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：	ChiCTR2300069367
最近更新日期： Date of Last Refreshed on：	2023-05-24 18:21:19
注册时间： Date of Registration：	2023-03-14 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	在中国晚期实体瘤受试者中开展的 BC001 I 期临床研究
Public title：	Phase I clinical study of BC001 in Chinese subjects with advanced solid tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	在中国晚期实体瘤受试者中开展的 BC001 I 期临床研究
Scientific title：	Phase I clinical study of BC001 in Chinese subjects with advanced 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：	郭心磊	研究负责人：	沈琳
Applicant：	Guo Xinlei	Study leader：	Shen Lin
申请注册联系人电话： Applicant telephone：	+86 182 1079 6709	研究负责人电话： Study leader's telephone：	+86 10 8819 6391
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：	+86 10 88196391
申请注册联系人电子邮件： Applicant E-mail：	guoxinlei@buchangbio.com	研究负责人电子邮件： Study leader's E-mail：	doctorshenlin@sina.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：	北京市大兴区亦庄宏达北路8号宏达工业园八号科技广场8406室	研究负责人通讯地址：	北京海淀区阜成路52号
Applicant address：	Room 8406, Science and Technology Plaza, 8 Hongda Industrial Park, 8 Hongda Road North, Yizhuang, Daxing District, Beijing	Study leader's address：	52 Fucheng Road, Haidian District, Beijing, 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：	100142
申请人所在单位：	四川泸州步长生物制药有限公司
Applicant's institution：	Sichuan Luzhou Buchang Bio-Pharmaceutical Co., Ltd.
研究负责人所在单位：	北京大学肿瘤医院
Affiliation of the Leader：	Beijing University Cancer 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：	2018YW75	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：	北京肿瘤医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Beijing Cancer Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2018-08-27 00:00:00
伦理委员会联系人：	周顺连
Contact Name of the ethic committee：	Zhou Shunlian
伦理委员会联系地址：	北京海淀区阜成路52号
Contact Address of the ethic committee：	52 Fucheng Road, Haidian District, Beijing, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 10 8819 6391	伦理委员会联系人邮箱： Contact email of the ethic committee：	bzlunli@163.com

研究实施负责（组长）单位：

北京大学肿瘤医院

Primary sponsor：

Beijing University Cancer Hospital

研究实施负责（组长）单位地址：

北京海淀区阜成路52号

Primary sponsor's address：

52 Fucheng Road, Haidian District, Beijing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	四川省	市(区县)：	泸州市
Country：	China	Province：	Sichuan	City：	Luzhou
单位(医院)：	四川泸州步长生物制药有限公司	具体地址：	四川省泸州市泸县康乐大道西段480号
Institution hospital：	Sichuan Luzhou Buchang Bio-Pharmaceutical Co., Ltd.	Address：	480 West Section of Kangle Avenue, Lu County, Luzhou, Sichuan

经费或物资来源：

四川泸州步长生物制药有限公司

Source(s) of funding：

Sichuan Luzhou Buchang Bio-Pharmaceutical Co., Ltd.

研究疾病：

晚期实体瘤

Target disease：

Advanced solid 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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

递增阶段 1.主要目的：在晚期实体瘤受试者中，评估BC001单独和联合紫杉醇静脉输注给药的安全性和耐受性，确定最大耐受剂量（MTD）和/或扩展阶段推荐剂量（RDE），为后续临床试验给药方案和剂量提供依据。 2.次要目的： (1)在晚期实体瘤受试者中，研究BC001静脉输注给药的药代动力学（PK）特征。 (2)依据RECIST 1.1版，初步评估BC001单独和联合紫杉醇在晚期实体瘤的疗效。研究扩展阶段 1.主要目的：依据RECIST 1.1版，初步评估BC001单独和与化疗或免疫治疗联用在方案规定瘤种受试者中的疗效。 2.次要目的：评估BC001单独和联合化疗或免疫治疗的安全性。

