A Randomized, Open-label Phase Ib Trial of Fruquintinib "4mg Once Daily Continuous"Versus "5mg Once Daily 3wks on/1wk Off" in Patients With Metastatic Colorectal Carcinoma as 3rd Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 2
- 主要终点
- safety and tolerability
研究概览
简要总结
Fruquintinib is a novel oral small molecule compound discovered and developed by Hutchison MediPharma that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts.Based on first-in-human study, both 4mg QD and 5mg 3wks on/1wk off are safety and efficacy, this phase Ib study is to evaluable the safety, tolerability and efficacy of these 2 regimens with mCRC failed 2nd therapy or more and to determine the recommended dose and regimen in phase II/III study.
详细描述
This is a phase Ib, randomize, interventional, open-label, multicenter study to provide fruquintinib to subjects diagnosed with metastatic colorectal cancer who have failed after standard therapy and for whom no therapy alternatives exist.
The primary endpoint of this study will be safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 and ≤ 70 years of age , with ≥ 40Kg
- •Histological or cytological confirmed colorectal cancer
- •ECOG performance status of 0-1
- •Standard regimen failed or no standard regimen available
- •Adequate hepatic, renal, heart, and hematologic functions
- •At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
- •Signed and dated informed consent.
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure
排除标准
- •Pregnant or lactating women
- •Any factors that influence the usage of oral administration
- •Evidence of CNS metastasis
- •Intercurrence with one of the following: non-controlled hypertension, coronary artery disease, arrhythmia and heart failure
- •Abuse of alcohol or drugs
- •Less than 4 weeks from the last clinical trial
- •Previous treatment with VEGFR inhibition
- •Disability of serious uncontrolled intercurrence infection
- •Proteinuria ≥ 2+ (1.0g/24hr)
- •Uncontrolled hemorrhage in GI
- •Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack) etc.
- •Within 6 months before the first treatment occurs acute myocardial infarction, acute coronary syndrome or CABG
- •Bone fracture or wounds that was not cured for a long time
- •Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy
研究组 & 干预措施
A- 4mg QD
arm A- fruquintinib 4mg once daily, p.o.,continuous;given in 28-days cycles until disease progress, intolerable toxicity or patients withdrawal of consent
干预措施: fruquintinib (Drug)
B- 5mg once daily, 3wks on/1wk off
arm B-fruquintinb 5mg once daily,p.o.,3 weeks on/1 week off, given in 28-day cycles until disease progress,intolerable toxicity or patients withdrawal of consent
干预措施: fruquintinib (Drug)
结局指标
主要结局
safety and tolerability
时间窗: from day 1 of first dosing to 30days after permanent discontinuation of HMPL-013
The primary objective is evaluation of safety and tolerabilty with 2 regimens. The primary endpoint is the incidence of AEs, SAEs, Gr3/4 AEs and AEs led to dose interruption and dose discontinued
次要结局
- objective response rate(ORR)(every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months)
- pharmacokinetic profiles(Day 1-84 steady state)
- disease control rate (DCR)(every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months)
- progression-free survival (PFS)(every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months)
- overall survival (OS)(every 2 months since end of treatment)