ChiCTR2300075094 版本V1.0 版本创建时间2023/08/24 16:46:04 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：

ChiCTR2300075094 

最近更新日期：

Date of Last Refreshed on：

2023-08-24 16:45:36 

注册时间：

Date of Registration：

2023-08-24 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

PD-1单抗和尼妥珠单抗联合GP方案诱导化疗和同期放化疗加卡培他滨辅助治疗 T3-4N3M0 鼻咽癌：一项单臂、前瞻性的II期临床研究

Public title：

PD-1 inhibitor and nimotuzumab plus induction chemotherapy, concurrent therapy, in combination with capecitabine as adjuvant therapy, for T3-4N3M0 nasopharyngeal carcinoma: a single arm, phase II clinical trial

注册题目简写：

English Acronym：

研究课题的正式科学名称：

PD-1单抗和尼妥珠单抗联合GP方案诱导化疗和同期放化疗加卡培他滨辅助治疗 T3-4N3M0 鼻咽癌：一项单臂、前瞻性的II期临床研究

Scientific title：

PD-1 inhibitor and nimotuzumab plus induction chemotherapy, concurrent therapy, in combination with capecitabine as adjuvant therapy, for T3-4N3M0 nasopharyngeal carcinoma: a single arm, 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：

钟桂华 

研究负责人：

刘志刚 

Applicant：

Guihua Zhong 

Study leader：

Zhigang Liu 

申请注册联系人电话：

Applicant telephone：

+86 769 2863 7916

研究负责人电话：

Study leader's telephone：

+86 769 2863 7916

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：

237446361@qq.com

研究负责人电子邮件：

Study leader's E-mail：

85172626@qq.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：

广东省东莞市万江街道万道路新谷涌78号

研究负责人通讯地址：

广东省东莞市万江街道万道路新谷涌78号

Applicant address：

78, Wandao Street, Wanjiang Road, Dongguan, Guangdong Province, China

Study leader's address：

78, Wandao Street, Wanjiang Road, Dongguan, Guangdong Province, 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：

南方医科大学第十附属医院(东莞市人民医院)

Applicant's institution：

The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital)

研究负责人所在单位：

南方医科大学第十附属医院(东莞市人民医院)

Affiliation of the Leader：

The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's 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：

KYKT2023-010

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：

东莞市人民医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Dongguan People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2023-08-22 00:00:00

伦理委员会联系人：

袁领勤

Contact Name of the ethic committee：

Lingqin Yuan

伦理委员会联系地址：

广东省东莞市万江街道万道路78号

Contact Address of the ethic committee：

78, Wandao Street, Wanjiang Road, Dongguan, Guangdong Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 769 2863 6365

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：

南方医科大学第十附属医院(东莞市人民医院)

Primary sponsor：

The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital)

研究实施负责（组长）单位地址：

广东省东莞市万江街道万道路78号

Primary sponsor's address：

78, Wandao Street, Wanjiang Road, Dongguan, Guangdong Province, 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)：

东莞

Country：

China

Province：

Guangdong

City：

Dongguan

单位(医院)：

南方医科大学第十附属医院(东莞市人民医院)

具体地址：

广东省东莞市万江街道万道路78号

Institution
hospital：

The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital)

Address：

78, Wandao Street, Wanjiang Road, Dongguan, Guangdong Province, China

经费或物资来源：

百泰生物药业有限公司

Source(s) of funding：

Biotech Pharmaceutical Co., Ltd

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：

 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单抗和尼妥珠单抗联合GP方案诱导化疗和同期放化疗加卡培他滨辅助治疗T3-4N3M0鼻咽癌的无进展生存 (Progression-free survival, PFS)、 总生存 (Overall survival, OS)、无局部区域复发进展生存 (Locoregional failure-free survival, LRFFS)、无远处转移生存 (Distant metastasis-free survival, DMFS)、诱导治疗后客观缓解率（objective response rate, ORR)及安全性。 2、基于肿瘤组织和血液检测，探索在T3-4N3M0鼻咽癌患者综合治疗疗效评估的生物标志物。  

