症、自身免疫性（脱髓鞘）神经病、格林巴利综合症、重症肌无力、系统性红斑狼疮（SLE）、结缔组织疾病、硬皮病、炎症性肠病包括克罗恩病和溃疡性结肠炎、自身免疫性肝炎、中毒性表皮坏死松解症（TEN）或Stevens-Johnson综合征（使用稳定剂量的胰岛素的Ⅰ型糖尿病除外）； 4. 有过敏性疾病、严重药物过敏史、已知对大分子蛋白制剂、PD-1单抗注射液或阿法替尼处方中任何组分过敏者（注：严重过敏指导致住院）； 5. 接受过以下任何治疗： (1) 既往使用过PD-1抗体、PD-L1抗体、CTLA-4抗体、EGFR抗体或EGFR-TKI的患者； (2) 接种过抗肿瘤疫苗者； (3) 首次给药前4周内或计划在研究期间内使用任何抗感染性疾病的活性疫苗（如流感疫苗，水痘疫苗等）； (4) 首次给药前4周内接受过大手术或有严重外伤； 6. 在服用研究药物前14天内需要使用皮质类固醇（>10 毫克/天的泼尼松）或其他免疫抑制剂进行全身治疗的患者，允许吸入或局部使用类固醇和肾上腺激素（>10 毫克/天的泼尼松）作为替代疗法； 7. 伴有严重的内科疾病者，如Ⅱ级及以上心功能异常（NYHA 标准）、缺血性心脏病（如心肌梗死或心绞痛）、有临床意义的室上性或室性心律失常，超声心动图显示射血分数<50%；QTc间期，男性>450 msec，女性>470 msec；心电图检查异常且研究者认为对试验药物有额外风险； 8. 已知间质性肺炎病史、非感染性肺炎病史或高度怀疑有间质性肺炎的受试者；或可能会干扰可疑的药物相关肺毒性的检测或处理的受试者；允许既往曾有药源性或放射性非感染性肺炎但无症状的受试者入组；有活动性肺结核，或既往有肺结核感染史但经治疗未控制者； 9. 甲状腺功能亢进症的患者和患有器质性甲状腺疾病的患者不能入组，用稳定剂量的甲状腺替代激素治疗的甲状腺功能减退症可以入组，用甲状腺替代激素治疗可以控制的甲状腺功能减退症可以入组（是否可以控制由研究者和/或内分泌科确认）； 10. 存在活动性感染，或者在筛选期间、首次给药前48 h发生原因不明的发热，或者签署知情同意前1周内使用全身性抗生素； 11. 存在活动性乙型肝炎（HBV DNA>=2000 IU/ml或10^4拷贝数/ml）或丙型肝炎（丙肝抗体阳性，且HCV RNA高于分析方法的检测下限），或已知有人类免疫缺陷病毒（HIV）检查阳性病史或已知有获得性免疫缺陷综合征（艾滋病）； 12. 既往有明确的神经或精神障碍史，如癫痫或痴呆； 13. 有明确药物滥用史或3个月内有酒精滥用史； 14. 妊娠期或者哺乳期妇女；受试者（及其伴侣）在筛选期至其研究结束后3个月内有生育计划，无避孕措施的性行为，或不愿采取适当的避孕措施（如采用避孕套、避孕环或伴侣结扎等）； 15. 首次使用研究药物前4周内接受过任何研究性药物，或同时入组另外一项临床研究，除非是观察性（非干预性）临床研究或者干预性临床研究随访； 16. 研究者判断受试者可能存在影响本研究的其他因素，导致无法完成试验用药及随访。

