Phase I Study of Safety and Pharmacokinetics of Fruquintinib(HMPL-013) in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety in the first 28-Days of Therapy
研究概览
简要总结
Fruquintinib (HMPL-013) is a novel oral small molecule that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics , safety and preliminary anti-tumor activity of HMPL-013 at single doses and multiple doses .
详细描述
This will be an open-label, phase I study. This study will evaluate the safety and pharmacokinetics of HMPL-013 after a single administration followed by a 28-Day continuous course of therapy; evaluate the safety and preliminary efficacy in an open-label administration of at the MTD. All subjects of this study will be permitted to continue therapy with only safety monitoring and bimonthly assessments for progression, if the product is well tolerated and the subject has stable disease or better.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histological or cytological confirmed solid malignant tumor
- •ECOG performance status of 0-1
- •Standard regimen failed or no standard regimen available
- •Life expectancy of more than 12 weeks
- •LVEF ≥ 50%
- •Duration from the last therapy is more than 4 weeks for operation or radiotherapy; more than 4 weeks for prior systemic treatment
- •Adequate hepatic, renal, heart, and hematologic functions (platelets > 80 × 109/L, neutrophil > 1.5 × 109/L, hemoglobin > 90g/dl ,serum creatinine within upper limit of normal(ULN), total bilirubin and serum transaminase within upper limit of normal(ULN), and PT, APTT, TT, Fbg normal
- •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 uncontrolled 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 VEGF/VEGFR inhibition
- •Disability of serious uncontrolled intercurrence infection
- •Proteinuria ≥ 2+
- •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
Fruquintinib capsule
cohort 1: fruquintinb continuous oral dosing (1mg once a day) cohort 2: fruquintinb continuous oral dosing (2mg once a day) cohort 3: fruquintinb continuous oral dosing (4mg once a day) cohort 4: fruquintinb continuous oral dosing (6mg once a day) cohort 5: fruquintinb continuous oral dosing (5mg once a day) cohort 6: fruquintinb oral dosing, 3 weeks on/1 week off (5mg once a day) cohort 7: fruquintinb oral dosing, 3 weeks on/1 week off (6mg once a day)
干预措施: Fruquintinib (Drug)
结局指标
主要结局
Safety in the first 28-Days of Therapy
时间窗: 28-Days after Permanent Discontinuation of HMPL-013
The primary endpoint is evaluation of safety during the first 28-day cycle of therapy following the initiation of multiple dosing of HMPL-013. The safety variables to be evaluated in this study are adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology , and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for protein), and electrocardiograms (ECGs) in triplicate.
次要结局
- Objective Response Rate （ORR)(every 8 weeks until end of treatment)
- Pharmacokinetic Assessments for AUC, Cmax and Tmax(Day 1-3 Single Dose and Day 1-28 Steady State)