Objectives of Study：

1. Primary objectives: To evaluate the efficacy (including progression-free survival, overall survival, objective response rate and disease control rate) and safety of PD-1 inhibitor and nimotuzumab plus induction chemotherapy, concurrent therapy, in combination with capecitabine as adjuvant therapy, for T3-4N3M0 nasopharyngeal carcinoma 2. Secondary objective: based on tumor tissue and blood to explore the potential biomarkers of comprehensive therapy for T3-4N3M0 nasopharyngeal carcinoma and their prognostic values.

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）病理学或细胞学确诊的鼻咽癌； （2）初诊患者影像学评估分期为T3-4N3M0鼻咽癌（所有入组患者均由≥2 名中级职称以上的放射治疗科医师或医学影像科医师根据 AJCC/UICC 第 8版鼻咽癌 TNM 分期标准进行分期）； （3）初诊患者未经任何抗肿瘤治疗，包括放疗、化疗、靶向治疗和免疫治疗等； （4）年龄为18-65岁之间； （5）ECOG体能状态评分（PS评分）0或1； （6）主要器官功能符合下列标准（14天内不允许使用任何血液成分及细胞生长因子）： a. 中性粒细胞计数≥1.5×10 9/L，血红蛋白≥ 90g/L 以及血小板计数≥100×109/L； b. 谷丙转氨酶(ALT)/谷草转氨酶 (AST)≤1.5 倍的正常值上限 (upper limit of normal, ULN)，胆红素≤1.5×ULN，碱性磷酸酶<2.5×ULN； c. 肌酐清除率≥ 50 ml/min（根据 Cockcroft-Gault 公式计算）； d. 活化部分凝血酶时间（APTT）和国际标准化比值（INR）≤1.5×ULN（接受稳定剂量抗凝治疗的受试者，如低分子肝素或华法林，其INR在预期治疗范围内可以筛选）； （7）根据RECIST 1.1 标准，至少有一个可测量病灶； （8）预计生存期 ≥ 12周； （9）有妊娠能力的女性和有生育能力的男性受试者应在研究治疗期间采取医学公认的避孕措施（卡瑞利珠单抗末次给药后至少3个月；末次化疗后至少6个月后）； （10）受试者自愿加入本研究，签署知情同意书，依从性好，配合随访。

Inclusion criteria

(1) Patients pathologically diagnosed with nasopharyngeal carcinoma; (2) Patients newly diagnosed with advanced nasopharyngeal carcinoma at Stage T3-4N3M0 defined by the American Journal of Critical Care (AJCC) staging system (the 8th edition) by two or more experienced radiation oncologists or radiologists; (3) Patients who have not received any anti-tumor treatments, including radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc; (4) Aged ≥ 18 years and ≤ 65 years; (5) The Eastern Cooperative Oncology Group (ECOG) score: 0~1 point; (6) The function of vital organs meet the following requirements (it is not allowed to use any blood component, cell growth factors, white blood cell-increasing drugs, platelet-increasing drugs, and drugs to correct anemia within 14 days prior to the first dose of the study drug) a. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Hemoglobin ≥ 90 g/L; Platelet count ≥ 100 × 10^9/L; b. ALT and/or AST ≤ 2.5 × ULN, ALT and/or AST ≤ 5 × ULN, total bilirubin ≤ 1.5 × ULN, ALP < 2.5 × ULN c. Creatinine clearance ≥50 mL/min (Cockcroft-Gault); d. APTT≤1.5×ULN, INR≤1.5×ULN (Patiants receiving stable doses of anticoagulation therapy, such as low molecular weight heparin or warfarin, and whose INR falls within the expected therapeutic range, may be eligible for screening.) (7) Patients who have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), and the lesion should not have received radiotherapy or other local treatment; (8) Expected survival ≥12 weeks; (9) Female subjects with childbearing potential and male subjects whose partners are women of childbearing age should take one medically recognized contraceptive measure during the study treatment period, at least 3 months after the last dose of camrelizumab, and at least 6 months after the last use of chemotherapy; (10) Subjects who are voluntary to join the study, sign the informed consent form, have good compliance and cooperate with follow-up.

