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编码新生抗原的mRNA个性化肿瘤疫苗治疗晚期恶性实体瘤
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注册号:

Registration number:

ChiCTR1900023000 

最近更新日期:

Date of Last Refreshed on:

2019-05-06 

注册时间:

Date of Registration:

2019-05-06 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

编码新生抗原的mRNA个性化肿瘤疫苗治疗晚期恶性实体瘤 

Public title:

Personalized Cancer Vaccine mRNA Encoding Neoantigen in the Treatment of Advanced Malignant Solid Tumors  

注册题目简写:

PCV-NEO-ONC-RNA 

English Acronym:

PCV-NEO-ONC-RNA 

研究课题的正式科学名称:

编码新生抗原的mRNA个性化肿瘤疫苗治疗晚期恶性实体瘤的临床研究 

Scientific title:

The clinical trial on personalized mRNA tumor vaccine in the treatment of advanced malignant solid tumors 

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:

于波 

研究负责人:

李进 

Applicant:

Yu Bo 

Study leader:

Li Jin 

申请注册联系人电话:

Applicant telephone:

+86 13818425486 

研究负责人电话:

Study leader's telephone:

+86 021-38804518-22132 

申请注册联系人传真 :

Applicant Fax:

 

研究负责人传真:

Study leader's fax:

+86 021-50613552 

申请注册联系人电子邮件:

Applicant E-mail:

yubo@stemirna.com 

研究负责人电子邮件:

Study leader's E-mail:

li.jin@csco.org.cn 

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:

上海市浦东新区川桥路1295号2幢603室 

研究负责人通讯地址:

上海市浦东新区云台路1800号5号门8楼 

Applicant address:

1295 Chuanqiao Road, Pudong New District, Shanghai, China 

Study leader's address:

8th Floor, Gate 5, 1800 Yuntai Road, Pudong District, Shanghai, 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:

斯微(上海)生物科技有限公司 

Applicant's institution:

Stemirna Therapeutics LLC 

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:

2018临审第(042)号 

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:

上海市东方医院药物临床试验伦理委员会 

Name of the ethic committee:

EC of clincial trial in hospital  

伦理委员会批准日期:

Date of approved by ethic committee:

 

伦理委员会联系人:

鲍思蔚 

Contact Name of the ethic committee:

Siwei Bao 

伦理委员会联系地址:

上海市浦东新区云台路1800号 

Contact Address of the ethic committee:

1800 Yuntai Road, Pudong District, Shanghai, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 021-38804518-22198 

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:

同济大学附属东方医院 

Primary sponsor:

Dongfang Hospital Affiliated to Shanghai Tongji University 

研究实施负责(组长)单位地址:

上海市浦东新区即墨路150号 

Primary sponsor's address:

150 Jimo Road, Pudong New Area, Shanghai, 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):

上海市

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

同济大学附属东方医院

具体地址:

上海市浦东新区即墨路150号

Institution
hospital:

Dongfang Hospital Affiliated to Shanghai Tongji University

Address:

150 Jimo Road, Pudong New Area, Shanghai

经费或物资来源:

企业资助 

Source(s) of funding:

Enterprise funding 

研究疾病:

晚期恶性实体瘤 

Target disease:

Advanced Malignant Solid Tumors  

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:

I期临床试验 

Study phase:

研究目的:

探索编码新生抗原的mRNA个性化肿瘤疫苗治疗晚期恶性实体瘤的安全性和疗效 

Objectives of Study:

To explore the safety and efficacy of personalized cancer vaccine encoding neoantigen in the treatment of advanced malignant solid tumors.  

药物成份或治疗方案详述:

个性化mRNA肿瘤疫苗 

Description for medicine or protocol of treatment in detail:

personalized mRNA cancer vaccine 

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

受试者必须满足以下所有入选标准才可入组本研究: 1)年龄18~80周岁(包括两端),性别不限; 2)经病理组织学或细胞学确诊,标准治疗失败或无标准治疗的转移性或局部晚期恶性实体肿瘤患者; 3)根据实体瘤的疗效评价标准(RECIST)1.1版,至少有一个可测量肿瘤病灶; 4)无严重的血液系统、肝肾功能异常:淋巴细胞数≥0.8×109/L,绝对中性粒细胞数目≥1.5×109/L,血红蛋白≥9g/dL,血小板≥75×109/L;ALT≤3倍ULN,AST≤3倍ULN,血肌酐≤1.5倍ULN;活化部分凝血活酶时间(APTT)≤1.5倍ULN,凝血酶原时间(PT)≤1.5倍ULN,国际标准化比值(INR)≤1.5倍ULN; 5)ECOG评分0~1; 6)有生育能力的患者必须同意在试验期间和末次治疗后至少12周内使用可靠的避孕方法(激素或屏障法或禁欲); 7)患者本人自愿参加并书面签署知情同意书。 

