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：	ChiCTR2200066119
最近更新日期： Date of Last Refreshed on：	2024-07-31 18:40:49
注册时间： Date of Registration：	2022-11-24 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	卡瑞利珠单抗联合白蛋白紫杉醇/顺铂术前新辅助治疗局部晚期口腔鳞癌的II期临床研究
Public title：	Neoadjuvant camrelizumab plus albumin paclitaxel and cisplatin in locally advanced oral squamous cell carcinoma: A phase II Clinical Trial
注册题目简写：
English Acronym：
研究课题的正式科学名称：	卡瑞利珠单抗联合白蛋白紫杉醇/顺铂术前新辅助治疗局部晚期口腔鳞癌的II期临床研究
Scientific title：	Camrelizumab plus albumin paclitaxel and cisplatin in locally advanced oral squamous cell carcinoma: A phase II 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：	向中正	研究负责人：	刘磊
Applicant：	Zhongzheng Xiang	Study leader：	Lei Liu
申请注册联系人电话： Applicant telephone：	+86 185 8390 7360	研究负责人电话： Study leader's telephone：	+86 189 8060 6231
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：	1530549632@qq.com	研究负责人电子邮件： Study leader's E-mail：	liuleihx@gmail.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：	四川省成都市武侯区国学巷37号	研究负责人通讯地址：	四川省成都市武侯区国学巷37号
Applicant address：	37 Guo Xue Alley, Chengdu, Sichuan, China	Study leader's address：	37 Guo Xue Alley, Chengdu, Sichuan, 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：	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：	2022年审(899)号; 2022年审(899)号(2024年修正案)	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：	Ethics Committee on Biomedical Research, West China Hospital of Sichuan University
伦理委员会批准日期： Date of approved by ethic committee：	2022-11-10 00:00:00
伦理委员会联系人：	邓绍林
Contact Name of the ethic committee：	Shaolin Deng
伦理委员会联系地址：	四川省成都市武侯区国学巷37号
Contact Address of the ethic committee：	37 Guo Xue Alley, Chengdu, Sichuan, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 28 8542 2654	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：

四川省成都市武侯区国学巷37号

Primary sponsor's address：

37 Guo Xue Alley, 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)：	四川省	市(区县)：	成都市
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：	37 Guo Xue Alley, Chengdu, Sichuan, China

经费或物资来源：

四川大学华西医院临床研究孵化项目（50.0万人民币）；恒瑞公司免费赠送卡瑞利珠单抗和白蛋白紫杉醇药物

Source(s) of funding：

Clinical Research Incubation Project of West China Hospital of Sichuan University (RMB 500,000); Jiangsu Hengrui Pharmaceuticals Co.,Ltd. gives free of charge for camrelizumab and albumin paclitaxel.

研究疾病：

局部晚期口腔鳞癌

Target disease：

Locally advanced oral 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：

1.主要研究目标 1）评估卡瑞利珠单抗联合白蛋白紫杉醇/顺铂术前新辅助治疗局部晚期口腔鳞癌的有效性和安全性 2）观察患者无疾病进展生存期（Disease-free survival, DFS） 3）观察患者总体生存期（Overall survival, OS） 2.次要研究目标 1）评估术前新辅助治疗后病理缓解率与患者长期生存之间的相关性 2）评估患者PD-L1表达水平与患者生存之间的相关性

Objectives of Study：

1. Main research objectives (1) Evaluation of the efficacy and safety of preoperative neoadjuvant therapy with Carilizumab combined with albumin paclitaxel/cisplatin for locally advanced oral squamous cell carcinoma; (2) Observe the disease-free survival (DFS) of patients without disease progression; (3) Observe the overall survival (OS) of patients; 2. Secondary research objectives (1) Evaluate the correlation between pathological remission rate after preoperative neoadjuvant therapy and long-term survival of patients; (2) Assessing the correlation between PD-L1 expression levels and patient survival.

