ChiCTR2400088697 版本V1.0 版本创建时间2024/08/26 08:35:41 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：

ChiCTR2400088697 

最近更新日期：

Date of Last Refreshed on：

2024-08-26 08:34:46 

注册时间：

Date of Registration：

2024-08-26 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

伊立替康脂质体联合呋喹替尼治疗二线及以上复发性结直肠癌的探索性研究

Public title：

An exploratory study of Irinotecan liposome combined with Fruquintinib in the treatment of second-line and above recurrent colorectal cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

伊立替康脂质体联合呋喹替尼治疗二线及以上复发性结直肠癌的探索性研究

Scientific title：

An exploratory study of Irinotecan liposome combined with Fruquintinib in the treatment of second-line and above recurrent colorectal cancer

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：

韩春 

研究负责人：

韩春 

Applicant：

Han Chun 

Study leader：

Chun Han 

申请注册联系人电话：

Applicant telephone：

+86 10 81215528

研究负责人电话：

Study leader's telephone：

+86 10 81215607

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：

hanchun301@sina.com

研究负责人电子邮件：

Study leader's E-mail：

hanchun301@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：

北京市大兴区明春东路25号

研究负责人通讯地址：

优龙路明春苑甲3号

Applicant address：

Mingchun Dong Road, No. 25, Daxing, Beijing

Study leader's address：

No. 3 MingChunYuan, Youlong Road, DaXing District, Beijng, 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：

北京美中爱瑞肿瘤医院

Applicant's institution：

Beijing arion cancer center

研究负责人所在单位：

北京美中爱瑞肿瘤医院

Affiliation of the Leader：

Arion Cancer Center

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

AEC2024-003-002

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：

北京美中爱瑞肿瘤医院伦理委员会

Name of the ethic committee：

Arion Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2024-08-14 00:00:00

伦理委员会联系人：

张琪

Contact Name of the ethic committee：

Zhang Qi

伦理委员会联系地址：

优龙路明春苑甲3号

Contact Address of the ethic committee：

No. 3 MingChunYuan, Youlong Road, DaXing District, Beijng, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 10 81215510

伦理委员会联系人邮箱：

Contact email of the ethic committee：

joy.zhang@arion.care

研究实施负责（组长）单位：

北京美中爱瑞肿瘤医院

Primary sponsor：

Arion Cancer Center

研究实施负责（组长）单位地址：

优龙路明春苑甲3号

Primary sponsor's address：

No. 3 MingChunYuan, Youlong Road, DaXing District, Beijng, 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)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

北京美中爱瑞肿瘤医院

具体地址：

优龙路明春苑甲3号

Institution
hospital：

Arion Cancer Center

Address：

No. 3 MingChunYuan, Youlong Road, DaXing District, Beijng, China

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

self funded

Target disease：

Pathologically confirmed metastatic or unresectable colorectal cancer; Received >2 lines of systemic anti-cancer therapy in the past

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 II期临床试验 

Study phase：

2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

本研究旨在评估伊立替康脂质体联合呋喹替尼治疗二线及以上复发性结直肠癌的安全性和有效性  

Objectives of Study：

This study aims to evaluate the safety and efficacy of irinotecan liposome combined with fruquintinib in the treatment of second-line and above recurrent 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.受试者自愿加入本研究，签署知情同意书，依从性良好，能配合随访； 2.年龄≥18岁，性别不限（以签署知情同意当日计算）； 3.经病理学确诊的转移性或不可切除的结直肠癌（所有其他组织学类型都排除在外）； 4.既往接受过≥2线的系统抗肿瘤治疗，若既往治疗方案含伊立替康，则距离最后一次使用伊立替康至少6个月； 5.根据 RECIST v1.1 标准，至少具有一个可测量的靶病灶； 6.ECOG评分：0～1 分； 7.预计生存期 ≥3个月； 8.主要器官功能正常，即符合下列标准:（1） 血常规检查需符合以下标准（14天内未接受任何血液成分、细胞生长因子的情况下)： A.血红蛋白(Hb) ≥ 80 g/L； B.中性粒细胞计数（ANC）≥1.5×10^9/L； C.白细胞计数（WBC）≥3.0×10^9/L D.血小板计数(PLT) ≥ 100 ×10^9/L； （2） 生化检查需符合以下标准： A.总胆红素(TBIL) ≤ 1.5 ×正常值上限(ULN)； B.谷丙转氨酶(ALT)和谷草转氨酶(AST) ≤3 × ULN，而对于肝转移患者则< 5 ×ULN； C.血清肌酐(Cr) ≤ 1.5 × ULN或者内生肌酐清除率≥50ml/min（Cockcroft-Gault公式）； D.尿常规检测结果显示尿蛋白＜2+或24小时尿蛋白定量＜1g； （3）多普勒超声评估：左室射血分数 (LVEF) ≥正常值低限 (50%)； （4）凝血功能：国际标准化比率（INR）≤1.5×ULN且活化的部分凝血活酶时间≤1.5×ULN； 9.育龄女性应为同意在研究期间和研究结束后6个月内必须采用有效的避孕措施；在研究入组前的 7 天内血清或尿妊娠试验阴性，且必须为非哺乳期患者；男性应同意在研究期间和研究期结束后6个月内必须采用避孕措施的患者；