排除标准：

（1）既往对PD-1单抗、尼妥珠单抗、吉西他滨、顺铂和卡培他滨中任何药物或其成分有过敏史； （2） 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； （3）同时参加另一临床研究的受试者，除外观察性研究； （4）未能控制的心脏临床症状或疾病，如：①NYHAⅡ级以上心力衰竭；②不稳定型心绞痛；③1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； （6）首次使用研究药物前4周内发生过严重感染（CTCAE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）；但不包括：使用稳定剂量的甲状腺替代激素治疗的自身免疫介导的甲状腺功能减退症；使用稳定剂量的胰岛素I型糖尿病；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）有间质性肺病病史（不包括不含激素治疗的放射性肺炎）或非感染性肺炎病史； （10）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； （11）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）； （12）会干扰口服药物的疾病，包括吞咽困难、慢性腹泻或肠梗阻； （13）已知有精神类药物的滥用、酗酒及吸毒史； （14）怀孕或哺乳期妇女； （15）经研究者判断可能影响受试者安全或试验依从性的其他情况，包括但不限于不稳定性心脏病、肾病、控制不佳的糖尿病、情绪障碍等。

Exclusion criteria：

(1) Patients with a past history of allergy to any component of PD-1 inhibitor, nimotuzumab, gemcitabine, cisplatin and capecitabine or its components; (2) Patients previously before 5 years or concurrently suffering from other malignant tumors (except for malignant tumors which have been cured with cancer-free survival of more than 5 years, such as cutaneous basal cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, etc.); (3) Patients who participated in another clinical study at the same time, except for the observational study; (4) Patients with uncontrolled cardiac clinical symptoms or diseases, such as: a. NYHA grade II or higher heart failure; b. unstable angina; c. myocardial infarction that has occurred in the past 1 year; d. supraventricular or ventricular arrhythmia with clinical significance and requiring clinical intervention; (5) Patients who have received any of the following treatments: a. Patients who have previously received anti-PD-1, anti-PD-1 antibody or anti-CTLA-4 antibody treatment; b. Patients who are concurrently enrolled into another clinical study, unless the study is observational (non-interventional) clinical study or interventional clinical study follow-up; c. Subjects who need to receive systematic treatment with corticosteroids (>10 mg prednisone equivalent dose/day) or other immunosuppressive agents, except for the use of corticosteroids for local inflammation and prevention of allergies and nausea and vomiting. Other special cases require communication with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal cortical hormone replacement therapy with at a dose >10 mg/day therapeutically effective dose of prednisone are allowed; d. Patients who have received inoculation of tumor vaccines or have received live vaccines within 4 weeks prior to the first dose of the study drug; e. Patients who have undergone major surgery or had a severe trauma within 4 weeks prior to the first dose of the study drug; (6) Patients who have developed severe infection (CTC AE > grade 2) within 4 weeks prior to the first dose of the study drug, such as severe pneumonia, bacteremia and complication of infection that require hospitalization; patients whose baseline chest imaging findings suggest active pulmonary inflammation, or patients with symptoms and signs of infection within 2 weeks prior to the first dose of the study drug or need to be treated with oral or intravenous antibiotics (excluding prophylactic use of antibiotics); (7) Patients with active autoimmune diseases or a history of autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism and hypothyroidism, including but not limited to these diseases or syndromes); but excluding autoimmune-mediated hypothyroidism using a stable dose of thyroid replacement hormone therapy; type I diabetes using a stable dose of insulin; patients with vitiligo or cured childhood asthma/allergy that does not require any intervention after adulthood; (8) Patients with a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation and a history of allogeneic bone marrow transplantation; (9) Patients with a history of interstitial lung disease (excluding radiation pneumonitis without hormone therapy),history of non-infectious pneumonia; (10) Patients with active tuberculosis infection found by medical history or CT examination, or patients with a history of active tuberculosis infection within 1 year prior to enrollment, or patients with a history of active tuberculosis infection more than 1 year ago who have not received standardized treatment; (11). Patients who have active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10^4 copies/mL), hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the lower limit of detection of the analytical method); (12) Patients with diseases that interfere with oral medication, including dysphagia, chronic diarrhea or Bowel obstruction; (13) Subjects known to have a history of psychotropic substance abuse, alcohol abuse or drug abuse; (14) Women during pregnancy or lactation; (15) Other conditions that may affect the safety or study compliance of the patients judged by the investigators, including but not limited to unstable heart disease, kidney disease, poorly controlled diabetes, emotional disorder, etc.