药物成份或治疗方案详述：

治疗方案 1.术前新辅助治疗符合纳入排除标准的受试者首先接受2周期卡瑞利珠单抗（200 mg，D1，ivgtt）+白蛋白紫杉醇（260 mg/m2, D1，ivgtt）+顺铂（75 mg/m2, 分成3天给药，ivgtt）方案治疗，每3周一次（注：新辅助治疗前由华西口腔医院外科医生使用染料对原发病灶进行标记，至少包括最短径和最长径在内的4个标记点，以观察病灶对新辅助治疗的反应，同时为后续手术切除范围提供参考）。 2.手术治疗新辅助治疗结束后间隔2-4周进行手术，根据肿瘤组织的侵犯范围选择行根治性切除原发病灶或颈部淋巴结清扫术，适当采用带蒂或游离皮瓣对术后缺损进行修复。 3.术后辅助治疗综合评估患者年龄、伴随疾病状况、术后病理分期、手术切缘情况、淋巴结累及范围以及原发肿瘤的其他组织病理学特征之后决定是否进行术后辅助放疗或辅助放化疗（具体依据以下危险因素：对于术后有高危因素，如III-IV期、近切缘、肿瘤浸润深度＞ 10mm、脉管癌栓、神经侵犯、淋巴结阳性等的患者行单纯放疗，对于术后手术切缘阳性或淋巴结包膜外侵的患者行顺铂为基础的同步放化疗）。同时，术后给予患者6周期卡瑞利珠单抗（200mg, ivgtt, q3w）辅助维持治疗。在根治手术后4-6周内进行放疗，采用IMRT调强放疗技术，1.8-2 Gy/次，1次/天，5次/周，54-66 Gy，期间部分患者同步顺铂（100mg/m2），每3周一次，共3周期。

Description for medicine or protocol of treatment in detail：

Treatment plan 1. Neoadjuvant treatment before surgery Subjects who met the inclusion and exclusion criteria firstly receive a 2-cycle regimen of camrelizumab plus (200 mg, D1, ivgtt)+albumin paclitaxel (260 mg/m^2, D1, ivgtt)+cisplatin (75 mg/m^2, divided into 3 days, ivgtt), once every 3 weeks (Note: before the new adjuvant treatment, the surgeon of West China Stomatological Hospital will use dye to mark the primary lesion, including at least 4 marker points including the shortest and longest diameter, to observe the reaction of the lesion to the neoadjuvant treatment and provide reference for the scope of subsequent surgical resection); 2. Surgical treatment After the completion of the neoadjuvant treatment, the surgery should be performed at an interval of 2-3 weeks. According to the extent of invasion of the tumor tissue, radical resection of the primary lesion or neck lymph node dissection should be performed, and pedicled or free flaps should be properly used to repair the postoperative defects; 3. Adjuvant treatment after operation Comprehensively evaluate the patient's age, accompanying diseases, postoperative pathological staging, surgical margin, the range of lymph node involvement and other histopathological characteristics of the primary tumor, to decide whether to carry out postoperative adjuvant radiotherapy or adjuvant radiotherapy and chemotherapy (the specific risk factors are as follows: patients with high risk factors after surgery, such as stage III-IV, positive margin, tumor invasion depth>10mm, vascular cancer thrombus, nerve invasion, lymph node positive, etc., should be treated with radiotherapy alone, and patients with positive surgical margin or lymph node capsule invasion after surgery should be treated with cisplatin based concurrent radiotherapy). At the same time, patients were given 6 cycles of camrelizumab (200mg, ivgtt, q3w) as an adjuvant maintenance treatment after surgery; Radiotherapy was carried out within 4-6 weeks after radical surgery, using IMRT (intensity modulated radiotherapy technology), 1.8-2 Gy/F, 1 F/day, 5 times/week, 54-66 Gy. During this period, some patients were concurrently with cisplatin (100mg/m2, ivgtt), once every 3 weeks, a total of 3 cycles.

