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：	ChiCTR2100045146
最近更新日期： Date of Last Refreshed on：	2021-11-08 16:51:07
注册时间： Date of Registration：	2021-04-07 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	评估BM201注射液联合放疗在晚期恶性实体肿瘤患者中的安全性、耐受性与抗肿瘤作用的0期开放、单中心临床研究
Public title：	Phase 0 open, single-center clinical study to evaluate the safety, tolerability and anti-tumor effects of BM201 injection combined with radiotherapy in patients with advanced malignant solid tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	评估BM201注射液联合放疗在晚期恶性实体肿瘤患者中的安全性、耐受性与抗肿瘤作用的0期开放、单中心临床研究
Scientific title：	Phase 0 open, single-center clinical study to evaluate the safety, tolerability and anti-tumor effects of BM201 injection combined with radiotherapy in patients with 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：	陈为谦	研究负责人：	纪建松
Applicant：	Chen Weiqian	Study leader：	Ji Jiansong
申请注册联系人电话： Applicant telephone：	+86 15157886778	研究负责人电话： Study leader's telephone：	+86 13857088508
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：	ls2119088@126.com	研究负责人电子邮件： Study leader's E-mail：	jjstcty@sina.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：	浙江省丽水市括苍路289号	研究负责人通讯地址：	浙江省丽水市括苍路289号
Applicant address：	289 Kuocang Road, Lishui, Zhejiang.	Study leader's address：	289 Kuocang Road, Lishui, Zhejiang.
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：	丽水市中心医院
Applicant's institution：	Lishui Central Hospital
研究负责人所在单位：	丽水市中心医院
Affiliation of the Leader：	Lishui Central 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：	2021-17	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：	丽水市中心医院医学伦理委员会
Name of the ethic committee：	Ethics Committee of Lishui Central Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2021-03-02 00:00:00
伦理委员会联系人：	徐民
Contact Name of the ethic committee：	Xu Min
伦理委员会联系地址：	浙江省丽水市括苍路289号
Contact Address of the ethic committee：	289 Kuocang Road, Lishui, Zhejiang.
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：

丽水市中心医院

Primary sponsor：

Lishui Central Hospital

研究实施负责（组长）单位地址：

浙江省丽水市括苍路289号

Primary sponsor's address：

289 Kuocang Road, Lishui City

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	江苏	市(区县)：	苏州
Country：	China	Province：	Jiangsu	City：	Suzhou
单位(医院)：	苏州大学	具体地址：	工业园区仁爱路199号
Institution hospital：	Soochow University	Address：	199 Ren'ai Road, Industrial Park

国家：	Soochow University	省(直辖市)：	江苏	市(区县)：	苏州
Country：	China	Province：	Jiangsu	City：	Suzhou
单位(医院)：	苏州百迈生物医药有限公司	具体地址：	工业园区星湖街218号
Institution hospital：	Suzhou Innovative Biomaterials & Pharmaceutics Co., Ltd.	Address：	218 Xinghu Street, Industrial Park

经费或物资来源：

自筹

Source(s) of funding：

self-funded

研究疾病：

肿瘤

Target disease：

Tumor

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：

探索性研究/预试验

Study phase：

0

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的：评价BM201注射液瘤内注射联合放疗在标准治疗失败或不能耐受的晚期实体瘤患者中的安全性和耐受性；次要目的：评价BM201注射液瘤内注射联合放疗在标准治疗失败或不能耐受的晚期实体瘤患者中的药代动力学（PK）特征；初步评价BM201注射液瘤内注射联合放疗在标准治疗失败或不能耐受的晚期实体瘤患者中的抗肿瘤作用（ORR、PFS）。探索性目的：探索外周血淋巴细胞亚群（CD3+T细胞、CD4+T细胞、CD8+T细胞、Treg细胞、NK细胞）、细胞因子（α-干扰素[IFN-α]、肿瘤坏死因子α[TNF-α]、白介素-6[IL-6]和白介素-12[IL-12]）水平的变化；探索外周血免疫细胞中PD-1、PD-L1、CTLA-4的表达变化情况。