Exclusion criteria：

1. Lymph node staging of N0 or Nx status; 2. History of other malignancies (except history of cured and non-recurrent basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical cancer in situ, intramucosal carcinoma of the gastrointestinal tract, and other malignancies considered by the investigator to be eligible for enrollment); 3. Any active autoimmune disease or history of autoimmune disease including, but not limited to, immune-related neurological disorders, multiple sclerosis, autoimmune (demyelinating) neuropathies, Guillain-Barre Syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal Necrolytic Elastosis (TEN) or Stevens-Johnson Syndrome (except for type I diabetes on stabilized doses of insulin); 4. A history of anaphylaxis, severe drug allergy, known allergy to any component of a large protein preparation, PD-1 monoclonal antibody injection, or afatinib prescription (Note: severe allergy is defined as resulting in hospitalization); 5. Received any of the following treatments: (1) Patients with prior use of PD-1 antibody, PD-L1 antibody, CTLA-4 antibody, EGFR antibody, or EGFR-TKI; (2) Patients who have received an anti-tumor vaccine; (3) Use of any active vaccine against infectious diseases (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to the first dose or scheduled to be used during the study period; (4) Major surgery or severe trauma within 4 weeks prior to the first dose of study drug; 6. Inhaled or topical steroids and adrenal hormones (>10 mg/day of prednisone) are permitted as an alternative therapy for patients requiring systemic therapy with corticosteroids (>10 mg/day of prednisone) or other immunosuppressive agents within 14 days prior to administration of study drug; 7. Those with serious medical conditions such as abnormal class II or higher cardiac function (NYHA criteria), ischemic heart disease (e.g., myocardial infarction or angina pectoris), clinically significant supraventricular or ventricular arrhythmia with echocardiographic ejection fraction <50%; QTc interval, >450 msec in men and >470 msec in women; and an abnormal electrocardiogram that, in the opinion of the investigator, poses an experimental drug There is an additional risk; 8. Subjects with a known history of interstitial pneumonia, history of non-infectious pneumonia, or a high suspicion of interstitial pneumonia; or subjects who may interfere with the detection or management of suspected drug-related pulmonary toxicity; subjects with a prior history of pharmacogenetic or radiologic non-infectious pneumonia that is asymptomatic are permitted to enroll in the study; subjects with active tuberculosis, or with a history of prior tuberculosis infection that has not been controlled with treatment; 9. Patients with hyperthyroidism and patients with organic thyroid disease are not eligible for enrollment; hypothyroidism treated with a stable dose of thyroid replacement hormone is eligible for enrollment, and hypothyroidism that can be controlled with thyroid replacement hormone treatment is eligible for enrollment (control or not will be confirmed by the investigator and/or the endocrinology department); 10. Presence of an active infection, or fever of unknown origin during screening, 48 h prior to the first dose, or use of systemic antibiotics within 1 week prior to signing informed consent; 11. Presence of active hepatitis B (HBV DNA >= 2000 IU/ml or 10^4 copies/ml) or hepatitis C (hepatitis C antibody positive with HCV RNA above the lower limit of detection of the analytical method), or known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS); 12. A previous history of a definite neurologic or psychiatric disorder, such as epilepsy or dementia; 13. A definite history of substance abuse or a history of alcohol abuse within 3 months; 14. Women who are pregnant or breastfeeding; subjects (and their partners) who have plans to have children, have sex without contraception, or are unwilling to use adequate contraception (e.g., use of condoms, contraceptive rings, or partner sterilization) during the screening period to 3 months after the end of their study; 15. Received any investigational drug within 4 weeks prior to the first dose of study drug or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up; 16. In the judgment of the investigator, the subject may have other factors affecting this study that would prevent completion of the trial medication and follow-up.

研究实施时间：

Study execute time：

从 From 2026-05-01 00:00:00至 To 2027-12-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-05-01 00:00:00 至 To 2027-12-30 00:00:00

干预措施：

Interventions：

组别：	剂量递增阶段 1 组	样本量：	3
Group：	Dose Escalation Phase 1 Group	Sample size：	3
干预措施：	溶瘤 HSV 病毒 10^6 pfu/mL，1-4ml，注射2次，每剂间隔2周	干预措施代码：
Intervention：	Oncolytic HSV virus 10^6 pfu/mL, 1-4 mL, injected twice with a 2-week interval between doses	Intervention code：