Objectives of Study：

Dose escalation phase 1.Primary Objectives: In subjects with advanced solid tumors, evaluate the safety and tolerance of BC001 alone and in combination with intravenous infusion of paclitaxel, and determine the maximum tolerated dose (MTD) and/or the recommended dose for research expansion phase (RDE), so as to provide basis for the administration scheme and dose of subsequent clinical trials. 2.Secondary Objectives: (1) The pharmacokinetic (PK) characteristics of BC001 intravenous infusion were studied in subjects with advanced solid tumors. (2) According to RECIST version 1.1, the efficacy of BC001 alone and combined with paclitaxel in advanced solid tumors was preliminarily evaluated. Research expansion phase 1.Primary Objectives: According to RECIST version 1.1, the efficacy of BC001 alone and in combination with chemotherapy or immunotherapy in patients with tumor species specified in the protocol was preliminarily evaluated. 2.Secondary Objectives: To evaluate the safety of BC001 alone and in combination with chemotherapy or immunotherapy.

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. Subjects must be able to understand and voluntarily sign written informed consent. Informed consent includes dose escalation, research expansion phase, and relevant requirements for sample collection in the two-phase study;
2. Subjects must be voluntary and able to complete the research procedures and follow-up examinations;
3. Male or female subjects aged >= 18 years;
4. Dose escalation phase: subjects with advanced malignant solid tumors confirmed by histopathology or cytopathology, mainly including but not limited to: gastric cancer and gastroesophageal junction adenocarcinoma, non-small cell lung cancer, metastatic colorectal cancer, Melanoma, renal cell carcinoma, bladder urothelial carcinoma, osteosarcoma, neuroendocrine tumor, etc.;
Research expansion Phase: Subjects with advanced malignant solid tumors confirmed by histopathology or cytopathology, including but not limited to: gastric cancer and gastroesophageal junction adenocarcinoma, non-small cell lung cancer, metastatic colorectal cancer, melanoma Tumor, renal cell carcinoma, bladder urothelial carcinoma, osteosarcoma, neuroendocrine tumor, etc., according to RECIST version 1.1 to determine at least one measurable tumor lesion shown by CT or MRI;
*Measurable lesions are defined as >= 10 mm in longest diameter and no more than 5.0 mm in scan thickness. For lymph node lesions, the short diameter is >= 15 mm;
5. In research expansion phase, subjects who have progressed after first-line standard treatment, can not tolerate standard treatment or have no standard treatment are enrolled;
6. The ECOG score is 0-1;
7. The estimated life expectancy >= 3 months;
8. No serious hematology, liver and kidney function abnormalities, in line with the following laboratory test results:
(1) Hematology: neutrophils >= 1.5 x 10^9/L, platelets >= 75 x 10^9/L, hemoglobin >= 90 g/L;
(2) Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= upper limit of normal x 3.0; alkaline phosphatase (ALP) <= upper limit of normal x 2.5; total bilirubin (TBIL) <= upper limit of normal x 1.5;
(3) Renal function: creatinine clearance rate calculated according to the Cockcroft-Gault formula >= 50 mL/min;
(4) Coagulation function: International normalized ratio (INR) <= 1.5 or prothrombin time (PT) <= 1.5 x ULN or activated partial prothrombin time (APTT) <= 1.5 x ULN. Subjects receiving anticoagulant therapy should receive stable doses of oral anticoagulants or low molecular weight heparin. If the subject treated with warfarin, the INR should be <= 3.0 without active bleeding (no bleeding within 14 days prior to the study drug) or clinical conditions with an increased risk of bleeding; 
(5) Urine routine test urine protein concentration <= 1+, without edema or serum albumin level lower than LLN;
9. Recovery from adverse events of prior anti-tumor therapy to baseline or <= grade 1 (except: alopecia and vitiligo; prior anti-tumor therapy-induced neuropathy stable or <= grade 2);
10. Male or female subjects take effective contraceptive measures during treatment and within 6 months after the last dose.