Objectives of Study：

Main purpose: To evaluate the safety and tolerability of intratumoral injection of BM201 injection combined with radiotherapy in patients with advanced solid tumors who have failed or cannot tolerate standard treatment; Secondary purpose: To evaluate the pharmacokinetic (PK) characteristics of BM201 injection intratumor injection combined with radiotherapy in patients with advanced solid tumors who have failed or cannot tolerate standard treatment;To preliminarily evaluate the anti-tumor effects (ORR, PFS) of BM201 injection combined with intratumoral injection of radiotherapy in patients with advanced solid tumors who have failed or cannot tolerate standard treatment. Exploratory purpose: Explore peripheral blood lymphocyte subsets (CD3 + T cells, CD4 + T cells, CD8 + T cells, Treg cells, NK cells), cytokines (α-interferon [IFN-α], tumor necrosis factor α [TNF-α], interleukin-6 [IL-6] and interleukin-12 [IL-12]) changes in levels;Explore the expression changes of PD-1, PD-L1, and CTLA-4 in peripheral blood immune cells.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1.Male or female patients, aged 18 to 75 years;
2.Patients with advanced malignant tumors that have been clearly diagnosed by pathology and/or cytology, such as liver cancer, ovarian cancer, prostate cancer, etc.
3.Patients with advanced solid tumors who have failed or cannot tolerate standard treatment;
4.ECOG score 02 points;
5.The expected survival period is more than 3 months;
6.According to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1 version), the patient has at least one measurable or evaluable tumor lesion with the longest diameter at baseline >= 10mm (if it is a lymph node, the short diameter is required to be >= 15mm). The lesion is suitable for intratumoral injection (the length of the lesion is at least greater than or equal to 10 mm);
7.The patient should have sufficient bone marrow reserve function, or no liver and kidney coagulation dysfunction, laboratory test values must meet the following conditions:
(1) Absolute neutrophil count > 1.5 x 10^9/L, and white blood cell count > 3 x 10^9/L;
(2) Platelet count > 80 x 10^9/L;
(3) Hemoglobin > 90 g/L;
(4) Serum creatinine < 1.5 x upper limit of normal (ULN) and creatinine clearance calculated by Cockroft-Gault formula > 30 mL/min;
(5) If there is no confirmed liver metastasis, AST, ALT < 2.5x ULN; if there is confirmed liver metastasis, AST, ALT < 5 x ULN;
(6) If there is no liver metastasis, total bilirubin is less than 1.5 x ULN; if there is liver metastasis or Gilbert syndrome (high indirect bilirubinemia), total bilirubin is less than 3 x ULN;
(7) International normalized ratio (INR)  < 1.5, and activated partial prothrombin time (APTT) < 1.5 x ULN;
8.The patient has no brain metastases (except for patients with asymptomatic brain metastases, or patients who have been treated with brain metastases but have been treated with stable disease for more than 4 weeks);
9.The patient voluntarily signs the informed consent form, and the expected compliance is good.

