ChiCTR2500109818 版本V1.0 版本创建时间2025/09/25 11:33:21 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2500109818 

最近更新日期：

Date of Last Refreshed on：

2025-09-25 11:33:15 

注册时间：

Date of Registration：

2025-09-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

新辅助免疫联合质子放疗治疗局晚期鼻咽癌研究

Public title：

Study on the Treatment of Advanced Nasopharyngeal Carcinoma with neoadjuvant immunotherapy combined with Proton radiotherapy

注册题目简写：

English Acronym：

研究课题的正式科学名称：

新辅助免疫联合质子放疗治疗局晚期鼻咽癌研究

Scientific title：

Study on the Treatment of Advanced Nasopharyngeal Carcinoma with neoadjuvant immunotherapy combined with Proton radiotherapy

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：

高劲 

研究负责人：

高劲 

Applicant：

Jin Gao 

Study leader：

Jin Gao 

申请注册联系人电话：

Applicant telephone：

+86 551 6532 0585

研究负责人电话：

Study leader's telephone：

+86 551 6532 0585

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：

gj11667@126.com

研究负责人电子邮件：

Study leader's E-mail：

gj11667@126.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：

安徽省合肥市蜀山区环湖东路107号

研究负责人通讯地址：

安徽省合肥市蜀山区环湖东路107号

Applicant address：

No. 107 Huanhu East Road, Shushan District, Hefei City, Anhui Province

Study leader's address：

No. 107 Huanhu East Road, Shushan District, Hefei City, Anhui 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：

安徽省肿瘤医院

Applicant's institution：

Anhui Provincial Cancer Hospital

研究负责人所在单位：

安徽省肿瘤医院

Affiliation of the Leader：

Anhui Provincial Cancer Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2025-LLYJ-0029

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：

安徽省肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Anhui Provincial Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2025-06-16 00:00:00

伦理委员会联系人：

王欣晨

Contact Name of the ethic committee：

Xinchen Wang

伦理委员会联系地址：

安徽省合肥市蜀山区环湖东路107号

Contact Address of the ethic committee：

No. 107 Huanhu East Road, Shushan District, Hefei City, Anhui Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 139 5515 6771

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：

安徽省肿瘤医院

Primary sponsor：

Anhui Provincial Cancer Hospital

研究实施负责（组长）单位地址：

安徽省合肥市蜀山区环湖东路107号

Primary sponsor's address：

No. 107 Huanhu East Road, Shushan District, Hefei City, Anhui 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)：

安徽

市(区县)：

合肥市

Country：

China

Province：

Anhui

City：

Hefei

单位(医院)：

安徽省肿瘤医院

具体地址：

安徽省合肥市蜀山区环湖东路107号

Institution
hospital：

Anhui Provincial Cancer Hospital

Address：

No. 107 Huanhu East Road, Shushan District, Hefei City, Anhui Province

经费或物资来源：

自筹经费

Source(s) of funding：

Self-raised funds

Target disease：

Nasopharyngeal carcinoma

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：

本研究旨在评估新辅助信迪利单抗联合化疗序贯调强质子放疗（IMPT）联合化疗治疗局晚期鼻咽癌的疗效和安全性，探索免疫与质子放疗的最佳结合模式，建立鼻咽癌治疗高效低毒的新方案。  

Objectives of Study：

The aim of this study is to evaluate the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy and sequential intensity-modulated proton therapy (IMPT) combined with chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma, explore the optimal combination mode of immunotherapy and proton therapy, and establish a new highly efficient and low toxicity treatment plan for nasopharyngeal carcinoma.

