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：	ChiCTR2300073093
最近更新日期： Date of Last Refreshed on：	2023-08-27 21:00:58
注册时间： Date of Registration：	2023-06-30 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项探索CD-801治疗中晚期肝癌患者安全性及有效性的临床试验
Public title：	A clinical trial for the safety and efficacy of CD-801 in patients with advanced hepatocellular carcinoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项探索CD-801治疗中晚期肝癌患者安全性及有效性的临床试验
Scientific title：	A clinical trial for the safety and efficacy of CD-801 in patients with advanced hepatocellular carcinoma
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：	尹川	研究负责人：	谢渭芬
Applicant：	Yin Chuan	Study leader：	Xie Weifen
申请注册联系人电话： Applicant telephone：	+86 134 8270 5212	研究负责人电话： Study leader's telephone：	+86 137 0168 2806
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：	ilse1225@163.com	研究负责人电子邮件： Study leader's E-mail：	weifenxie@medmail.com.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：	上海市黄浦区凤阳路415号	研究负责人通讯地址：	上海是黄浦区凤阳路415号
Applicant address：	415 Fengyang Road, Huangpu District, Shanghai	Study leader's address：	415 Fengyang Road, Huangpu District, Shanghai
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：	上海长征医院
Applicant's institution：	Shanghai Changzheng Hospital
研究负责人所在单位：	上海长征医院
Affiliation of the Leader：	Shanghai Changzheng 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：	2023SL036	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：	上海长征医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Shanghai Changzheng Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2023-06-27 00:00:00
伦理委员会联系人：	孙吕平
Contact Name of the ethic committee：	Sun Lyuping
伦理委员会联系地址：	上海市黄浦区凤阳路415号
Contact Address of the ethic committee：	415 Fengyang Road, Huangpu District, Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 8188 5046	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：

上海长征医院

Primary sponsor：

Shanghai Changzheng Hospital

研究实施负责（组长）单位地址：

上海市黄浦区凤阳路415号

Primary sponsor's address：

415 Fengyang Road, Huangpu District, Shanghai

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(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海长征医院	具体地址：	上海市黄浦区凤阳路415号
Institution hospital：	Shanghai Changzheng Hospital	Address：	415 Fengyang Road, Huangpu District, Shanghai

经费或物资来源：

上海长征医院

Source(s) of funding：

Shanghai Changzheng Hospital

研究疾病：

中晚期肝癌

Target disease：

Advanced hepatocellular 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：

探索性研究/预试验

Study phase：

0

研究设计：

连续入组

Study design：

Sequential

研究目的：

评价CD-801注射液在中晚期肝癌受试者中的安全性及有效性。

Objectives of Study：

To evaluate the safety and efficacy of CD-801 in patients with advanced hepatocellular carcinoma.

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. Males or females, aged 18 years or older;
2. Subjects must have confirmed diagnosis of HCC with any of the following criteria according to the American Association for the Study of Liver Diseases criteria:
(1) In those most at-risk patients with HBV/HCV infection or cirrhosis from any etiology, the diagnosis of HCC in lesions >= 1 cm in size could be based on noninvasive imaging criteria: arterial phase hyperenhancement (APHE) and washout on portal venous or delayed phases of contrast-enhanced multiphase CT or MRI;
(2) Histologically or cytologically confirmed diagnosis of HCC;
3. Unresectable HCC;
4. Subjects are not eligible for locoregional or systemic therapies, or had disease progression or would not benefit after at least one of the therapies according to any of the following criteria:
(1) CT/MRI examination showed residual tumors 1 month after 2 or more ablation treatments;
(2) After 2 or more TACE treatments, CT/MRI examination showed more than 50% definite viable disease, development of new HCC, new vascular invasion or extrahepatic metastases, or improvement for tumor markers lacked;
(3) According to mRECIST, subjects had disease progression while receiving at least one systemic therapy, or were intolerant of systemic therapies;
5. According to mRECIST, subjects should be with at least 1 measurable target lesion meeting the following criteria:
(1) The lesion could be accurately measured in at least 1 dimension as 1 cm or more;
(2) The lesion is suitable for repeat measurement;
(3) The lesion shows intratumoral arterial enhancement on contrast-enhanced MRI;
(4) The longest diameter of the lesion for intratumoral injection should be 5.0 cm or less;
Lesions previously treated with surgical resection, radiotherapy or locoregional therapy must show radiographic evidence of disease progression according to mRECIST to be deemed a target lesion;
6. Life expectancy of 12 weeks or more;
7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2;
8. Male with fertility and females of childbearing potential are willing to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation. Females of childbearing age, including premenopausal females and within 2 years after menopause, must have a negative serum pregnancy test result within 7 days prior to the first dose of study treatment;
9. Subjects who have voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