Inclusion criteria

1.The subjects voluntarily participated in this study, signed the informed consent, had good compliance, and were able to cooperate with the follow-up; 2.Age ≥ 18 years old, male or female (calculated on the day of signing the informed consent); 3.Pathologically confirmed metastatic or unresectable colorectal cancer (all other histological types were excluded); 4.Patients who have received ≥2 lines of systemic anti-cancer therapy in the past. If the previous treatment regimen contained irinotecan, it must have been at least 6 months since the last use of irinotecan; 5.At least one measurable target lesion according to RECIST v1.1; 6.ECOG score: 0-1; 7.Expected survival time ≥3 months; 8.The major organs function normally, that is, meet the following criteria: (1) Routine blood tests must meet the following criteria (without receiving any blood components or cell growth factors within 14 days): A. Hemoglobin (Hb) ≥ 80 g/L; B. Neutrophil count (ANC) ≥ 1.5×10^9/L; C. White blood cell count (WBC) ≥ 3.0×10^9/L D. Platelet count (PLT) ≥ 100 ×10^9/L; (2) Biochemical tests must meet the following criteria: A. Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); B. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, and for patients with liver metastasis, < 5 × ULN; C. Serum creatinine (Cr) ≤ 1.5 × ULN or endogenous creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); D. Urinalysis results show urine protein <2+ or 24-hour urine protein <1g; (3) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%); (4) Coagulation function: international normalized ratio (INR) ≤1.5×ULN and activated partial thromboplastin time ≤1.5×ULN; 9.Women of childbearing age must agree to use effective contraceptive measures during the study and within 6 months after the study ends; serum or urine pregnancy test is negative within 7 days before study enrollment, and must be non-breastfeeding patients; men must agree to use contraceptive measures during the study and within 6 months after the study ends.