排除标准：

1.已知或怀疑对研究药物成份或其类似物过敏；
2.患者存在任何不稳定或可能影响其安全性或研究依从性的其他任何疾病或医学状态，任何严重或未控制的系统性疾病，包括严重心脏病、脑血管病、未控制的糖尿病、未控制的高血压、严重感染、活动性消化道溃疡、免疫功能异常等。
3.符合下列任一条件的心脑血管疾病/症状/指征：
(1)平均静息QTc>470 ms（经过校正的QT间期[通过Fridericia公式校正])，3次ECG QTc的平均值，QT间期测量应从QRS复合波起始至T波结束）；
(2)任何有临床意义的重要的静息ECG在节律、传导或形态方面的异常，如完全性左束支传导阻滞、2度和3度的心脏传导阻滞、PR间期> 250 ms等；
(3)任何增加QTc延长或心律失常风险的因素，如心力衰竭、低钾血症、先天性长QT综合征、长QT综合征家族史，或在40岁以下一级亲属中不明原因的猝死，或任何已知可延长QT间期的合并用药；
(4)左室射血分数（LVEF）<50%；
(5)既往有心肌收缩力下降的病史，且在研究给药前6个月内出现过相关症状者：如慢性充血性心力衰竭、肺水肿或心脏射血分数下降等；
(6)既往有急慢性心脑血管病史，且在研究给药前6个月内出现过相关症状者：如心肌梗塞，重度或不稳定型心绞痛，脑梗塞，脑出血，或短暂性脑缺血发作等；
4.罹患其他恶性肿瘤或有其他恶性肿瘤病史者，除外既往已得到有效控制的、非侵袭性的、5年无复发转移的皮肤基底细胞癌或鳞状细胞癌，宫颈原位癌和乳腺导管癌；
5.病灶无法满足瘤体内注射2 mL容量的要求；
6.对于育龄期女性（绝经后女性必须已绝经至少12个月才能被认为无生育能力）在研究用药瘤内注射前7天内血清妊娠试验检查结果为阳性者；或经研究者判断，在研究期间及研究药物最后一次给药后3个月内，有意愿怀孕、哺乳，或不愿采用有效避孕措施者（包括男性受试者及其育龄女性配偶）；
7.研究药物首次给药前4周内
(1)接受过化疗、放疗、生物/靶向药物治疗、免疫药物治疗等其他抗肿瘤治疗；
(2)接受过大手术；
(3)参加过其他临床试验，采用了或正在采用其他试验性药物治疗（非干预性药物临床试验除外）；
8.可能增加研究和研究用药风险、或者可能会干扰研究结果的其他重度、急性、或慢性的临床或精神疾病或实验室异常情况；
9.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，但以下疾病的患者不被排除，可以进一步筛选：a. I 型糖尿病 b.甲状腺功能减退（如果仅用激素替代疗法可以控制）c.受控制的乳糜泻 d.无需全身治疗的皮肤病（例如白癜风、牛皮癣、脱发）e.其他任何在没有外部触发因素的情况下不会再次发生的疾病；
10.活动性人类免疫缺陷病毒（HIV）、梅毒、丙型肝炎病毒（HCV）或乙型肝炎病毒（HBV）感染者。
活动性HBV，HCV和HIV感染定义为：
(1)HBsAg阳性且HBV DNA ≥1000 cps/mL（或200 IU/mL）；
(2)抗-HCV抗体且HCV RNA阳性；
(3)HIV 抗体阳性；
11.经研究者判断放疗不能耐受或有放疗禁忌症者；
12.不能耐受BM201注射液的局部注射；
13.研究者认为患者有任何原因不适宜参加本试验。