组别：	剂量递增阶段 2 组	样本量：	3
Group：	Dose Escalation Phase 2 Group	Sample size：	3
干预措施：	溶瘤 HSV 病毒 10^8 pfu/mL，1-4ml，注射2次，每剂间隔2周	干预措施代码：
Intervention：	Oncolytic HSV virus 10^8 pfu/mL, 1-4 mL, injected twice with a 2-week interval between doses	Intervention code：

组别：	Ib期固定剂量组	样本量：	3
Group：	Phase Ib Fixed Dose Group	Sample size：	3
干预措施：	替雷利珠单抗 200mg，每周第1天静脉滴注，每3周为1个给药周期，共给药2次；马来酸阿法替尼片 30mg，口服，每天1次，连续口服6周；溶瘤 HSV 病毒（采用Ia期确定的最大耐受剂量，每患者注射2次，每剂间隔2周，具体剂量根据淋巴结大小决定：直径<=1.5cm注射1ml，1.5-2.5cm注射2ml，>2.5cm注射4ml）	干预措施代码：
Intervention：	Tislelizumab 200 mg, intravenous infusion on day 1 of each week, every 3 weeks for 2 cycles; Afatinib maleate tablets 30 mg, oral, once daily for 6 consecutive weeks; Oncolytic HSV virus (maximum tolerated dose determined in Phase Ia, injected twice per patient with a 2-week interval between doses, with dosage determined by lymph node size: 1 mL for diameter <=1.5 cm, 2 mL for 1.5–2.5 cm, 4 mL for >2.5 cm)	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	四川	市(区县)：
Country：	China	Province：	Sichuan	City：
单位(医院)：	四川大学华西医院	单位级别：	三甲
Institution hospital：	West China Hospital of Sichuan University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	剂量限制性毒性（DLT）发生率	指标类型：	主要指标
Outcome：	Incidence of Dose-Limiting Toxicity (DLT)	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：	次要指标
Outcome：	Major Pathological Response Rate (MPR)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	病理完全缓解率	指标类型：	次要指标
Outcome：	Pathological Complete Response Rate (pCR)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	首次确认完全缓解（CR）、部分缓解（PR）的时间（Time to first response）	指标类型：	次要指标
Outcome：	The Time to first response for the first confirmation of complete response (CR) and partial response (PR)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	治疗有效持续时间	指标类型：	次要指标
Outcome：	Duration of Response (DOR)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	首次确认疾病稳定持续时间	指标类型：	次要指标
Outcome：	Time to First Confirmed 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：	无进展生存时间	指标类型：	次要指标
Outcome：	Progression-Free Survival (PFS)	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 (OS)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	生存质量（QOL）	指标类型：	次要指标
Outcome：	Quality of Life (QOL)	Type：	Secondary indicator
测量时间点：		测量方法：	EORTC QLQ-C30 问卷
Measure time point of outcome：		Measure method：	EORTC QLQ-C30 questionnaire

指标中文名：	安全性指标（包括：不良事件（AE）、严重不良事件（SAE）、剂量限制性毒性（DLT）、生命体征、体格检查、实验室检查（血常规、血生化、尿常规、凝血功能、甲状腺功能、心肌酶谱、BNP、淋巴细胞亚群等）、心电图、影像学检查（头颈部 MRI/CT、胸部 CT、腹部 CT/MRI、骨扫描）	指标类型：	副作用指标
Outcome：	Safety Outcomes (including Adverse Events (AE), Serious Adverse Events (SAE), Dose-Limiting Toxicity (DLT), Vital Signs, Physical Examination, Laboratory Tests (hematology, chemistry, urinalysis, coagulation, thyroid function, cardiac enzymes, BNP, lymphocyte subsets), Electrocardiogram, Imaging Studies (MRI/CT of head and neck, chest CT, abdominal CT/MRI, bone scan))	Type：	Adverse events
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：	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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	70	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：	无
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	None
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2026-05-01 21:09:29