ChiCTR2300075966 版本V1.0 版本创建时间2023/09/20 16:17:40 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2300075966 

最近更新日期：

Date of Last Refreshed on：

 2023-09-20 16:17:19 

注册时间：

Date of Registration：

 2023-09-20 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

HR070803联合5-FU/LV与BP102二线治疗转移性结直肠癌

Public title：

Second-line treatment of metastatic colorectal cancer with HR070803 in combination with 5-FU/LV and BP102

注册题目简写：

English Acronym：

研究课题的正式科学名称：

HR070803（伊立替康脂质体）联合5-FU/LV与BP102（贝伐珠单抗）二线治疗转移性结直肠癌：一项开放标签、单中心、单臂研究

Scientific title：

Second-line treatment of metastatic colorectal cancer with HR070803 (irinotecan liposome) in combination with 5-FU/LV and BP102 (bevacizumab): an open-label, single-center, single-arm study

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：

陈治宇 

研究负责人：

陈治宇 

Applicant：

Zhiyu Chen 

Study leader：

Zhiyu Chen 

申请注册联系人电话：

Applicant telephone：

 +86 187 2184 1159

研究负责人电话：

Study leader's
telephone：

+86 187 2184 1159

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：

 chanhj75@aliyun.com

研究负责人电子邮件：

Study leader's E-mail：

 chanhj75@aliyun.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：

上海市东安路270号

研究负责人通讯地址：

上海市东安路270号

Applicant address：

No.255, Dong’An Road, Shanghai

Study leader's address：

No.255, Dong’An Road, 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：

复旦大学附属肿瘤医院

Applicant's institution：

Fudan University Shanghai Cancer Center

研究负责人所在单位：

复旦大学附属肿瘤医院

Affiliation of the Leader：

Fudan University Shanghai Cancer Center

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：

 2307279-12

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：

复旦大学附属肿瘤医院医学伦理委员会

Name of the ethic committee：

Ethics Committee of Fudan University Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-08-16 00:00:00

伦理委员会联系人：

张玮静

Contact Name of the ethic committee：

Weijing Zhang

伦理委员会联系地址：

上海市东安路270号

Contact Address of the ethic committee：

No.255, Dong’An Road, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 21 3477 8299

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：

复旦大学附属肿瘤医院

Primary sponsor：

Fudan University Shanghai Cancer Center

研究实施负责（组长）单位地址：

上海市东安路270号

Primary sponsor's address：

No.255, Dong’An Road, 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)：

复旦大学附属肿瘤医院

具体地址：

上海市东安路270号

Institution
hospital：

Fudan University Shanghai Cancer Center

Address：

No.255, Dong’An Road, Shanghai

经费或物资来源：

基金

Source(s) of funding：

funding

研究疾病：

结直肠癌  

Target disease：

colorectal cancer

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：

评估HR070803联合5-FU/LV与BP102用于结直肠癌2线治疗的有效性和安全性  

Objectives of Study：

Evaluating the efficacy and safety of HR070803 in combination with 5-FU/LV and BP102 for 2nd line treatment of colorectal cancer

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1. 18-75岁，性别不限； 2. 经病理学确诊的晚期结、直肠腺癌（所有其他组织学类型都排除在外）患者； 3. 既往曾接受过一线标准治疗且治疗失败或辅助治疗期间或完成后 ≤6 个月内出现疾病进展； “治疗失败”的定义：（1）治疗过程中疾病进展或末次治疗后的3个月内疾病进展，均有明确影像学或临床进展证据；（2）因无法耐受治疗不良事件而退出一线治疗的患者，按 CTCAE 5.0标准，其不耐受的血液学不良事件严重等级达到 IV 级以上（血小板下降为III级以上）或非血液学不良事件严重等级达到 III 级以上，且研究者判断该受试者重复原方案治疗仍然无法耐受。 4. 根据 RECIST 1.1 标准，患者至少具有一个可测量的靶病灶； 5. ECOG评分：0~1 分（详见附件二）； 6. 预计生存期 ≥3 个月； 7. 主要器官功能良好，即随机前14天内相关检查指标满足以下要求： （1）血常规检查（筛选前14天内未输血，未用过升白、升血小板药物）：血红蛋白 > 90 g/L；中性粒细胞计数> 1.5×109/L；血小板计数> 100×109/L； （2）生化检查：总胆红素 ≤ 1.5×ULN（正常值上限）；血谷丙转氨酶（ALT）和血谷草转氨酶（AST）≤ 2×ULN；如有肝转移，则ALT和AST ≤ 5×ULN；内生肌酐清除率 ≥ 60 ml/min（Cockcroft-Gault公式）；（3）心脏多普勒超声评估：左室射血分数 (LVEF，Left ventricular ejection fraction) ≥ 50%。 8. 受试者接受其它治疗造成的损害已恢复； 9. 受试者自愿加入本研究，签署知情同意书，依从性好，配合随访。