纳入标准：

Inclusion criteria

1. Age: 18-75 years old;
2. Histopathological diagnosis of oral squamous cell carcinoma (including tongue cancer, gingival cancer, buccal mucosal cancer, oral floor cancer, and posterior triangular area tumor of molars);
3. Patients with locally advanced oral squamous cell carcinoma (classified as stage III-IVB according to the 8th edition of UICC/AJCC staging);
4. ECOG score 0-1 points;
5. Have not received any relevant treatment in the past;
6. No distant metastasis;
7. The patient intends for curative treatment;
8. Good hematopoietic function (total white blood cell count >= 3.5 × 10^9/L, absolute lymphocyte count >= 0.8 × 10^9/L, absolute neutrophil count >= 1.5 × 10^9/L, platelet count >= 100 × 10^9/L, hemoglobin ≥ 90g/L);
9. Good liver function (bilirubin level <= 1.5 times the upper limit of normal (ULN)); AST and ALT levels <= 2.5 times ULN;
10. Good renal function (serum creatinine <= 1.5 times ULN or calculated creatinine clearance rate >= 60 ml/min (Cockcroft Gault formula), urine protein content less than 2+on urine routine examination, or 24-hour urine protein quantification<1g);
11. Good coagulation function, defined as an international normalized ratio (INR) or prothrombin time (PT) <= 1.5 times ULN. If the subject is receiving anticoagulant therapy, as long as the PT is within the intended range of use of the anticoagulant drug, it is sufficient;
12. No severe organic heart disease or arrhythmia;
13. Women of childbearing age (15-49 years old) must undergo pregnancy studies within 7 days before starting treatment and the results must be negative; Male and female patients with fertility must agree to use effective contraceptive measures to ensure that they do not become pregnant during the study period and within 3 months after discontinuing treatment.

排除标准：

1. 有远处转移病灶； 2. 拒绝手术治疗患者； 3. 姑息性治疗意图患者； 4. 既往接受过针对原发灶或转移淋巴结任何形式的抗肿瘤治疗，包括化疗、放疗、靶向治疗、抗PD-1或PD-L1治疗或手术等（除外活检）； 5. 有其他恶性肿瘤疾病； 6. 活动性感染； 7. 既往接受过器官移植； 8. 有自身免疫疾病历史，或者其他疾病需要长期全身性使用激素类药物或者免疫抑制治疗； 9. 人类免疫缺陷病毒（HIV）阳性； 10. 活动性乙型或丙型肝炎感染（HBV DNA、HCV RNA超过正常值上限）； 11. 白细胞总数<3.5×10^9/L，淋巴细胞数绝对值<0.8×10^9/L，中性粒细胞<1.5×10^9/L、血小板<100×10^9/L、血红蛋白<90g/L；胆红素>1.5倍正常值上限，转氨酶（AST、ALT）>3倍正常值上限（如果肝转移为5倍正常值上限），血清肌酐>1.5倍正常值上限；凝血功能异常，国际标准化比值（INR）或凝血酶原时间（PT）>1.5倍正常值上限； 12. 严重的心血管、呼吸系统，或免疫系统重大并发疾病；包括泌尿道阻塞，心肌梗塞，心律失常，阻塞性或限制性肺病，或其他研究者认为可能会增加受试者风险的疾病； 13. 妊娠或哺乳期女性； 14. 患者不同意在治疗期间及随后的3个月内使用有效避孕措施； 15. 同时参加其他临床研究的患者； 16. 病情危重不能完成调查的患者； 17. 既往有精神病史者（如：精神分裂症、躁狂症、焦虑症、抑郁症、恐怖症等）或者临床试验入组时被确诊精神疾病的患者或配偶； 18. 意识模糊、失语、智障等原因导致沟通交流障碍、无法正常作答的患者或配偶； 19. 过敏体质和先天免疫缺陷患者； 20. 不能耐受免疫治疗的患者； 21.研究者认为存在不适合入选或影响受试者参与或完成研究的其他因素。

