Phase I Study of Safety and Pharmacokinetics of Sulfatinib(HMPL-012) 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
- 71
- 试验地点
- 1
- 主要终点
- To assess number of participants with adverse events as a measure of safety and tolerability during dose escalating
研究概览
简要总结
Sulfatinib (HMPL-012) is a novel oral small molecule that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and inhibits FGFR kinase activity 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 recommended dose for phase II ,to evaluate the pharmacokinetics , safety and preliminary anti-tumor activity of HMPL-012 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-012 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 monthly 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 0-2
- •Standard regimen failed or no standard regimen available
- •Life expectancy of more than 12 weeks
- •LVEF ≥ 50%
排除标准
- •Pregnant or lactating women
- •Adequate hepatic, renal, heart, and hematologic functions (platelets <75 × 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
- •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
- •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
Sulfatinib capsule
cohort 1: Sulfatinib single oral dosing;after 7days,Sulfatinib continuous oral dosing ( once a day) 28days as a cycle.
干预措施: Sulfatinib (Drug)
结局指标
主要结局
To assess number of participants with adverse events as a measure of safety and tolerability during dose escalating
时间窗: 1-28days after every drug administration
The primary endpoint is evaluation of safety during the first 28-day cycle 1 of therapy following the initiation of multiple dosing of HMPL-012. 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
- To measure the plasma concentration of HMPL-012 in single and repeated doses(Day 1-3 Single Dose and Day 1-56 Steady State)