排除标准：

1.入组前4周内接受过抗肿瘤治疗或临床试验，包括系统化疗、放疗或免疫治疗。入组前4周内接受过贝伐单抗或其他VEGF/VEGFR抗体治疗； 2.研究扩展阶段：入组PD1治疗组的受试者，既往接受过抗PD-1、抗PD-L1、抗PD-L2、抗CTLA-4抗体或其他T细胞协同刺激/检查点通路的抗体治疗； 3.患有本研究所治疗肿瘤以外的其他恶性肿瘤疾病（例外情况包括：治愈且在研究入选前3年内没有复发的恶性肿瘤；完全切除的基底细胞和鳞状细胞皮肤癌；完全切除的任何类型的原位癌）； 4.原有病灶侵及中枢神经系统（CNS）并有症状，不稳定或需要高剂量类固醇（≥10mg地塞米松或等效剂量）以达到控制； 5.需要全身性治疗的活动性感染（如病毒、细菌或真菌感染）； 6.近4周内有活动性出血病史或有胃肠道穿孔危险、近期手术尚未愈合或手术操作导致创口并发症病史的受试者； 7.研究治疗首次给药前4周内接受过大手术； 8.研究用药前2周内接受过集落刺激因子、促红细胞生成素等治疗； 9.研究用药前4周内接种过活疫苗； 10.受试者存在未控制的间发性疾病，包括但不限于：血栓形成或出血性疾病、咯血、持续或活动性感染需要系统性抗生素治疗、充血性心力衰竭（纽约心脏病协会III或IV级心脏病）；研究用药前6个月内出现心绞痛、接受血管成形术、支架术或出现心肌梗塞；研究用药前6个月内出现卒中、短暂性脑缺血发作（TIA）或其他≥3级动脉血栓栓塞事件；不受控制的高血压（标准治疗后血压≥150/90 mmHg）；需要治疗的心律失常（CTCAE v5.0≥3级）或无症状、持续性室性心动过速；任何病因的≥2级（CTCAE v5.0）周围神经病； 11.受试者在研究用药前3个月内发生过≥3级（CTCAE v5.0）胃肠道出血；在研究用药前2周内存在严重胃肠道疾病； 12.正在接受非甾体类抗炎药（如吲哚美辛、布洛芬等）或抗血小板药物（如氯吡格雷、噻氯匹定、双嘧达莫等）长期治疗（允许使用阿司匹林，每日最大剂量325mg）； 13.乙肝表面抗原阳性，且HBV DNA拷贝数>检测单位正常值；丙型肝炎病毒抗体阳性且HCV RNA阳性者； 14.人类免疫缺陷病毒感染史，或患有其它获得性、先天免疫缺陷疾病，或有器官移植史者； 15.已知对研究药物、单抗及其他治疗性蛋白制剂（新鲜或冰冻血浆、人血清白蛋白、细胞因子、白介素等）过敏； 16.已知有酒精和/或药物依赖者； 17.血妊娠试验阳性或在哺乳期女性受试者； 18.研究者判断其他原因导致不适合参加本研究的受试者。