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. 在实施任何试验相关流程之前，签署书面知情同意； 2. 性别不限，年龄18-70岁； 3. 经组织学或细胞学确定，研究者评估为未经任何治疗的III-IVA期（除T3-4N0、T3N1）局晚期鼻咽癌； 4. ECOG PS评分为0-1； 5. 根据实体肿瘤疗效评价标准（RECIST 1.1版），至少有一处影像学可测量病灶； 6. 预期生存时间>=3月； 7. 足够器官功能，受试者需满足如下实验室指标： 1) 近14天未使用粒细胞集落刺激因子的情况下，中性粒细胞绝对值（ANC）>=1.5x10^9/L。 2) 近14天未输血的情况下，血小板>=100×10^9/L。 3) 近14天内无输血或使用促红细胞生成素的情况下，血红蛋白>=9 g/dL (90 g/L) or >=5.6 mmol/L； 4) 总胆红素<=1.5×正常值上限（ULN）；或总胆红素>1.5×ULN但直接胆红素<= ULN 5) 天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）在<=2.5×ULN，或发生肝转移的受试者<=5×ULN； 6) 血肌酐<=1.5×ULN并且肌酐清除率（采用Cockcroft-Gault 公式计算）>=60 ml/min； 7) 凝血功能良好： ? 国际标准化比值（INR）或凝血酶原时间（PT）<=1.5倍ULN；或者受试者正在接受抗凝治疗，但凝血酶原时间（PT）或部分凝血活酶时间（PTT）在抗凝剂预期用途的治疗范围内； ? 活化部分凝血活酶时间（aPTT）或部分凝血活酶时间（PTT）<=1.5倍ULN；或者受试者正在接受抗凝治疗，但凝血酶原时间（PT）或活化部分凝血活酶时间（PTT）在抗凝剂预期用途的治疗范围内； 8) 甲状腺功能正常，定义为促甲状腺激素（TSH）在正常范围内。如基线TSH超出正常范围，如果总T3（或FT3）及FT4在正常范围内的受试者亦可入组； 9) 心肌酶谱在正常范围内（如研究者综合判断为不具有临床意义的单纯实验室异常也允许入组）； 8. 对于育龄期女性受试者，应在接受首次研究药物给药（第1周期第1天）之前的3天内接受尿液或血清妊娠试验且结果为阴性。如果尿液妊娠试验结果无法确认为阴性，则要求进行血液妊娠试验。非育龄期女性定义为绝经后至少１年，或进行过手术绝育或子宫切除术； 9. 如存在受孕风险，所有受试者（不论男性或女性）均需在整个治疗期间直至治疗末次研究药物给药后120天（或末次化疗药物给药后180天）内采用年失败率低于1%的避孕措施。

Inclusion criteria

1. Sign written informed consent before implementing any experimental procedures; 2. Gender is not limited, age range is 18-70 years old; 3. As determined by histology or cytology, the researcher assessed it as stage III-IVA (excluding T3-4N0 and T3N1) locally advanced nasopharyngeal carcinoma without any treatment; 4. ECOG PS score is 0-1; According to the criteria for evaluating the efficacy of solid tumors (RECIST version 1.1), there should be at least one measurable lesion on imaging; 6. Expected survival time >= 3 months; 7. Adequate organ function, subjects must meet the following laboratory indicators: 1) In the past 14 days without using granulocyte colony-stimulating factor, the absolute neutrophil count (ANC) was >= 1.5x10^9/L. 2) Platelets >= 100 × 10^9/L without blood transfusion in the past 14 days. 3) Hemoglobin >=9 g/dL (90 g/L) or >= 5.6 mmol/L in the past 14 days without blood transfusion or use of erythropoietin; 4) Total bilirubin <= 1.5 x upper limit of normal (ULN); Or total bilirubin>1.5 × ULN but direct bilirubin <= ULN 5) Aspartate transaminase (AST) and alanine transaminase (ALT) levels are <= 2.5 × ULN, or <= 5 × ULN in subjects with liver metastasis; 6) Blood creatinine <= 1.5 × ULN and creatinine clearance rate (calculated using Cockcroft Gault formula) >= 60 ml/min; 7) Good coagulation function: International normalized ratio (INR) or prothrombin time (PT) <=1.5 times ULN; Or the subject is receiving anticoagulant therapy, but the prothrombin time (PT) or partial thromboplastin time (PTT) is within the therapeutic range of the intended use of the anticoagulant; Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) <= 1.5 times ULN; Or the subject is receiving anticoagulant therapy, but the prothrombin time (PT) or activated partial thromboplastin time (PTT) is within the therapeutic range of the intended use of the anticoagulant; 8) Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; 9) The myocardial enzyme spectrum is within the normal range (simple laboratory abnormalities that are deemed clinically insignificant by the researchers are also allowed to be included); 8. For female subjects of childbearing age, a urine or serum pregnancy test with negative results should be conducted within 3 days prior to the first administration of the study drug (Day 1 of the first cycle). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Non childbearing women are defined as those who have been postmenopausal for at least one year or have undergone surgical sterilization or hysterectomy; 9. If there is a risk of conception, all subjects (male or female) must use contraceptive measures with an annual failure rate of less than 1% throughout the entire treatment period until 120 days after the last administration of the study drug (or 180 days after the last administration of chemotherapy drug).