Inclusion criteria

1. 18-75 years of age and either sex; 2. Patients with pathologically confirmed advanced colorectal and rectal adenocarcinoma (all other histologic types excluded); 3. Previous failure of standard first-line therapy or disease progression during or ≤6 months after completion of adjuvant therapy; "Treatment failure" is defined as (1) disease progression during treatment or within 3 months of the last dose of treatment, with clear evidence of imaging or clinical progression, and (2) withdrawal from first-line treatment due to intolerance of an adverse event with an intolerable severity grade of an adverse hematologic event of grade IV or higher (platelet count decreased ≥1%), as defined by CTCAE 5.0 criteria. Grade IV or higher (platelet count decreased is Grade III or higher) or a non-hematologic adverse event severity grade of Grade III or higher, and in the judgment of the investigator, the subject would still be unable to tolerate treatment by repeating the original regimen. 4. The patient has at least one measurable target lesion according to RECIST 1.1 criteria; 5. ECOG score: 0~1 (see Annex II for details); 6. Expected survival ≥3 months; 7. Good function of major organs, i.e., relevant examination indexes meet the following requirements within 14 days before enrollment: (1) Routine blood tests (no blood transfusion within 14 days before screening, no drugs for raising white blood or platelets): hemoglobin > 90 g/L; neutrophil count > 1.5×109/L; platelet count > 100×109/L; (2) Biochemical tests: total bilirubin ≤ 1.5×ULN (upper limit of normal); blood alanine aminotransferase (ALT) and blood azelaic transaminase (AST) ≤ 2×ULN; if liver metastases are present, ALT and AST ≤ 5×ULN; endogenous creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula); (3) cardiac Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF, Left ventricular ejection fraction) ≥ 50%. 8. The subject has recovered from the damage caused by other treatments; 9. Subjects voluntarily enrolled in the study, signed the informed consent form, had good compliance, and cooperated with the follow-up visits.

排除标准：

1. 以往或同时患有其它恶性肿瘤，但是已治愈的皮肤基底细胞癌和宫颈原位癌除外； 2. 既往接受过伊立替康治疗的患者； 3. 肿瘤组织经免疫组化方法证实为dMMR状态，或二代测序（NGS）/聚合酶链式反应（PCR）方法确认为MSI-H状态; 4. 二代测序（NGS）/聚合酶链式反应（PCR）方法确认为BRAF V600E突变； 5. 入组前四周内参加过其他药物临床试验； 6. 筛选期存在明显的胃肠道异常，经研究者判断可能会影响药物的摄入、转运或吸收（如无法吞咽、慢性腹泻、肠梗阻、小肠切除术后或全胃切除等）；或既往有消化道穿孔和/或瘘管病史；首次用药前6个月内有消化性溃疡病史；首次用药前3个月内发生过肠梗阻； 7. 有出血病史，筛选前4周内发生任何严重分级达到 CTCAE 5.0 3 级或以上的出血事件； 8. 筛选前已知有中枢神经系统转移或有中枢神经系统转移病史的患者。对于临床疑似中枢神经系统转移的患者，随机化前28天内必须进行增强CT或增强核磁共振（MRI）检查，排除中枢神经系统转移； 9. 患有高血压且经单一降压药物治疗无法获得良好控制者（收缩压 > 140 mmHg，舒张压 > 90 mmHg）；具有不稳定型心绞痛病史者；筛选前3个月内新诊断为心绞痛者或筛选前6个月内发生心肌梗塞事件；心律失常（包括QTcF：男性≥450 ms，女性≥470 ms）需长期使用抗心律失常药物及纽约心脏病协会分级≥II级心功能不全； 10. 尿常规提示尿蛋白≥++且证实24小时尿蛋白定量>1.0 g； 11. 长期未愈合的伤口或愈合不全的骨折； 12. 影像学显示肿瘤已侵犯重要血管周围或经研究者判断患者肿瘤在治疗期间有极高可能侵袭重要血管而引起致命大出血的情况； 13. 凝血功能异常，具有出血倾向者（入组前14天必须满足：在不使用抗凝剂的情况下INR在正常值范围内）；应用抗凝剂或维生素K 拮抗剂如华法林、肝素或其类似物治疗的患者；在凝血酶原时间国际标准化比值（INR，International Normalized Ratio）≤ 1.5的前提下，允许以预防目的使用小剂量华法林（1 mg口服，每日一次）或小剂量阿司匹林（每日用量不超过100 mg）； 14. 筛选前一年内发生过动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作）、深静脉血栓（因前期化疗行静脉置管引发静脉血栓经研究者判断已痊愈者除外）及肺栓塞等； 15. 对于女性受试者：非手术绝育或非绝经后的患者拒绝在研究治疗期间和研究治疗期结束后6个月内采用一种经医学认可的避孕措施；育龄女性在研究入组前的7天内血清或尿妊娠试验为阳性，或正处于哺乳期。男性受试者：非手术绝育且拒绝在研究治疗期间和研究治疗期结束后6个月内采用一种经医学认可的避孕措施的患者； 16. 根据研究者的判断，有严重的危害患者安全或影响患者完成研究的伴随疾病； 17. 研究者判断其他可能影响临床研究进行及研究结果判定的情况。