Exclusion criteria：

1. Received anti-tumor therapy or clinical trials within 4 weeks before enrollment, including systemic chemotherapy, radiotherapy or immunotherapy. Received bevacizumab or other VEGF/VEGFR antibody therapy within 4 weeks before enrollment; 2. Research expansion phase: the subjects in the PD1 treatment group have previously received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies or other antibodies for T cell co stimulation / checkpoint pathway; 3. Suffering from other malignancies other than the tumors treated in this study (exceptions include: malignancies that are cured and have not recurred within 3 years prior to study enrollment; completely resected basal cell and squamous cell skin cancers; completely resected any type of carcinoma in situ); 4. The original lesion invades the central nervous system (CNS) and is symptomatic, unstable or requires high-dose steroids (>= 10 mg dexamethasone or equivalent dose) to achieve control; 5. Active infections (such as viral, bacterial or fungal infections) requiring systemic treatment; 6. Subjects with a history of active bleeding within the past 4 weeks or a risk of gastrointestinal perforation, recent surgery that has not healed, or a history of wound complications caused by surgical operations; 7. Major surgery within 4 weeks before the first dose of study treatment; 8. Received colony-stimulating factor, erythropoietin and other treatments within 2 weeks before the study drug; 9. Received with live vaccine within 4 weeks before study medication; 10. Subject has uncontrolled episodic disease, including but not limited to: thrombotic or bleeding disorders, hemoptysis, persistent or active infection requiring systemic antibiotic therapy, congestive heart failure (New York Heart Association III or Grade IV heart disease); angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months prior to study medication; stroke, transient ischemic attack (TIA) or other ≥ 6 months prior to study medication Grade 3 arterial thromboembolic event; uncontrolled hypertension (BP >= 150/90 mmHg after standard therapy); arrhythmia requiring treatment (CTCAE v5.0 >= Grade 3) or asymptomatic, sustained ventricular tachycardia; Grade >= 2 (CTCAE v5.0) peripheral neuropathy of any etiology; 11. The subject has experienced >= grade 3 (CTCAE v5.0) gastrointestinal bleeding within 3 months before the study medication; severe gastrointestinal disease within 2 weeks before the study medication; 12. Receiving long-term treatment with non steroidal anti-inflammatory drugs (such as indomethacin, ibuprofen, etc.) or antiplatelet drugs (such as clopidogrel, ticlopidine, dipyridamole, etc.) (aspirin is allowed, with a maximum daily dose of 325mg); 13. Hepatitis B surface antigen positive, and HBV DNA copy number > the normal value of the detection unit; Hepatitis C virus antibody positive and HCV RNA positive; 14. History of human immunodeficiency virus infection, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 15. Known allergy to study drugs, monoclonal antibodies and other therapeutic protein preparations (fresh or frozen plasma, human serum albumin, cytokines, interleukins, etc.); 16. Known to be alcohol and/or drug dependent; 17. Positive blood pregnancy test or female subjects who are breastfeeding; 18. Subjects who are judged by the investigator to be unsuitable to participate in this study due to other reasons.

研究实施时间：

Study execute time：

从 From 2019-02-21 00:00:00至 To 2023-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2019-02-21 00:00:00 至 To 2023-12-31 00:00:00

干预措施：

Interventions：

组别：	剂量递增	样本量：	15
Group：	dose escalation	Sample size：	15
干预措施：	BC001	干预措施代码：
Intervention：	BC001	Intervention code：

组别：	剂量递增	样本量：	13
Group：	dose escalation	Sample size：	13
干预措施：	BC001+紫杉醇	干预措施代码：
Intervention：	BC001+paclitaxel	Intervention code：

组别：	剂量扩展	样本量：	4
Group：	dose expansion	Sample size：	4
干预措施：	BC001	干预措施代码：
Intervention：	BC001	Intervention code：

组别：	剂量扩展	样本量：	21
Group：	dose expansion	Sample size：	21
干预措施：	BC001+紫杉醇	干预措施代码：
Intervention：	BC001+paclitaxel	Intervention code：

组别：	剂量扩展	样本量：	90
Group：	dose expansion	Sample size：	90
干预措施：	BC001+化疗	干预措施代码：
Intervention：	BC001+chemotherapy	Intervention code：