排除标准：

1. 首次给药前5年内诊断为局晚期鼻咽癌以外的其他恶性肿瘤且未治愈的患者（不包括经过根治的皮肤基底细胞癌、皮肤鳞状上皮癌、和/或经过根治性切除的原位癌）； 2. 当前正在参与干预性临床研究治疗，或在首次给药前4周内接受过其他研究药物或使用过研究器械治疗； 3. 既往接受过下列疗法：抗PD-1、抗PD-L1或抗PD-L2药物或者针对另一种刺激或协同抑制T细胞受体（例如，CTLA-4、OX-40、CD137）的药物； 4. 既往有放疗或化疗史 5. 首次给药前2周内接受过具有抗肿瘤适应症的中成药或免疫调节作用的药物（包括胸腺肽、干扰素、白介素）系统性全身治疗； 6. 首次给药前2年内发生过需要全身性治疗（例如使用缓解疾病药物、糖皮质激素或免疫抑制剂）的活动性自身性免疫疾病。替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性糖皮质激素等）不视为全身性治疗； 7. 研究首次给药前7天内正在接受全身性糖皮质激素治疗（不包括喷鼻、吸入性或其他途径的局部糖皮质激素）或任何其他形式的免疫抑制疗法； 注：允许使用生理剂量的糖皮质激素（<=10 mg/天的泼尼松或等效药物）； 8. 已知异体器官移植（角膜移植除外）或异体造血干细胞移植； 9. 已知对本研究药物信迪利单抗活性成分或辅料，及本研究化疗药物过敏者; 10. 在开始治疗前，尚未从任何干预措施引起的毒性和/或并发症中充分恢复（即，≤1级或达到基线，不包括乏力或脱发）； 11. 已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）； 12. 未经治疗的活动性乙肝（定义为HBsAg阳性同时检测到HBV-DNA拷贝数大于所在研究中心检验科正常值上限）； 注：符合下列标准的乙肝受试者亦可入组： 1) 首次给药前HBV病毒载量<1000拷贝/ml（200 IU/ml），受试者应在整个研究药物治疗期间接受抗HBV治疗避免病毒再激活 2) 对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活 13. 活动性的HCV感染受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）； 14. 首次给药之前（第 1 周期，第 1 天）30 天内接种过活疫苗； 注：允许首次给药前 30 天内接受针对季节性流感的注射用灭活病毒疫苗；但是不允许接受鼻内用药的减毒活流感疫苗。 15. 妊娠或哺乳期妇女； 16. 存在任何严重或不能控制的全身性疾病，例如： 1) 静息心电图在节律、传导或形态上出现有重大且症状严重难以控制的异常，如完全性左束支传导阻滞，Ⅱ度以上心脏传导阻滞，室性心律失常或心房颤动； 2) 不稳定型心绞痛，充血性心力衰竭，纽约心脏病协会（NYHA）分级>=2 级的慢性心衰； 3) 在入选治疗前6个月内发生过任何动脉血栓、栓塞或缺血，如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作等； 4) 血压控制不理想（收缩压＞140 mmHg，舒张压＞90 mmHg）； 5) 首次给药前1年内存在需要糖皮质激素治疗的非感染性肺炎病史，或当前存在临床活动性间质性肺病； 6) 活动性肺结核； 7) 存在需要全身性治疗的活动性或未能控制的感染； 8) 存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻； 9) 肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎； 10) 糖尿病控制不佳（空腹血糖（FBG）＞10mmol/L）； 11) 尿常规提示尿蛋白>=++，且证实24小时尿蛋白定量＞1.0 g者； 12) 存在精神障碍且无法配合治疗的患者； 17. 有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况，研究者认为存在其他潜在风险不适合参加本研究。