Exclusion criteria：

1. There are distant metastatic lesions; 2. Refusing surgical treatment for patients; 3. Patients with palliative care intentions; 4. Previously received any form of anti-tumor treatment targeting the primary lesion or metastatic lymph nodes, including chemotherapy, radiotherapy, targeted therapy, anti-PD-1 or PD-L1 therapy, or surgery (excluding biopsy); 5. There are other malignant tumor diseases; 6. Active infection; 7. Previously received organ transplantation; 8. Having a history of autoimmune diseases or requiring long-term systemic use of steroid drugs or immunosuppressive therapy for other illnesses; 9. Positive for Human Immunodeficiency Virus (HIV); 10. Active hepatitis B or C infection (HBV DNA, HCV RNA exceeding the upper limit of normal values); 11. Total white blood cell count<3.5 × 10^9/L, absolute lymphocyte count<0.8 × 10^9/L, neutrophils<1.5 × 10^9/L, platelets<100 × 10^9/L, hemoglobin<90g/L; Bilirubin>1.5 times the upper limit of normal value, transaminase (AST, ALT)>3 times the upper limit of normal value (if liver metastasis is 5 times the upper limit of normal value), serum creatinine>1.5 times the upper limit of normal value; Abnormal coagulation function, international normalized ratio (INR) or prothrombin time (PT)>1.5 times the upper limit of normal value; 12. Serious cardiovascular, respiratory, or immune system complications; Including urinary tract obstruction, myocardial infarction, arrhythmia, obstructive or restrictive lung disease, or other diseases that researchers believe may increase the risk of the subjects; 13. Pregnant or lactating women; 14. The patient does not agree to use effective contraceptive measures during the treatment period and the following 3 months; 15. Patients who participate in other clinical studies simultaneously; 16. Patients who are critically ill and unable to complete the investigation; 17. Individuals with a history of mental illness (such as schizophrenia, mania, anxiety, depression, phobias, etc.) or patients or spouses diagnosed with mental illness at the time of clinical trial enrollment; 18. Patients or spouses who have communication barriers or are unable to answer questions normally due to reasons such as blurred consciousness, aphasia, intellectual disability, etc; 19. Allergic constitution and congenital immunodeficiency patients; 20. Patients who cannot tolerate immunotherapy; 21. The researcher believes that there are other factors that are not suitable for inclusion or affect the participation or completion of the study by the subjects.

研究实施时间：

Study execute time：

从 From 2022-12-01 00:00:00至 To 2025-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-01-30 00:00:00 至 To 2025-12-25 00:00:00

干预措施：

Interventions：

组别：	单臂治疗组	样本量：	31
Group：	Single arm treatment group	Sample size：	31
干预措施：	首先接受2周期卡瑞利珠单抗（200 mg，D1，ivgtt）+白蛋白紫杉醇（260 mg/m2, D1，ivgtt）+顺铂（75 mg/m2, 分成3天给药，ivgtt）方案治疗，每3周一次；然后进行根治性手术；最后进行术后辅助放（化）疗联合卡瑞利珠单抗维持治疗6周期	干预措施代码：	1
Intervention：	First of all, patients were treated with 2-cycle regimen of camrelizumab plus (200 mg, D1, ivgtt)+albumin paclitaxel (260 mg/m^2, D1, ivgtt)+cisplatin (75 mg/m^2, divided into 3days, ivgtt), once every 3 weeks; Then carry out radical operation; Finally, postoperative adjuvant radiotherapy (chemotherapy) combined with maintenance therapy	Intervention code：	1

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	四川省	市(区县)：	成都市
Country：	China	Province：	Sichuan	City：	Chengdu
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：	主要病理缓解率	指标类型：	主要指标
Outcome：	Major pathological response (MPR)	Type：	Primary indicator
测量时间点：	手术治疗后	测量方法：	术后肿瘤组织H&E切片上残余可见肿瘤与总体肿瘤瘤床面积的比值百分数 ≤ 10%患者比例
Measure time point of outcome：	After surgery	Measure method：	The proportion of patients with residual visible tumors on H&E sections of postoperative tumor tissue and a ratio of tumor bed area to the overall tumor bed area of <= 10%

指标中文名：	安全性	指标类型：	主要指标
Outcome：	Safety	Type：	Primary indicator
测量时间点：	整体治疗期间	测量方法：	治疗期间观察随访患者症状体征
Measure time point of outcome：	During the entire treatment period	Measure method：	Observation and follow-up of patients' symptoms and signs during treatment