排除标准：

1.对伊立替康脂质体、呋喹替尼中任何成份过敏者； 2.5年内患有其它恶性肿瘤，但是已治愈的皮肤基底细胞癌和宫颈原位癌除外； 3.入组前四周内参加过其他药物临床试验； 4.BRAF突变或N-Ras突变； 5.严重的胃肠功能紊乱（有出血、梗阻；大于2级的炎症；大于1级的腹泻）； 6.入组前6个月内有胃肠道穿孔、胃肠瘘、腹腔内脓肿以及非胃肠道瘘（如气管-食管瘘）者； 7.有临床症状的腹水，需要穿刺、引流的患者（仅影像学显示少量腹水且可控制，但不伴有临床症状者除外）； 8.具有明确的胃肠道出血倾向的患者，包括下列情况：有局部活动性溃疡病灶，且大便潜血【（＋＋）不可入组】；2个月内有黑便、呕血病史者； 9.已知有间质性肺病，仅影像学显示的间质性改变除外； 10.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，入组前28天内必须进行增强CT或增强核磁共振（MRI）检查，评估后为稳定期脑转移的患者可入组； 11.入组前 2 周内伴随用药中含有 CYP3A4、CYP2C8 强抑制剂/强诱导剂或 UGT1A1 强抑制剂； 12.患有高血压且经单一降压药物治疗?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；?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； 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）≤ 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.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个月内采用种经医学认可的避孕措施的患者； 15.合并活动性乙型肝炎（乙肝表面抗原阳性且HBV DNA≥500IU/mL），丙型肝炎（丙肝抗体阳性，且HCV-RNA高于正常值上限）；已知有获得性免疫缺陷综合征（艾滋病）或 HIV 检测阳性者，活动性梅毒感染者； 16.患者有活动性感染、入组前1周内有不明原因发热≥38.5℃、或筛选期白细胞计数>15×109/L；入组前2周内口服或静脉给予治疗性抗生素（用药时间不超过 48 小时静脉给予的预防性抗生素除外）； 17.既往有明确的神经或精神障碍史，包括癫痫或痴呆； 18.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； 19.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.Allergic to any ingredient in irinotecan liposome or furiquintinib; 2.Suffering from other malignant tumors within 5 years, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix; 3.Participated in other drug clinical trials within four weeks before enrollment; 4.BRAF mutation or N-Ras mutation; 5.Severe gastrointestinal dysfunction (bleeding, obstruction; inflammation greater than grade 2; diarrhea greater than grade 1); 6.Patients with gastrointestinal perforation, gastrointestinal fistula, intra-abdominal abscess, and non-gastrointestinal fistula (such as tracheoesophageal fistula) within 6 months before enrollment; 7.Patients with clinical symptoms of ascites who require puncture and drainage (except those with only a small amount of ascites shown by imaging and which is controllable but without clinical symptoms); 8.Patients with a clear tendency of gastrointestinal bleeding, including the following: those with local active ulcer lesions and occult blood in stool [(++) cannot be included]; those with a history of black stools and hematemesis within 2 months; 9.Known interstitial lung disease, except for interstitial changes seen only on imaging; 10.Patients with known central nervous system metastasis or a history of central nervous system metastasis before screening, and patients with clinically suspected central nervous system metastasis must undergo enhanced CT or enhanced magnetic resonance imaging (MRI) examination within 28 days before enrollment. Patients with stable brain metastasis after evaluation can be enrolled; 11.Concomitant medications containing strong inhibitors/inducers of CYP3A4, CYP2C8, or strong inhibitors of UGT1A1 within 2 weeks before enrollment; 12.Patients with hypertension that cannot be well controlled by single antihypertensive drug treatment (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); patients with a history of unstable angina pectoris; patients newly diagnosed with angina pectoris within 3 months before screening or myocardial infarction within 6 months before screening; patients with arrhythmia (including QTcF: male ≥450 ms, female ≥470 ms) requiring long-term use of antiarrhythmic drugs and New York Heart Association grade ≥ II heart failure; 13.Abnormal coagulation function and bleeding tendency (must meet the following conditions 14 days before enrollment: INR is within the normal range without the use of anticoagulants); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogs; under the premise that the international normalized ratio (INR) of prothrombin time is ≤ 1.5, low-dose warfarin (1 mg orally, once a day) or low-dose aspirin (daily dose not exceeding 100 mg) is allowed for preventive purposes; 14.For female subjects: non-surgically sterilized or non-postmenopausal patients who refuse to use a medically recognized contraceptive method during the study treatment and within 6 months after the study treatment period; women of childbearing age who have a positive serum or urine pregnancy test within 7 days before study enrollment or are breastfeeding. Male subjects: patients who are non-surgically sterilized and refuse to use a medically recognized contraceptive method during the study treatment and within 6 months after the study treatment period; 15.Patients with active hepatitis B (positive hepatitis B surface antigen and HBV DNA ≥ 500 IU/mL), hepatitis C (positive hepatitis C antibody and HCV-RNA higher than the upper limit of normal value); patients with acquired immunodeficiency syndrome (AIDS) or HIV positive test, active syphilis infection; 16.Patients with active infection, unexplained fever ≥38.5℃ within 1 week before enrollment, or white blood cell count >15×109/L during screening period; oral or intravenous therapeutic antibiotics within 2 weeks before enrollment (except for preventive antibiotics given intravenously for no more than 48 hours); 17.A clear history of neurological or psychiatric disorder, including epilepsy or dementia; 18.According to the investigator's judgment, there are serious concomitant diseases that may endanger the patient's safety or affect the patient's completion of the study; 19.The researcher determines other situations that may affect the conduct of the clinical study and the determination of the study results;

