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Sintilimab plus gemcitabine combined cisplatin and local radiotherapy for primary tumor in the treatment of nasopharyngeal carcinoma with metastasis at first diagnosis:prospected, single-arm, phase II clinical trial
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注册号:

Registration number:

ChiCTR1900022683 

最近更新日期:

Date of Last Refreshed on:

2019-04-21 

注册时间:

Date of Registration:

2019-04-21 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

信迪利单抗联合吉西他滨加顺铂及原发灶局部放疗治疗初治远处转移鼻咽癌的前瞻性、单臂、II期临床研究 

Public title:

Sintilimab plus gemcitabine combined cisplatin and local radiotherapy for primary tumor in the treatment of nasopharyngeal carcinoma with metastasis at first diagnosis:prospected, 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:

信迪利单抗联合吉西他滨加顺铂及原发灶局部放疗治疗初治远处转移鼻咽癌的前瞻性、单臂、II期临床研究 

Scientific title:

Sintilimab plus gemcitabine combined cisplatin and local radiotherapy for primary tumor in the treatment of nasopharyngeal carcinoma with metastasis at first diagnosis:prospected, 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:

廖文军 

研究负责人:

陈念永 

Applicant:

Wenjun Liao 

Study leader:

Nianyong Chen 

申请注册联系人电话:

Applicant telephone:

+86 18280167590 

研究负责人电话:

Study leader's telephone:

+86 18980602053 

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:

363522967@qq.com 

研究负责人电子邮件:

Study leader's E-mail:

n_ychen@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:

四川成都国学巷37号 

研究负责人通讯地址:

四川成都国学巷37号 

Applicant address:

37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, China 

Study leader's address:

37 Guoxue Lane, Wuhou District, 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, Sichuan University 

是否获伦理委员会批准:

否 

Approved by ethic committee:

NO 

伦理委员会批件文号:

Approved No. of ethic committee:

 

伦理委员会批件附件:

Approved file of Ethical Committee:

批准本研究的伦理委员会名称:

 

Name of the ethic committee:

 

伦理委员会批准日期:

Date of approved by ethic committee:

2013-08-26 

伦理委员会联系人:

 

Contact Name of the ethic committee:

 

伦理委员会联系地址:

 

Contact Address of the ethic committee:

 

伦理委员会联系人电话:

Contact phone of the ethic committee:

 

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, Sichuan University 

研究实施负责(组长)单位地址:

四川成都国学巷37号 

Primary sponsor's address:

37 Guoxue Lane, 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):

华西医院

具体地址:

武侯区国学巷37号

Institution
hospital:

West China Hospital, Sichuan University

Address:

37 Guoxue Lane

经费或物资来源:

四川大学华西医院 

Source(s) of funding:

West China Hospital, Sichuan University  

研究疾病:

鼻咽癌 

Target disease:

nasopharyngeal carcinoma 

研究疾病代码:

 

Target disease code:

 

研究类型:

观察性研究 

Study type:

Observational study 

研究所处阶段:

II期临床试验 

Study phase:

研究目的:

探索信迪利单抗联合吉西他滨加顺铂及原发灶局部放疗治疗初治转移鼻咽癌的疗效和安全性 

Objectives of Study:

Exploring the efficacy and safety of Sintilimab combined with gemcitabine plus cisplatin and primary radiotherapy for nasopharyngeal carcinoma 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

非随机对照试验 

Study design:

Non randomized control 

纳入标准:

1)可以提供书面的知情同意书,并且理解和遵循研究要求和评估日程; 2)在签署知情同意书之日年龄在18-65岁; 3)组织学或细胞学检查确认为初治远处转移NPC(IVB期,AJCC第8版) 4)患者必须能够提供新鲜或存档的肿瘤组织(FFPE组织块或大约10 [≥6]张新鲜采集的、未染色的 FFPE 玻片)及其病理学报告。存档肿瘤组织必须是在研究筛查之前2年内采集的。如果没有充分的存档肿瘤组织,必须在基线时采集新鲜的肿瘤活检标本; 5)ECOG 体能状态≤ 1 ; 6)患者必须有≥1个可测量的病灶(按RECISTv1.1评估) ; 7)必须未曾接受抗肿瘤治疗; 8)预期寿命≥12 周; 9)器官功能充分,定义是在随机之前≤7 天内达到以下实验室检查值: 患者在筛选时采集血样之前14天内不得接受过输血或生长因子支持,指标要求达到如下: 白细胞绝对计数≥ 4x 109/L;绝对中性粒细胞计数≥ 1.5 x 109/L; 血小板≥ 100 x 109/L;血红蛋白≥ 90 g/L;国际标准化比值或凝 血酶原时间≤1.5 x 正常范围上限(ULN); 活化部分凝血活酶时间≤ 1.5 x ULN; 血清肌酐≤ 1.5 x ULN 或估计的肾小球滤过率≥ 60 mL/min/1.73 m2; 血清总胆红素≤1.5 x ULN(Gilbert 综合征患者若总胆红素< 3 x ULN 则可以入组) ;AST 和 ALT≤ 2.5 x ULN,如果患者存在肝转移,则这一标准为 AST 和 ALT ≤ 5 x ULN。 