Inclusion criteria

1. Aged 18 to 80 years old male and female; 2. Patients with metastatic or locally advanced malignant solid tumors diagnosed by histopathology or cytology, standard treatment failure or no standard treatment; 3. According to the solid tumor evaluation criteria (RECIST) version 1.1, at least one measurable tumor lesion; 4. normal blood system, liver and kidney function: lymphocyte number ≥ 0.8 × 10^9/L, absolute neutrophil number ≥ 1.5 × 10^9/L, hemoglobin ≥ 9g/dL, platelets ≥ 75 × 10^9/L; ALT ≤ 3 times ULN, AST ≤ 3 times ULN, serum creatinine ≤ 1.5 times ULN; activated partial thromboplastin time (APTT) ≤ 1.5 times ULN, prothrombin time (PT) ≤ 1.5 times ULN, international normalized ratio (INR) ) ≤ 1.5 times ULN; 5. ECOG score 0~1; 6. Patients with fertility must agree to use reliable methods of contraception (hormone or barrier or abstinence) during the trial and at least 12 weeks after the last treatment; 7. The patient himself voluntarily participates and signs the informed consent form in writing. 

排除标准:

具有以下任何一项的受试者不能入组本研究: 1)既往有生物药物过敏史者; 2)处于妊娠期或哺乳期者; 3)预计生存期小于6个月者; 4)需全身治疗的活动性感染或无法控制的感染; 5)肿瘤突变负荷(TMB)小于2.0/Mb或新生抗原负荷(TNB)小于0.5/Mb或预测的新生抗原数量小于3个者; 6)首次给予mRNA肿瘤疫苗治疗前28天内接受了化疗、生物治疗、放射治疗、内分泌治疗、小分子靶向治疗等抗肿瘤治疗(其中氟尿嘧啶类的口服药物,如替吉奥、卡培他滨,最后1次口服药物与首次给予mRNA肿瘤疫苗治疗的间隔时间为至少14天即可),或其他试验药物治疗,或手术(不含诊断性活检)者; 7)既往抗肿瘤治疗的不良反应尚未恢复到CTCAE 4.03等级评价≤1级(脱发除外); 8)有严重心脑血管疾病史,包括但不限于需要临床干预的室性心律失常;6个月内有急性冠脉综合征、心肌梗死、充血性心力衰竭、脑卒中或其他III级及以上心血管事件;美国纽约心脏病协会(NYHA)心功能分级≥II级或左室射血分数(LVEF)<50%;经标准治疗仍控制不良的高血压(收缩压>150mmHg,舒张压>90mmHg); 9)具有临床症状的中枢神经系统转移和/或癌性脑膜炎者(脑转移稳定的患者可入组),临床怀疑中枢神经系统或者软脑膜转移者需CT /MRI检查予以排除; 10)目前存在活动性溃疡、消化道出血的患者; 11)有临床确诊的自身免疫性疾病者; 12)有HIV感染者;有急性EBV或者CMV病毒感染者; 13)乙肝病毒有活跃复制的患者(DNA>500 cps/mL),丙型肝炎患者; 14)既往接受过同种异体骨髓移植者; 15)免疫抑制的受试者,包括已知的免疫缺陷者;当前正在全身性使用类固醇药物者(近期或者目前使用吸入性类固醇者除外); 16)皮肤疾病(如银屑病)可能会影响皮内注射疫苗进入目标区域者; 17)已知有酒精或药物依赖者; 18)研究者评估认为存在可能妨碍受试者全程参与本研究的病史或疾病、治疗或实验值异常值,或参与研究不符合受试者最大利益。 

Exclusion criteria:

1. Those who have had a history of allergies to biopharmaceuticals; 2. Those who are pregnant or breastfeeding; 3. Those with a predicted survival period of less than 6 months; 4. active or uncontrolled infections requiring systemic treatment; 5. Tumor mutation burden (TMB) < 2.0/Mb or tumor neoantigen burden (TNB) <0.5/Mb or predicted number of neoantigens is less than 3 6. Anti-tumor treatments such as chemotherapy, biotherapy, radiation therapy, endocrine therapy, and small molecule targeted therapy were administered within 28 days prior to the first administration of mRNA tumor vaccine (in which fluorouracil oral drugs such as tigio, capecitabine, and finally 1 time oral medication and the first dose of mRNA tumor vaccine treatment at least 14 days), or other test drug treatment, or surgery (excluding diagnostic biopsy); 7. Adverse reactions to previous anti-tumor treatment have not been restored to CTCAE 4.03 grade evaluation ≤ 1 (except for hair loss); 8. History of severe cardiovascular and cerebrovascular diseases, including but not limited to ventricular arrhythmias requiring clinical intervention; acute coronary syndrome, myocardial infarction, congestive heart failure, stroke or other grade III and above cardiovascular disease within 6 months Event; New York Heart Association (NYHA) cardiac function classification ≥ II or left ventricular ejection fraction (LVEF) < 50%; hypertension still controlled by standard treatment (systolic blood pressure > 150mmHg, diastolic blood pressure > 90mmHg); 9. Patients with clinically symptomatic central nervous system metastasis and / or cancerous meningitis (patients with stable brain metastases can be enrolled), clinically suspected central nervous system or pia mater transfer should be excluded by CT / MRI; 10. Patients with active ulcers and gastrointestinal bleeding; 11. Those with clinically diagnosed autoimmune diseases; 12. those with HIV infection; those with acute EBV or CMV virus infection; 13. Patients with active replication of hepatitis B virus (DNA > 500 cps/mL), patients with hepatitis C; 14. Those who have received allogeneic bone marrow transplants in the past; 15. Subjects with immunosuppression, including known immunodeficiency; those currently on systemic use of steroids (except those who have recently or recently used inhaled steroids); 16. Skin diseases (such as psoriasis) may affect the intradermal injection of vaccine into the target area; 17. those who are known to have alcohol or drug dependence; 18. The investigator assessed that there were abnormalities in the history or disease, treatment, or experimental values that might prevent the subject from participating in the study throughout the study, or that participating in the study did not meet the best interests of the subject. 

研究实施时间:

Study execute time:

From2019-05-01To 2021-05-31 

征募观察对象时间:

Recruiting time:

From2019-05-01To 2020-05-31 

干预措施:

Interventions:

组别:

单组

样本量:

24

Group:

Case series

Sample size:

干预措施:

个性化mRNA肿瘤疫苗

干预措施代码:

Intervention:

personalized mRNA cancer vaccine

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

上海 

市(区县):

 

Country:

China 

Province:

Shanghai 

City:

 

单位(医院):

同济大学附属东方医院 

单位级别:

三级甲等 

Institution
hospital:

Dongfang Hospital Affiliated to Shanghai Tongji University  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

抗新生抗原特异的CD4+和CD8+ T淋巴细胞反应

指标类型:

主要指标 

Outcome:

Specific CD4 + and CD8 + T lymphocyte responses to neoantigen

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

胸腹盆部位 CT/MRI检查

指标类型:

次要指标 

Outcome:

CT/MRI examination of thoracic, abdominal and pelvic region

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

全面体格检查

指标类型:

次要指标 

Outcome:

Comprehensive physical examination

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

生命体征

指标类型:

次要指标 

Outcome:

Vital signs

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

主诉症状

指标类型:

次要指标 

Outcome:

Complaint symptom

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血常规

指标类型:

次要指标 

Outcome:

routine blood test

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

尿常规

指标类型:

次要指标 

Outcome:

Urine routine test

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血生化

指标类型:

次要指标 

Outcome:

blood biochemistry

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

凝血四项

指标类型:

次要指标 

Outcome:

Four items of blood coagulation

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

心电图

指标类型:

次要指标 

Outcome:

electrocardiogram

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 years
最大 Max age 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):

不适用

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

N/A

盲法:

N/A

Blinding:

N/A

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):

不适用

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

NA

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:

CRF

数据与安全监察委员会:

Data and Safety Monitoring Committee:

有/Yes

注册人:

Name of Registration:

 2019-05-06
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