Exclusion criteria：

1.Known or suspected allergies to study drug ingredients or their analogs;
2.The patient has any other diseases or medical conditions that are unstable or may affect their safety or research compliance, any serious or uncontrolled systemic diseases, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, and uncontrolled diabetes. Controlled high blood pressure, severe infections, active peptic ulcers, abnormal immune function, etc.
3.Cardiovascular and cerebrovascular diseases/symptoms/indications that meet any of the following conditions:
(1)Average resting QTc > 470 ms (corrected QT interval [corrected by Fridericia formula]), the average of 3 ECG QTc, the QT interval measurement should be from the beginning of the QRS complex to the end of the T wave);
(2)Any clinically important resting ECG abnormalities in rhythm, conduction or morphology, such as complete left bundle branch block, 2 and 3 degree heart block, PR interval > 250 ms Wait;
(3)Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in first-degree relatives under 40 , Or any combination drug that is known to prolong the QT interval;
(4)Left ventricular ejection fraction (LVEF) < 50%;
(5)Those who have a history of decreased myocardial contractility and have had related symptoms within 6 months before study administration: such as chronic congestive heart failure, pulmonary edema, or decreased cardiac ejection fraction;
(6)Those who have a history of acute and chronic cardiovascular and cerebrovascular diseases and have related symptoms within 6 months before the study administration: such as myocardial infarction, severe or unstable angina, cerebral infarction, cerebral hemorrhage, or transient brain deficiency Blood attack, etc.;
4.Suffer from other malignant tumors or have a history of other malignant tumors, except for those who have been effectively controlled, non-invasive, basal cell carcinoma of the skin or squamous cell carcinoma with no recurrence and metastasis for 5 years, carcinoma in situ of the cervix and breast ducts cancer;
5.The lesion cannot meet the requirement of 2 mL volume injected into the tumor;
6.For women of childbearing age (postmenopausal women must have been menopausal for at least 12 months to be considered infertile), the serum pregnancy test results are positive within 7 days before the intratumoral injection of the study drug; or the investigator judges that in the study During the period and within 3 months after the last administration of the study drug, those who are willing to become pregnant, breastfeeding, or unwilling to use effective contraceptive measures (including male subjects and their female spouses of childbearing age);
7.Within 4 weeks before the first administration of the study drug
(1)Have received chemotherapy, radiotherapy, biological/targeted drug therapy, immunological drug therapy and other anti-tumor treatments;
(2)Have received major surgery;
(3)Participated in other clinical trials and used or is using other experimental drug treatments (except for non-interventional drug clinical trials);
8.Other severe, acute, or chronic clinical or mental diseases or laboratory abnormalities that may increase the risk of research and research medication, or may interfere with the results of the research;
9.Patients with active autoimmune diseases or a history of autoimmune diseases but may relapse, but patients with the following diseases are not excluded and can be further screened: a. Type I diabetes b. Hypothyroidism (if only hormones are used Alternative therapies can be controlled) c. Controlled celiac disease d. Skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, hair loss) e. Any other diseases that will not recur without external triggers;
10.Active human immunodeficiency virus (HIV), syphilis, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection.
Active HBV, HCV and HIV infection are defined as:
(1)HBsAg positive and HBV DNA >= 1000 cps/mL (or 200 IU/mL);
(2)Anti-HCV antibody and HCV RNA positive;
(3)HIV antibody positive;
11.Those who are judged by the investigator to be intolerant of radiotherapy or have radiotherapy contraindications;
12.Cannot tolerate local injection of BM201 injection;
13.The investigator believes that the patient is not suitable to participate in this trial for any reason.

研究实施时间：

Study execute time：

从 From 2021-03-31 00:00:00至 To 2023-03-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2021-03-31 00:00:00 至 To 2023-03-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	7
Group：	experimental group	Sample size：	7
干预措施：	BM201&放疗	干预措施代码：
Intervention：	BM201&Radiotherapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江	市(区县)：	丽水
Country：	China	Province：	Zhejiang	City：	Lishui
单位(医院)：	丽水市中心医院	单位级别：	三级甲等
Institution hospital：	Lishui Central Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	不良反应	指标类型：	主要指标
Outcome：	Adverse effect	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	药代动力学指标	指标类型：	主要指标
Outcome：	Pharmacokinetic index	Type：	Primary indicator
测量时间点：		测量方法：	峰浓度（Cmax）、达峰时间（Tmax）、从用药前（0时）至用药后最终可测定时间t的血药浓度-时间曲线下面积（AUC0-t）、从用药前（0时）至用药后无限时间∞的血药浓度-时间曲线下面积（AUC0-∞）、半衰期（t1/2）、清除率（CL）和平均滞留时间（MRT）。
Measure time point of outcome：		Measure method：	Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, CL, MRT.

指标中文名：	客观缓解率	指标类型：	主要指标
Outcome：	Objective response 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：	主要指标
Outcome：	Progression free survival	Type：	Primary 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：	肿瘤组织	组织：
Sample Name：	Tumor	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）：

非随机对照

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

Non-randomized controlled trial.

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：	N/A
Blinding：	N/A
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	试验完成后6个月，丽水市中心医院
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	6 months after the completion of the experiment, Lishui Central Hospital
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：	丽水市中心医院
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Not stated
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：	2021-04-07 07:28:18