排除标准：

1.白蛋白 < 28 g/L，或胆红素 > 5.0 mg/dL，或天冬氨酸转氨酶、碱性磷酸酶或丙氨酸转氨酶 > 5×ULN； 2.明显肾功能不全者，血清肌酐 > 1. 5×ULN，或肌酐清除率 < 40 mL/min； 3.中性粒细胞绝对计数 < 1.0×109/L ，或血小板 < 30×109/L，或血红蛋白 < 8.5 g/dL； 4.国际标准化比率（International Normalized Ratio，INR） > 2.3； 5.曾行肝脏移植手术； 6.合并控制不佳的高血压、糖尿病或其他严重心、肺疾病者，或者严重的功能障碍者； 7.明确有肝外转移的患者，未接受过一线系统治疗（不适合系统抗肿瘤治疗患者除外）或目前系统治疗有效者； 8.4周内接受过消融、TACE等局部或免疫、靶向及化疗等系统（如口服索拉非尼为2周内）抗肿瘤治疗、或3周内接受过放疗、或2周内接受过槐耳颗粒等传统中药的抗肿瘤治疗，根据mRECIST标准疗效评估为疾病进展的治疗方案除外； 9.目前与既往局部或系统抗肿瘤治疗相关的不良反应仍 ≥2级（除脱发和其他经研究者判断可耐受的事件除外）； 10.2周内存在消化道出血、显性肝性脑病、难控制的腹水等肝硬化或肝癌并发症； 11.难以控制的现症感染者（如肺部感染、腹腔感染等）； 12.数字减影血管造影显示中重度的肝动脉-门静脉瘘或肝动脉-肝静脉瘘，且瘘口通过超选动脉也无法避开，瘤内注射受试者除外； 13.5年内患有除HCC以外的恶性肿瘤，转移或死亡风险较低（预计5年总体生存率> 90%的肿瘤）的恶性肿瘤除外，如有效治疗后的胃肠道早癌、宫颈原位癌、非黑色素瘤皮肤癌、局限性前列腺癌等； 14.HBV-DNA＞500 IU/mL者；或HCV RNA＞100 IU/mL者； 15.人类免疫缺陷病毒（HIV）阳性； 16.MRI造影剂过敏； 17.妊娠/哺乳期妇女，或不能排除妊娠可能的妇女； 18.4周内参加过其他药物试验者； 19.研究者认为不适合参与本临床试验的其他情况。