组别：	剂量扩展	样本量：	90
Group：	dose expansion	Sample size：	90
干预措施：	BC001+PD-1/PD-L1	干预措施代码：
Intervention：	BC001+PD-1/PD-L1	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	北京大学肿瘤医院	单位级别：	三级甲等
Institution hospital：	Beijing University Cancer Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	黑龙江	市(区县)：	哈尔滨
Country：	China	Province：	Heilongjiang	City：	Harbin
单位(医院)：	哈尔滨医科大学附属肿瘤医院	单位级别：	三级甲等
Institution hospital：	Cancer Hospital affiliated to Harbin Medical University	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	安徽	市(区县)：	蚌埠
Country：	China	Province：	Anhui	City：	Bengbu
单位(医院)：	蚌埠医学院第一附属医院	单位级别：	三级甲等
Institution hospital：	The First Affiliated Hospital of Bengbu Medical College	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	河北	市(区县)：	沧州
Country：	China	Province：	Hebei	City：	Cangzhou
单位(医院)：	沧州市人民医院	单位级别：	三级甲等
Institution hospital：	Cangzhou People's Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	在晚期实体瘤受试者中，BC001每个剂量水平DLT及发生率（剂量递增阶段）	指标类型：	主要指标
Outcome：	DLT and incidence of BC001 per dose level in subjects with advanced solid tumors (Dose escalation phase)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	在晚期实体瘤受试者中，与紫杉醇联合使用的BC001每个剂量水平DLT及发生率（剂量递增阶段）	指标类型：	主要指标
Outcome：	DLT and incidence of BC001 per dose level used in combination with paclitaxel in subjects with advanced solid tumors (Dose escalation phase)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	通过安全性指标：治疗后不良事件、血常规、血生化和尿常规等实验室检查结果、体格检查、生命体征和心电图评估BC001在中国晚期实体瘤受试者中的安全性（剂量递增阶段）	指标类型：	主要指标
Outcome：	The safety of BC001 in Chinese subjects with advanced solid tumors was assessed by post-treatment adverse events, blood routine, blood chemistry and urine routine laboratory tests, physical examination, vital signs, and electrocardiogram (Dose-escalation phase)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	在晚期实体瘤受试者中，BC001药代动力学参数（剂量递增阶段）	指标类型：	次要指标
Outcome：	In subjects with advanced solid tumors, BC001 pharmacokinetic parameters (Dose-escalation phase)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	在实体瘤受试者中，初步评估BC001单药及BC001与紫杉醇联用的有效性，包括：客观总体缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DOR）和无进展生存时（PFS）（剂量递增阶段）	指标类型：	次要指标
Outcome：	In subjects with solid tumours, the effectiveness of BC001 monotherapy and BC001 combined with paclitaxel was initially evaluated, including: objective overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) (Dose-escalation phase)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	在方案规定瘤种的受试者中，初步评估BC001单独和与化疗或免疫治疗联用的有效性，包括：客观总体缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DOR）和无进展生存时间（PFS）（研究扩展阶段）	指标类型：	主要指标
Outcome：	Determine the efficacy of BC001 alone and in combination with chemotherapy or immunotherapy, including: objective overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival time (PFS) (Study Extension Phase)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	通过安全性指标，即治疗后不良事件、血常规、血生化和尿常规等实验室检查结果、体格检查、生命体征和心电图，分别评估BC001单独和联合化疗或免疫治疗在方案规定瘤种的受试者中的安全性（研究扩展阶段）	指标类型：	次要指标
Outcome：	The safety of BC001 alone and in combination with chemotherapy or immunotherapy in subjects with protocol specified tumors was evaluated by safety measures, including post-treatment adverse events, blood routine, blood chemistry and urine tests, physical examination, vital signs, and electrocardiogram (Study Extension Phase)	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：	尿液	组织：
Sample Name：	urine	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：

结束

/Completed

年龄范围：

Participant age：

最小 Min age		岁 years
最大 Max age		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）：

不适用

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

NA

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：
Blinding：

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）：	https://study.cims-medtech.com/C020/?uc=C020
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	https://study.cims-medtech.com/C020/?uc=C020
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：	电子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Electronic Data Capture, EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2023-03-14 17:25:29