Inclusion criteria

1. The patient has signed an informed consent form; 2. Aged 18 years to 65 years; 3. Pathologically confirmed as nasopharyngeal carcinoma; 4. nasopharyngeal carcinoma with distant metastasis at first diagnosis (IVB, AJCC version 8 staging); 5. patients must be able to provide fresh or archived tumor tissue (FFPE tissue blocks or approximately 10 [≥6] freshly harvested, unstained FFPE slides) and their pathology reports. Archived tumor tissue must be collected within 2 years prior to study screening. If tumor tissue is not adequately archived, fresh tumor biopsy specimens must be taken at baseline; 6. ECOG 0-1; 7. Patients must have ≥ 1 measurable lesion (assessed by RECISTv1.1); 8. In the newly diagnosed patient, no radiotherapy or chemotherapy was performed before the start of the clinical trial; 9. Life expectancy ≥12 weeks; 10. Patients should not receive blood transfusion or growth factor support within 14 days prior to blood sampling at screening. The indicator requirements are as follows: Absolute white blood cell count ≥ 4x 10^9/L; absolute neutrophil count ≥ 1.5 x 10^9/L; platelet ≥ 100 x 10^9/L; hemoglobin ≥ 90 g/L; international normalized ratio or prothrombin time ≤ 1.5 x normal range Upper limit (ULN); activated partial thromboplastin time ≤ 1.5 x ULN; serum creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2; serum total bilirubin ≤ 1.5 x ULN (Patients with Gilbert syndrome can be enrolled if total bilirubin < 3 x ULN is present; AST and ALT ≤ 2.5 x ULN, and if the patient has liver metastases, this standard is AST and ALT ≤ 5 x ULN. 

排除标准:

1)曾接受以PD-1或PD-L1为靶点的治疗; 2)有活动性自身免疫性疾病或者有自身免疫性疾病史但可能复发的患者 备注:以下疾病的患者不被排除,可以进入进一步筛选: a.受控的1型糖尿病;b.甲状腺机能减退(如果仅用激素替代疗法可以控制) c.受控的乳糜泻 d.无需全身治疗的皮肤病(例如白癜风,牛皮癣,脱发) e.其它任何在没有外部触发因素的情况下预期不会复发的疾病 3)在随机之前≤ 2 年内有任何活动性恶性肿瘤,除外本试验中正在研究的特定癌症以及已经治愈的局部复发癌症(例如切除的基底细胞或鳞状细胞性皮肤癌,浅表膀胱癌, 宫颈原位癌或乳腺癌) 4)在随机之前≤ 14 天内有任何需要用皮质类固醇全身治疗(剂量高于 10 mg/日的强的松或同类药物同等剂量)或其它免疫抑制剂治疗的病症; 5)随机之前≤14天存在未获得控制的糖尿病或尽管给予了标准药物治疗但仍>1级的钾、钠或校正钙水平的实验室检查异常或≥3 级低白蛋白血症; 6)有以下疾病史:间质性肺病、非感染性肺炎或不可控的疾病,包括肺纤维化、急性肺病、高血压等; 7)在随机之前或研究药物首次给药之前 14 天内曾发生需要给予系统抗生素、抗菌或抗病毒治疗的重度慢性或活动性感染(包括结核感染等) 8)已知有 HIV 感染史 9)未治疗的慢性乙型肝炎患者或慢性乙型肝炎病毒(HBV)DNA≥ 500 IU/mL的HBV携带者或活动性丙型肝炎病毒携带者(HCV)应排除。备注:非活动性乙型肝炎表面抗原(HBsAg)携带者,经治疗且稳定的乙型肝炎患者(HBV DNA < 500 IU/mL)和已治愈的丙肝患者可以入选; 10)在随机之前≤28 天内曾进行任何需要全麻的大手术 11)既往曾进行同种异体干细胞移植或者器官移植 12)有以下任何心血管风险因素: 在随机之前≤ 28 天内出现心源性胸痛,定义为限制日常生活的工具性活动的中度 疼痛 随机之前≤ 28 天内曾出现症状性肺栓塞 随机之前≤ 6 个月内曾发生急性心肌梗塞 在随机之前≤ 6 个月内有达到纽约心脏病协会 III 或 IV 级 在随机或研究药物首次给药前≤6个月内曾发生≥2级的室性心律失常 在随机之前或研究药物首次给药之前6个月内有脑血管意外病史 13)曾有对其它单克隆抗体严重超敏反应的病史; 14)对顺铂或吉西他滨有过敏反应史; 15)≥2 级周围神经疾病,根据 NCI CTCAE v5.0 标准定义 16)在随机之前≤ 4 周内曾接受活疫苗 17)不利于研究药物给药或影响药物毒性或AE的解读或导致研究执行的依从性不足或可能受到损害的基础医学状况(包括实验室异常)或酒精或药物的滥用或依赖; 18)同时参加另一项治疗性临床研究; 19)孕妇和哺乳期患者 

