Single Site, Open-label, Dose Escalation Phase I Study of Theliatinib (HMPL-309) 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
- 24
- 试验地点
- 1
- 主要终点
- Safety :the incidence of all adverse events by type and grade, abnormal laboratory changes
研究概览
简要总结
First-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity(DLT), safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of Theliatinib .
详细描述
Theliatinib (HMPL-309) is a new constructive, high effective, high selective, EGFR tyrosine kinase inhibitor. Theliatinib has demonstrated strong inhibitory effects on multiple tumors with overexpressed EGFR or sensitive EGFR mutations. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity(DLT), safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of Theliatinib .
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathology confirmed solid tumors
- •Failed to standard treatment or no standard treatments for uncontrolled, recurrent and/or metastatic advance tumor (whatever previous surgery conditions)
- •Age 18-75
- •Performance status of 0, or 1, and no worse within 7days
- •Life expected >3 months
- •Written informed consent form voluntarily
排除标准
- •Lab testing within 1 week before enrolled, AND<1.5×109/L, platelet<75×109/L, or Hb<9g/dL,
- •Total bilirubin≥1.5× the upper limit of normal,
- •Serum creatinine higher than normal range
- •Diastolic pressure≥150mmHg or systolic pressure≥100mmHg whatever anti-hypertension drug used,
- •Serum potassium (whenever potassium implemented) , serum calcium(ionic or albumin-type calcium) or serum magnesium outside normal ranges(whenever implemented)
- •Within previous 4 weeks treated by systemic anti-tumor therapy, or radiotherapy, immune therapy, biological or hormonal therapy, and clinical trials. But exclude the below therapy, Prostate cancer treated by hormonal therapy such as GnRH analogue or antagonist Hormone replacement therapy or oral contraceptive Palliative radiotherapy for bone metastasis within 2 weeks
- •Prior documental evidence of resistance to(epidermal growth factor receptor-tyrosine kinase inhibitors)
- •Unrecovered from any previous therapy related toxicity to≤ CTCAE(Common Toxicity Criteria for Adverse Effects) 0 or 1or unrecovered from any previous surgery
- •Any CNS(central nervous system) metastasis with uncontrolled symptoms
- •Known dysphagia or drug malabsorption
- •Active infections such as acute pneumonia, hepatitis B active period
- •APTT (activated partial thromboplastin time) and/or INR(international normalized ratio), PT≥2 ULN (the upper limit of normal)(not including patients treated by anticoagulation treatment)
- •ocular surface diseases or dry eye syndrome
- •skin disease with obvious symptoms and signs
- •significant cardiovascular disease, including II-IV atrioventricular block, acute myocardial infarction within 6 months, significant angina or Coronary artery bypass graft
- •Known existing interstitial lung disease
- •Female patients who are pregnant or feeding, or childbearing potential patient with pregnant testing positive
- •Any abnormal of clinical and laboratory so that patients unsuitable to attend the trial sine in the opinion of the investigator
- •Patients unable to comply with the protocol since significant psychological or psychogenic abnormal
研究组 & 干预措施
Theliatinib
Theliatinib investigational product once a day (QD) will be orally administrated on a 28-day cycle There are 5 dose cohorts,including120mg/160mg/200mg/220mg/300mg, QD in the dose escalation stage .
干预措施: Theliatinib (Drug)
结局指标
主要结局
Safety :the incidence of all adverse events by type and grade, abnormal laboratory changes
时间窗: from day 1 of first dosing to 30days after permanent discontinuation of Thialitinib
for each patient, adverse events are collected from the date of consent until 30 days after trial discontinuation
次要结局
- Area under the plasma concentration versus time curve (AUC)(Day 1-3 Single Dose and Day 1-28 Steady State)
- Peak Plasma Concentration (Cmax)(Day 1-3 Single Dose and Day 1-28 Steady State)