研究实施时间：

Study execute time：

从 From 2024-08-21 00:00:00至 To 2027-08-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-08-26 00:00:00 至 To 2026-08-31 00:00:00  

干预措施：

Interventions：

组别：

治疗组

样本量：

30

Group：

Treatment group

Sample size：

干预措施：

盐酸伊立替康脂质体联合呋喹替尼

干预措施代码：

Intervention：

Irinotecan hydrochloride liposome combined with fuquintinib

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)：

北京美中爱瑞肿瘤医院 

单位级别：

三级医院 

Institution
hospital：

Arion Cancer Center

Level of the institution：

Tertiary

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

次要指标

Outcome：

Objective response rate，ORR

Type：

Secondary indicator

测量时间点：

所有病例观察到肿瘤进展事件时

测量方法：

指按照相应标准评估最佳总体疗效为CR或PR的受试者人数的比例。若疗效达CR、PR，受试者须在首次评价4周后进行复查确认

Measure time point of outcome：

Tumor progression events were observed in all cases

Measure method：

The proportion of subjects whose best overall response is assessed as CR or PR according to the appropriate criteria. If the efficacy reaches CR or PR, the subject shall be re-evaluated 4 weeks after the initial evaluation

指标中文名：

缓解持续时间

指标类型：

次要指标

Outcome：

During of response，DoR

Type：

Secondary indicator

测量时间点：

所有病例观察到肿瘤进展事件时

测量方法：

记录所有病例从第一次记录肿瘤缓解（即CR或PR，按照相应标准）到第一次记录到疾病进展（PD，按照相应标准）或因任何原因导致死亡的时间，以先出现者为准，计算中位数

Measure time point of outcome：

Tumor progression events were observed in all cases

Measure method：

All cases were recorded from the time when the tumor was first recorded in remission (i.e., CR or PR, according to the appropriate criteria) to the time when the disease progressed (PD, according to the appropriate criteria) or died from any cause, whichever came first, with the median calculated

指标中文名：

无进展生存期

指标类型：

次要指标

Outcome：

Progression-free survival，PFS

Type：

Secondary indicator

测量时间点：

所有病例观察到肿瘤进展事件时

测量方法：

记录所有病例从入组到第一次记录肿瘤进展（按照相应标准评定，无论是否继续治疗）或任何原因导致死亡的时间，以先出现者为准，计算中位数

Measure time point of outcome：

Tumor progression events were observed in all cases

Measure method：

The median time from enrollment to first recording of tumor progression (as assessed by the appropriate criteria, regardless of whether treatment continued) or death from any cause was calculated for all cases, whichever came first

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

Overall survival，OS

Type：

Secondary indicator

测量时间点：

所有病例观察到死亡事件时

测量方法：

记录所有病例从入组至任何原因导致死亡的时间，计算中位数

Measure time point of outcome：

Death was observed in all cases

Measure method：

Time from enrollment to death from any cause

指标中文名：

不良事件

指标类型：

次要指标

Outcome：

Adverse event

Type：

Secondary indicator

测量时间点：

所有病例观察到死亡事件时

测量方法：

记录所有病例从入组后到观察到死亡事件时所发生的所有不良反应，并计算发生率

Measure time point of outcome：

Death was observed in all cases

Measure method：

All adverse events that occurred in all cases from the time of enrollment until death was observed were recorded and the incidence was calculated

指标中文名：

疾病控制率

指标类型：

主要指标

Outcome：

Disease control rate，DCR

Type：

Primary indicator

测量时间点：

所有病例观察到肿瘤进展事件时

测量方法：

按照相应标准评定最佳总体疗效为CR、PR和疾病稳定（SD）的受试者所占的比例

Measure time point of outcome：

Tumor progression events were observed in all cases

Measure method：

Proportion of subjects whose best overall response was rated as CR, PR, and stable disease (SD) according to the corresponding criteria

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

Sample Name：

NA

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

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 80 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：

无

Blinding：

None

是否共享原始数据：

IPD sharing

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）：

不共享数据

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

Not sharing original data

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：

无/No

注册人：

Name of Registration：

  2024-08-26 08:34:46