Exclusion criteria：

1. Patients diagnosed with other malignant tumors other than locally advanced nasopharyngeal carcinoma within 5 years before the first administration and who have not been cured (excluding skin basal cell carcinoma, skin squamous cell carcinoma, and/or carcinoma in situ that has undergone radical resection); 2. Currently participating in interventional clinical research treatment, or having received other research drugs or used research instruments for treatment within 4 weeks before the first administration; 3. Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs that stimulate or synergistically inhibit T cell receptors (such as CTLA-4, OX-40, CD137); 4. History of radiation therapy or chemotherapy in the past 5. Have received systematic systemic treatment with traditional Chinese patent medicines and simple preparations with anti-tumor indications or drugs with immunomodulatory effect (including thymosin, interferon and interleukin) within 2 weeks before the first administration; Within 2 years prior to the first administration, there has been an active autoimmune disease requiring systemic treatment (such as the use of disease relieving drugs, corticosteroids, or immunosuppressants). Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered systemic treatments; 7. Within 7 days prior to the first administration of the study, the individual was receiving systemic corticosteroid therapy (excluding topical corticosteroids via nasal spray, inhalation, or other routes) or any other form of immunosuppressive therapy; Note: Physiological doses of glucocorticoids (<= 10 mg/day of prednisone or equivalent) are allowed to be used; 8. Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 9. Individuals who are known to be allergic to the active ingredients or excipients of the investigational drug Xindilimumab, as well as the chemotherapy drugs used in this study; 10. Prior to commencing treatment, the individual has not fully recovered from any toxicity and/or complications caused by any intervention measures (i.e., ≤ grade 1 or baseline, excluding fatigue or hair loss); 11. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 12. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected is greater than the upper limit of normal value in the laboratory of the research center); Note: hepatitis B patients who meet the following criteria can also be included in the group: 1) Before the first administration, the HBV viral load was less than 1000 copies/ml (200 IU/ml), and subjects should receive anti HBV treatment throughout the entire study drug treatment period to avoid viral reactivation 2) For subjects with anti HBc (+), HBsAg (-), anti HBs (-), and HBV viral load (-), prophylactic anti HBV treatment is not necessary, but close monitoring of viral reactivation is necessary 13. Active HCV infected subjects (HCV antibody positive and HCV-RNA level above the detection limit); 14. Administer a live vaccine within 30 days prior to the first dose (Day 1 of the first cycle); Note: It is allowed to receive inactivated vaccine for seasonal influenza within 30 days before the first administration; However, intranasal administration of attenuated live influenza vaccine is not allowed. 15. Pregnant or lactating women; 16. There are any serious or uncontrollable systemic diseases, such as: 1) Resting electrocardiogram shows significant and difficult to control abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, grade II or higher heart block, ventricular arrhythmia, or atrial fibrillation; 2) Unstable angina pectoris, congestive heart failure, chronic heart failure classified as NYHA >= 2; 3) Any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, occurred within the 6 months prior to being selected for treatment; 4) Poor blood pressure control (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg); 5) A history of non infectious pneumonia requiring corticosteroid treatment within the year prior to the first administration, or current clinical active interstitial lung disease; 6) Active pulmonary tuberculosis; 7) There are active or uncontrolled infections that require systemic treatment; 8) There is clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction; 9) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; 10) Poor control of diabetes (FBG>10mmol/L); 11) Urine routine shows urinary protein >=++and confirms 24-hour urinary protein quantification>1.0 g; 12) Patients with mental disorders who are unable to cooperate with treatment; 17. Medical history or disease evidence, abnormal treatment or laboratory test values that may interfere with the trial results, hinder the full participation of the subjects in the study, or other situations that the researchers believe are not suitable for inclusion. The researchers believe that there are other potential risks and they are not suitable to participate in this study.

研究实施时间：

Study execute time：

从 From 2025-09-21 00:00:00至 To 2029-10-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-10-01 00:00:00 至 To 2027-10-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

40

Group：

Experimental group

Sample size：

干预措施：

信迪利单抗（200mg，Q3W）+吉西他滨（1000mg/m2，D1、8，Q3W）+顺铂（80mg/m2，D1）3周期 IMPT（6996cGy/33F）+吉西他滨（1000mg/m2，D1、8，Q3W）+顺铂（40mg/m2，D1,8,15），2周期

干预措施代码：

Intervention：

sintilimab(200mg,Q3W)+gemcitabine(1000mg/m2,D18,Q3W)+cisplatin(80mg/m2,D1),3 cycles IMPT(6996cGy/33F)+gemcitabine(1000mg/m2,D18,Q3W)+cisplatin(40mg/m2,D1,8,15),2 cycles

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 安徽 

市(区县)：

  

Country：

China 

Province：

Anhui 

City：

 

单位(医院)：

安徽省肿瘤医院 

单位级别：

三甲 

Institution
hospital：

Anhui Provincial Cancer Hospital

Level of the institution：

Tertiary A

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, 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：

3年生存率

指标类型：

次要指标

Outcome：

3y-overall survival rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

3年无病生存率

指标类型：

次要指标

Outcome：

3y-disease-free-survival rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性和耐受性

指标类型：

次要指标

Outcome：

Safety and tolerability

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：

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：

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：

无

Blinding：

None

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

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：

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：

暂未确定/Not yet

注册人：

Name of Registration：

  2025-09-25 11:33:15