Exclusion criteria:

1. has received treatment targeting PD-1 or PD-L1; 2. Patients with active autoimmune diseases or who have a history of autoimmune diseases but may relapse; Remarks: Patients with the following diseases are not excluded and can be further screened: (1) controlled type 1 diabetes; (2) hypothyroidism (if only hormone replacement therapy can be used); (3) Controlled celiac disease; (4) Skin diseases that do not require systemic treatment (eg vitiligo, psoriasis, hair loss); (5) Any other disease that is expected to not recur without external triggers; 3. Any active malignancy within ≤ 2 years prior to randomization, except for the specific cancer being studied in this trial and the locally recurring cancer that has been cured (eg resected basal cells or squamous cell skin cancer, superficial bladder cancer, Cervical carcinoma in situ or breast cancer); 4. Any condition requiring systemic treatment with corticosteroids (dose higher than 10 mg/day of prednisone or equivalent) or other immunosuppressive agents within ≤ 14 days prior to randomization; 5. There is uncontrolled diabetes in ≤14 days before randomization or laboratory test abnormalities of >1 grade potassium, sodium or corrected calcium levels or ≥3 grade hypoalbuminemia despite standard drug therapy; 6. History of the following diseases: interstitial lung disease, non-infectious pneumonia or uncontrollable diseases, including pulmonary fibrosis, acute lung disease, hypertension, etc.; 7. Severe chronic or active infections (including tuberculosis infections, etc.) requiring systemic antibiotics, antibacterial or antiviral therapy before randomization or within 14 days prior to the first dose of study drug; 8. A history of HIV infection is known; 9. Untreated chronic hepatitis B patients or chronic hepatitis B virus (HBV) DNA ≥ 500 IU/mL HBV carriers or active hepatitis C virus carriers (HCV) should be excluded. Remarks: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA < 500 IU/mL) and cured hepatitis C patients can be enrolled; 10. Have any major surgery requiring general anesthesia ≤ 28 days before randomization; 11. Previous allogeneic stem cell transplantation or organ transplantation; 12. There are any cardiovascular risk factors: Cardiac chest pain occurs within ≤ 28 days before randomization and is defined as moderate pain that limits the instrumental activity of daily life; Symptomatic pulmonary embolism occurred ≤ 28 days before randomization; Acute myocardial infarction occurred ≤ 6 months before randomization; Meet New York Heart Association III or IV before ≤ 6 months before randomization; A ≥2 grade ventricular arrhythmia occurred within ≤6 months prior to the first dose of randomized or study drug; A history of cerebrovascular accidents before randomization or within 6 months prior to the first dose of study drug; 13. A history of severe hypersensitivity to other monoclonal antibodies; 14. a history of allergic reactions to cisplatin or gemcitabine; 15. ≥2 peripheral neuropathy, as defined by the NCI CTCAE v5.0 standard; 16. Received live vaccine within ≤ 4 weeks before randomization; 17. It is not conducive to the study drug administration or the interpretation of drug toxicity or AE or the underlying medical condition (including laboratory abnormalities) or the abuse or dependence of alcohol or drugs that leads to inadequate or potentially impaired research implementation; 18. Participate in another therapeutic clinical study at the same time; 19. pregnant and lactating patients. 

研究实施时间:

Study execute time:

From2019-05-01To 2022-05-31 

干预措施:

Interventions:

组别:

试验组

样本量:

32

Group:

Case series

Sample size:

干预措施:

信迪利单抗联合吉西他滨加顺铂及原发灶局部放疗

干预措施代码:

Intervention:

Sintilimab combined with gemcitabine plus cisplatin and primary radiotherapy

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):

成都 

Country:

China 

Province:

Sichuan 

City:

Chengdu 

单位(医院):

华西医院 

单位级别:

三级甲等 

Institution
hospital:

West China Hospital, Sichuan University  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

总生存率

指标类型:

主要指标 

Outcome:

overall survival

Type:

Primary 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:

无疾病进展生存时间

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:

不良反应

指标类型:

次要指标 

Outcome:

adverse events

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:

肿瘤组织

组织:

鼻咽部

Sample Name:

tumor tissue

Tissue:

nasopharyngeal

人体标本去向

使用后保存 

说明

Fate of sample:

Preservation after use 

Note:

标本中文名:

血液

组织:

血液

Sample Name:

blood

Tissue:

人体标本去向

使用后保存 

说明

Fate of sample:

Preservation 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 years
最大 Max age 65 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):

本实验属于单臂研究,不涉及随机,符合入排标准的将进行入组

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

This experiment belongs to the single-arm study and does not involve randomization.

盲法:

N/A

Blinding:

N/A

试验完成后的统计结果(上传文件):

Calculated Results ater
the Study Completed(upload file):

原始数据公开时间:

The time of sharing IPD:

Real time access

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):

临床试验结束后半年内共享;ResMan共享平台

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

within half year after clinical trial finished; ResMan platform

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:

ResMan

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

ResMan

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2019-04-21
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