Exclusion criteria：

1. ALB < 28 g/L, or Bilirubin > 5.0 mg/dL, or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) > 5×ULN; 2. Inadequate renal function defined as creatinine >1.5 times the upper limit of normal (ULN) or calculated creatinine clearance < 40 mL/min; 3. Absolute neutrophil count (ANC) < 1.0×10^9/L, or Platelets < 30×10^9/L, or Hemoglobin < 8.5 g/dL; 4. International Normalized Ratio (INR) > 2.3; 5. Subjects with a history of liver transplantation; 6. Subjects with poorly controlled hypertension, diabetes or other serious heart or lung diseases, or with serious dysfunction; 7. Subjects with extrahepatic metastasis who have not received first-line systemic therapies (excluding those who are not eligible for systemic therapies) or who are receiving effective systemic therapy currently; 8. Subjects who had prior anticancer treatment with any locoregional therapies, antiangiogenic targeted therapies, immune checkpoint inhibitors or chemotherapy (within 4 weeks, or within 2 weeks in case of sorafenib), radiotherapy (within 3 weeks), or active traditional Chinese medicine (within 2 weeks) before the first dose of study treatment, except for the treatments after which the disease still progressed according to mRECIST; 9. All toxicities related to prior locoregional or systemic anti-tumor treatments are still grade 2 or more (except for hair loss and other events that have been judged tolerable by researchers); 10. Subjects with complication histories of liver cirrhosis or HCC such as gastrointestinal hemorrhage, overt hepatic encephalopathy, or uncontrollable ascites within 2 weeks prior to the first dose of study treatment; 11. Uncontrolled active infection (eg, lung infections, or abdominal infections); 12. Subjects with moderate to severe hepatic artery- portal vein fistula or hepatic artery - vein fistula which could not be avoided even through the artery super selection by DSA, excluding subjects who will receive intratumoral injection; 13. History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated early gastric carcinoma, carcinoma in situ of the cervix, non-melanoma skin carcinoma, or localized prostate cancer; 14. HBV DNA greater than 500 IU/mL, or HCV RNA greater than 100 IU/mL; 15. Subject is positive for Human Immunodeficiency Virus (HIV); 16. Any subject who is allergic to MRI contrast agents; 17. Pregnant/lactating women, or women who have the possibility of pregnancy; 18. Participation in other investigational drug trials within 4 weeks prior to initiation of this study treatment; 19. Any medical or other condition which, in the opinion of the investigator, would preclude participation in this clinical trial.

研究实施时间：

Study execute time：

从 From 2023-07-01 00:00:00至 To 2024-06-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-07-01 00:00:00 至 To 2024-06-30 00:00:00

干预措施：

Interventions：

组别：	治疗组	样本量：	29
Group：	Treated group	Sample size：	29
干预措施：	经肝动脉注射和/或瘤内注射CD-801	干预措施代码：
Intervention：	Treated by CD-801 through the hepatic artery and/or intratumoral injection	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)：	上海长征医院	单位级别：	三级甲等
Institution hospital：	Shanghai Changzheng Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	中国人民解放军总医院	单位级别：	三级甲等
Institution hospital：	Chinese PLA General Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	剂量递增阶段评估CD-801治疗的限制性毒性和最大耐受剂量	指标类型：	主要指标
Outcome：	To evaluate the dose limiting toxicities and maximum tolerated dose for the treantment of CD-801 in the 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：	剂量扩展阶段根据mRECIST和RECIST v1.1标准评价治疗后客观缓解率	指标类型：	主要指标
Outcome：	To assess the objective response rate (ORR) by mRECIST and RECIST v1.1 in the dose-expansion 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：	剂量递增阶段根据mRECIST和RECIST v1.1标准评价的ORR	指标类型：	次要指标
Outcome：	To evaluate objective response rate (ORR) by mRECIST and RECIST v1.1 in the 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：	剂量扩展阶段通过应答持续时间、无进展生存期、进展时间、治疗起效时间、疾病控制率、临床获益率以及受试者总生存期等评估CD-801治疗肝癌的有效性	指标类型：	次要指标
Outcome：	To evaluate duration of response, progression-free survival,time to progression,time to response,disease control rate,and clinical benefit rate by mRECIST and RECIST v1.1 in the dose-expansion 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：	剂量扩展阶段通过受试者生活质量评估CD-801治疗肝癌的有效性，并探索血液或组织中生物标志物变化情况	指标类型：	附加指标
Outcome：	To evaluate the impact of CD-801 treatment on Health Related Quality of Life and to investigate the changes of biomarkers in serum or HCC tissues after treatment.	Type：	Additional 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：	经皮肝穿刺获取肝癌组织	组织：
Sample Name：	HCC tissue obtained through biopsy	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	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）：

无

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

None

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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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：	EDC
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：	2023-06-30 17:25:50