研究实施时间：

Study execute time：

从 From 2023-08-22 00:00:00至 To 2027-08-21 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-08-22 00:00:00 至 To 2025-08-21 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

29

Group：

experimental group

Sample size：

干预措施：

入组的受试者拟接受诱导治疗+同期放化疗和靶向治疗+辅助治疗，具体方案为：（1）诱导治疗阶段：3程尼妥珠单抗 (100mg，d0、d8，q3w) + 卡瑞利珠单抗 (200mg，d0，q3w) + GP (吉西他滨1000mg/m2，d1、d8 + 顺铂80mg/m2， d1，q3w)。（2）同期放化疗阶段（诱导治疗结束后3-6周开始）：顺铂100 mg/m2，d1，q3w，共2程，尼妥珠单抗 (200mg，d1，qw，共6程)，鼻咽及颈部根治性放疗。（3）辅助治疗阶段（同期放化疗结束后4-16周开始）：卡培他滨 (650mg/m2，bid，po)，直至直至出现以下情况之一：①患者出现进展，②出现不可忍受的毒副反应或死亡，③研究者决定停止治疗或患者撤回同意。辅助治疗最长1年。

干预措施代码：

Intervention：

Stage of induction traetment: 3 cycles of PD-1 inhibitor (200mg，d0，q3w) plus nimotuzumab (100mg，d0、d8，q3w) and chemotherapy (gemcitabine, 1000 mg/m2，d1、d8; cisplatin, 80mg/m2， d1，q3w), 21 days is a cycle. Stage of Concurrent treatment: cisplatin, 80mg/m2，d1，q3w, 2cycles; nimotuzumab 200mg，d1，qw; radiotherapy for nasopharynx and cervical metastatic lymph node. Stage of adjuvant treatment: Capecitabine (650mg/m2, take orally, two times every day) until 1 year or the end of the study.

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)：

 东莞 

Country：

China 

Province：

Guangdong 

City：

Dongguan 

单位(医院)：

南方医科大学第十附属医院(东莞市人民医院) 

单位级别：

三甲 

Institution
hospital：

The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital)

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

2年无进展生存率

指标类型：

主要指标

Outcome：

Two-year Progression-free Survival (PFS ) Rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存期

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：

2年无局部区域复发生存率

指标类型：

次要指标

Outcome：

Two-year locoregional recurrence free survival (LRRFS) 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：

2年无远处转移生存率

指标类型：

次要指标

Outcome：

Two-year distant metastasis-free survival (DMFS) 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：

诱导治疗后客观缓解率

指标类型：

次要指标

Outcome：

Objective response rate (ORR) after induction therapy

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

指标类型：

次要指标

Outcome：

Safety

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：

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：

标本中文名：

组织

组织：

Sample Name：

Tissue

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 18 岁 years
最大 Max age 65 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:

不公开/Private

盲法：

无

Blinding：

None

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）：

不共享

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

No sharing

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：

  2023-08-24 16:45:36