ChiCTR2300073467 版本V1.0 版本创建时间2023/07/11 17:48:50 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：

 ChiCTR2300073467 

最近更新日期：

Date of Last Refreshed on：

 2023-07-11 17:48:31 

注册时间：

Date of Registration：

 2023-07-11 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

PD-1单抗联合尼妥珠单抗和吉西他滨加顺铂化疗一线治疗初诊转移性鼻咽癌：一项单臂、前瞻性的II期临床研究

Public title：

PD-1 inhibitor combined with nimotuzumab and gemcitabine plus cisplatin for the first-line treatment of newly diagnosed metastatic nasopharyngeal carcinoma: a single arm, phase II clinical study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

PD-1单抗联合尼妥珠单抗和吉西他滨加顺铂化疗一线治疗初诊转移性鼻咽癌：一项单臂、前瞻性的II期临床研究

Scientific title：

PD-1 inhibitor combined with nimotuzumab and gemcitabine plus cisplatin for the first-line treatment of newly diagnosed metastatic nasopharyngeal carcinoma: a single arm, phase II clinical study

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：

 +86 198 7863 6690

研究负责人电话：

Study leader's
telephone：

+86 186 2758 5860

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：

 zhongguihua1995@163.com

研究负责人电子邮件：

Study leader's E-mail：

 zhigangliu1983@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：

广东省东莞市万江街道万道路78号

研究负责人通讯地址：

广东省东莞市万江街道万道路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：

东莞市人民医院

Applicant's institution：

Dongguan people's hospital

研究负责人所在单位：

东莞市人民医院

Affiliation of the Leader：

Dongguan people's hospital

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：

 KYKT2023-024

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：

 2023-06-05 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：

东莞市人民医院

Primary sponsor：

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)：

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：

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

研究疾病：

鼻咽癌  

Target disease：

nasopharyngeal 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、主要目的：评价 PD-1 单抗联合尼妥珠单抗和吉西他滨加顺铂化疗一线治疗初诊转移性鼻咽癌的疗效（包括无进展生存期、总体生存期、客观缓解率和疾病控制率）和安全性。 2、次要目的：探索初诊转移性鼻咽癌潜在遗传生物标记物及临床治疗疗效评价的相关性，探究免疫相关生物标志物和分子的表达水平及其对预后的预测价值。  

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 combined with nimotuzumab and gemcitabine plus cisplatin for the first-line treatment of newly diagnosed metastatic nasopharyngeal carcinoma. 2. Secondary objective: to explore the correlation between the potential genetic biomarker of newly diagnosed metastatic nasopharyngeal carcinoma and the clinical treatment efficacy, and to explore the expression level of immune related biomarkers and molecules 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）经组织学或细胞学确诊为鼻咽癌； （2）经完整的影像学评估，初诊或复发的鼻咽癌患者的临床分期为IVb期（AJCC 第8版），且经经验丰富的临床医师判断不可局部治疗（局部治疗包括手术、射频消融、经导管动脉化疗栓塞、放疗等，除外骨转移患者的局部姑息性放疗）； （3）患者未因复发或转移接受任何抗肿瘤治疗，包括放疗、化疗、靶向治疗和免疫治疗等（接受新辅助化疗、辅助化疗或根治性同步放化疗后疾病进展超过6个月的患者除外）； （4）根据RECIST 1.1标准，至少有一个可测量病灶，可测量病灶应未接受过放疗等局部治疗； （5）年龄为18-75岁之间； （6）ECOG PS评分0-1分； （7）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ANC≥1.5×109 /L；血小板计数PLT≥100×109 /L；血红蛋白HB≥90 g/L； b. 总胆红素 ≤ 1.5×ULN； c. 无肝脏转移者：谷丙转氨酶ALT、谷草转氨酶AST≤2.5×ULN；如存在肝脏转移，则ALT和AST≤5×ULN； d. 血清肌酐≤1.5×ULN，或肌酐清除率≥50 mL/min（根据 Cockcroft-Gault 公式计算）； （8）预期寿命≥12周； （9）女性受试者应为接受手术绝育后或绝经后患者，或非手术绝育或育龄女性及入组的性活跃期的男性同意在研究期间和研究结束后6个月内采取至少一种医学上认可的避孕措施（如宫内节育器、口服避孕药和避孕套）；非手术绝育的育龄期女性受试者还必须在入组前7天内血清或尿液妊娠试验呈阴性，且必须处于非哺乳期。 （10）受试者自愿加入本研究，签署知情同意书，自觉依从性好，配合随访。