指标中文名：	客观反应率	指标类型：	次要指标
Outcome：	Objective response rate (ORR)	Type：	Secondary indicator
测量时间点：	新辅助治疗后，手术前	测量方法：	计算新辅助治疗前后核磁共振图像中肿瘤最大径缩小至少30%的患者占比
Measure time point of outcome：	After neoadjuvant therapy, before surgery	Measure method：	Calculate the proportion of patients with tumor maximum diameter reduction of at least 30% in MRI images before and after neoadjuvant therapy

指标中文名：	无疾病生存期	指标类型：	次要指标
Outcome：	Disease-free survival (DFS)	Type：	Secondary indicator
测量时间点：	治疗结束后2年内每3月1次，2-5年内每6月1次，5年后每年1次	测量方法：	定期行核磁共振、CT等影像学检查
Measure time point of outcome：	Within 2 years after treatment, once every 3 months; within 2-5 years, once every 6 months; and after 5 years, once a year	Measure method：	Regular MRI, CT and other imaging examinations

指标中文名：	总体生存期	指标类型：	次要指标
Outcome：	Overall survival (OS)	Type：	Secondary indicator
测量时间点：	治疗结束后2年内每3月1次，2-5年内每6月1次，5年后每年1次	测量方法：	电话随访
Measure time point of outcome：	Within 2 years after treatment, once every 3 months; within 2-5 years, once every 6 months; and after 5 years, once a year	Measure method：	Telephone follow-up

指标中文名：	病理缓解与生存期的相关性	指标类型：	次要指标
Outcome：	The correlation between pathological remission and survival period	Type：	Secondary indicator
测量时间点：	治疗结束1-2年后	测量方法：	斯皮尔曼相关系数分析
Measure time point of outcome：	1-2 years after the end of treatment	Measure method：	Spearman's correlation analysis

指标中文名：	病理完全缓解率	指标类型：	次要指标
Outcome：	Pathological complete response (pCR)	Type：	Secondary indicator
测量时间点：	手术后	测量方法：	术后肿瘤组织H&E切片上无肿瘤细胞残留患者的占比
Measure time point of outcome：	After surgery	Measure method：	The proportion of patients with no residual tumor cells on H&E sections of postoperative tumor tissue

指标中文名：	生物-影像标志物分析	指标类型：	附加指标
Outcome：	bio-radiomic markers analysis	Type：	Additional indicator
测量时间点：	新辅助治疗前后	测量方法：	新辅助治疗前后收集患者肿瘤组织进行生物标记物检测分析；新辅助治疗前后进行MRI（OGSE）扫描进行影像组学标志物分析
Measure time point of outcome：	Before and after neoadjuvant immunochemotherapy	Measure method：	Collecting tumor tissues from patients before and after neoadjuvant therapy for biomarker detection and analysis; performing MRI (OGSE) scans for radiomics biomarker analysis before and after neoadjuvant therapy

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：	血液
Sample Name：	Blood	Tissue：	Blood
人体标本去向	使用后销毁	说明	使用后销毁
Fate of sample：	Destruction after use	Note：	Destruction after use

标本中文名：	肿瘤组织	组织：	肿瘤组织
Sample Name：	Tumor tissue	Tissue：	Tumor tissue
人体标本去向	使用后销毁	说明	使用后保存
Fate of sample：	Destruction after use	Note：	Preservation after use

征募研究对象情况：

Recruiting status：

结束

/Completed

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）：

单臂II期临床研究，无需随机

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

Single arm Phase II clinical study without randomization.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：	单臂II期临床研究，无需设盲
Blinding：	Single arm Phase II clinical study, without blinding.

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）：	ResMan, http://www.medresman.org.cn/login.aspx
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	ResMan, http://www.medresman.org.cn/login.aspx
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：	本研究将采用EDC系统，研究数据将由研究者或授权的研究人员录入到电子病例报告表（eCRF）中。研究中心启动或数据录入前，将对研究者和授权的研究人员进行适当培训，并对所使用的电脑等设备采取适当的安全措施。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	This study uses an electronic data collection (EDC) System, and research data will be entered into an electronic case report form (eCRF) by researchers or authorized personnel. Prior to the launch of the research center or data entry, appropriate training will be provided to researchers and authorized personnel, and appropriate security measures will be taken for the computers and other equipment used.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2022-11-24 17:47:48