Exclusion criteria：

1. Previous or concurrent other malignancies, except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix; 2. Patients who have received prior irinotecan therapy; 3. Tumor tissue with dMMR status confirmed by immunohistochemistry or MSI-H status by second-generation sequencing (NGS)/polymerase chain reaction (PCR). 4. BRAF V600E mutation confirmed by second-generation sequencing (NGS)/polymerase chain reaction (PCR); 5. Participation in a clinical trial of another drug within four weeks before enrollment; 6. presence of significant gastrointestinal abnormalities during the screening period that, in the judgment of the investigator, may interfere with the ingestion, transit, or absorption of the drug (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, post-small bowel resection or total gastrectomy, etc.); or previous history of gastrointestinal perforation and/or fistulae; a history of peptic ulcer within 6 months before the first administration of the drug; and intestinal obstruction within 3 months before the first administration of the drug; 7. History of bleeding, any bleeding event with a severity rating of CTCAE 5.0 Grade 3 or higher within 4 weeks before screening; 8. Patients with known CNS metastases or a history of CNS metastases before screening. For patients with clinically suspected CNS metastases, an enhanced CT or enhanced magnetic resonance imaging (MRI) must be performed within 28 days before enrollment to rule out CNS metastases; 9. patients with hypertension that is not well controlled with a single antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); those with a history of unstable angina; those with a new diagnosis of angina pectoris in the 3 months before screening or an incident myocardial infarction in the 6 months before screening; and those with cardiac arrhythmias (including QTcF: ≥450 ms for men and ≥470 ms for women) that require long-term Arrhythmia (including QTcF: ≥450 ms in men and ≥470 ms in women) requiring long-term use of antiarrhythmic drugs and New York Heart Association class ≥II cardiac insufficiency; 10. Urine protein ≥++ and confirmed 24-hour urine protein quantification >1.0 g; 11. long-standing unhealed wounds or incompletely healed fractures; 12. Imaging showing that the tumor has invaded the periphery of a vital blood vessel or if, in the judgment of the investigator, the patient's tumor has a very high likelihood of invading a vital blood vessel and causing fatal hemorrhage during treatment; 13. Abnormal coagulation function with a bleeding tendency (14 days before enrollment must be satisfied: INR within normal values without anticoagulants); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogs; and patients treated with an International Normalized Ratio of Prothrombin Time (INR ) ≤ 1.5, low-dose warfarin (1 mg orally once daily) or low-dose aspirin (up to 100 mg daily) for prophylactic purposes are permitted; 14. Have had an arterial/venous thrombotic event within one year before screening, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis (except for venous thrombosis due to intravenous catheterization for pre-chemotherapy, which has resolved in the judgment of the investigator), and pulmonary embolism; 15. For female subjects: non-surgical sterilization or non-menopausal patients who refuse to use a medically approved form of contraception during and for 6 months after study treatment; women of childbearing potential who have had a positive serum or urine pregnancy test within 7 days before study entry, or who are breastfeeding. Male subjects: patients who are non-surgically sterilized and who refuse to use a medically approved form of contraception during and for 6 months after the end of the study treatment period; 16. Concomitant illnesses that, in the judgment of the investigator, are serious enough to jeopardize patient safety or interfere with the patient's ability to complete the study; 17. Other conditions that, in the judgment of the investigator, may affect the conduct of the clinical study and the determination of study results.

研究实施时间：

Study execute time：

从 From 2023-09-28 00:00:00至 To 2026-10-28 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-09-28 00:00:00 至 To 2024-09-28 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 89

Group：

experimental group

Sample size：

干预措施：

HR070803联合5-FU/LV与BP102

干预措施代码：

Intervention：

HR0708035, FU/LV and BP102

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)：

 复旦大学附属肿瘤医院 

单位级别：

 三甲 

Institution
hospital：

Fudan University Shanghai Cancer Center

Level of the institution：

Tertiary A

测量指标：

Outcomes：

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：

疾病控制率

指标类型：

次要指标

Outcome：

disease control rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

缓解持续时间

指标类型：

次要指标

Outcome：

duration of remission

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存期

指标类型：

次要指标

Outcome：

progression free survival

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

overall survival

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生存质量

指标类型：

次要指标

Outcome：

quality of life

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：

粪便

组织：

Sample Name：

faeces

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：

尚未开始

Not yet 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）：

不适用

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

Not available

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）：

不适用

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

Not available

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：

病例记录表

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

Case record form

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：

  2023-09-20 16:17:19