Inclusion criteria

(1) Patients pathologically diagnosed with nasopharyngeal carcinoma; (2) Patients newly diagnosed with advanced nasopharyngeal carcinoma at Stage IVb defined by the American Journal of Critical Care (AJCC) staging system (the 8th edition), or relapsed nasopharyngeal carcinoma not suitable for local treatment. Local treatment mainly refers to anti-tumor treatment-related measures, including surgery, radiofrequency ablation, transcatheter arterial chemoembolization (TACE), radiotherapy (except for radiotherapy at local appropriate doses for the relief of symptoms that does not affect blood pictures in patients with bone metastases); (3) Patients who have not received chemotherapy for relapsed or metastatic nasopharyngeal carcinoma (except for patients whose disease progressed more than 6 months after the receipt of neoadjuvant chemotherapy, adjuvant chemotherapy, or radical concurrent chemoradiotherapy); (4) 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; (5) Aged ≥ 18 years and ≤ 75 years; (6) The Eastern Cooperative Oncology Group (ECOG) score: 0~1 point; (7) 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; Platelet count ≥ 100 × 10^9/L; Hemoglobin ≥ 90 g/L; b. Total bilirubin ≤ 1.5 × ULN, c. ALT and/or AST ≤ 2.5 × ULN; if there is liver metastasis, ALT and/or AST ≤ 5 × ULN; d. Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min (Cockcroft-Gault); (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 (IUD, birth control pills or condoms) during the study treatment, period, at least 3 months after the last dose of camrelizumab/placebo, 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）可接受手术、根治性放疗或根治性放化疗等根治性治疗的局部晚期患者； （3）有临床症状的中枢神经系统转移，如脑水肿和需要激素干预，或脑转移进展的患者。既往接受过脑或脑膜转移治疗，但MRI和临床表现均稳定（不需要> 10 mg/day强的松或同等剂量的激素治疗）的患者除外。 （4） 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； （5）同时参加另一临床研究的受试者，除外观察性研究； （6）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； （7）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； （8）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）； （9）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； （10）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； （11）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； （12）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； （13）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）； （14）会干扰口服药物的疾病，包括吞咽困难、慢性腹泻或肠梗阻； （15）已知有精神类药物的滥用、酗酒及吸毒史； （16）怀孕或哺乳期妇女； （17）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, gemcitabine, cisplatin and capecitabine or its components; (2) Locally advanced patients who can receive radical treatment such as surgery, radical radiotherapy or radical radiochemotherapy; (3) Patients with clinically symptomatic central nervous system metastases such as cerebral edema and requiring hormone intervention, or progression of brain metastases. Patients who have previously received brain or meningeal metastasis treatment, if they are stable both as shown by MRI and clinically (do not require > 10 mg/day prednisone or equivalent dose of hormone therapy), can be included; (4) Patients previously 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.); (5) Patients who participated in another clinical study at the same time, except for the observational study; (6) 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; (7) 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; (8) 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); (9) 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; (10) 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; (11) Patients with a history of interstitial lung disease (excluding radiation pneumonitis without hormone therapy),history of non-infectious pneumonia; (12) 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; (13). 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); (14) Patients with diseases that interfere with oral medication, including dysphagia, chronic diarrhea or Bowel obstruction; (15) Subjects known to have a history of psychotropic substance abuse, alcohol abuse or drug abuse; (16) Women during pregnancy or lactation; (17) 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 2023-06-05 00:00:00至 To 2026-06-04 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-07-15 00:00:00 至 To 2025-06-04 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 26

Group：

experimental group

Sample size：

干预措施：

第一阶段为PD-1单抗+尼妥珠单抗+化疗联合治疗阶段，21天为1周期，共4-6周期，具体方案为：PD-1单抗（由研究者选择，包括但不限于卡瑞利珠单抗、特瑞普利单抗、替雷利珠单抗、信迪利单抗等），静脉滴注，第0天（即化疗前1天打）；尼妥珠单抗，静脉滴注，第0天（即化疗前1天打）；化疗：吉西他滨，静脉滴注，第1、8天，(1000mg/m2) + 顺铂，静脉滴注，第1天(80mg/m2)。（2）第二阶段为维持治疗阶段，具体方案为：PD-1单抗（由研究者选择，包括但不限于卡瑞利珠单抗、特瑞普利单抗、替雷利珠单抗、信迪利单抗等）静脉滴注 (d1，q3w)；卡培他滨 (650mg/m2，口服，bid) ；PD-1单抗和卡培他滨需一直给药，直至研究结束。

干预措施代码：

Intervention：

The first stage is the PD-1 inhibitor plus nimotuzumab and chemotherapy combination treatment, 21 days is a cycle, a total of 4-6 cycles, and the specific discription is: PD-1 inhibitor (selected by the researchers, including but not limited to Camrelizumab, Toripalimab, Tislelizumab, Sintilimab, etc.), intravenous infusion, day 0 (one day before chemotherapy); Nimotuzumab, intravenous infusion, on day 0 (one day before chemotherapy); Chemotherapy: Gemcitabine, intravenous infusion, day 1 and 8, (1000mg/m2), Cisplatin, intravenous infusion, day 1 (80mg/ m2). The second stage is the maintenance treatment, and the specific discription is: PD-1 inhibitor (selected by the researchers, including but not limited to Camrelizumab, Toripalimab, Tislelizumab, Sintilimab, etc.), intravenous infusion (day 1, every 3 weeks); Capecitabine (650mg/m2, take orally, two times every day); PD-1 inhibitor and Capecitabine should be administered until 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)：

 东莞市人民医院 

单位级别：

 三甲 

Institution
hospital：

Dongguan People's Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

1年无进展生存率

指标类型：

主要指标

Outcome：

One-year 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：

客观缓解率

指标类型：

次要指标

Outcome：

Objective Response Rate (ORR)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病控制率

指标类型：

次要指标

Outcome：

Disease Control Rate (DCR)

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：

组织切片或组织石蜡标本

组织：

Sample Name：

Tissue section or tissue paraffin specimen

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 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：

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

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）：

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：

  2023-07-11 17:48:31