Open-label, Dose Escalation Phase I Study of Theliatinib (HMPL-309,Xiliertinib) in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- incidence of all types/grades of adverse events
研究概览
简要总结
A Phase I, open-label, multicenter dose-escalation study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of hmpl-309 in patients with advanced solid tumors
详细描述
There are two stages to this study: a dose-escalation stage and a dose-expansion stage.
Dose-escalation stage: hmpl-309 administered orally once every day(QD) to patients with locally advanced or metastatic solid tumors for whom standard therapy either does not exist or has proven to be ineffective or intolerable. Dose-expansion stage: hmpl-309 administered orally 300mg once every day(QD) to patients which is only for patients with EGFR positive oesophageal carcinoma.
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)
- •Dose-escalation stage:
- •<300mg/day cohort no requiremnet for pathological pattern >300mg/day cohort required NCSLC, head and net squamous carcinoma, or oesophageal carcinoma Dose-expansion stage required oesophageal carcinoma
- •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, hemoglobin <9 g/dL or , platelet count < 750,000/mm3 and<150000/mm3,
- •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(gonadotropin-releasing hormone) analogue or antagonist Hormone replacement therapy or oral contraceptive Palliative radiotherapy for bone metastasis within 2 weeks
- •Prior documental evidence of resistance to EGFR-TKI (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 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
Single Group Assignment
Theliatinib investigational product once a day (QD) will be orally administrated on a 28-day cycle There are 7 dose cohorts,including120mg/160mg/200mg/220mg/300mg/400mg/500mg, QD in the dose escalation stage .
干预措施: Theliatinib (Drug)
结局指标
主要结局
incidence of all types/grades of adverse events
时间窗: from first patient in till 30 days after the last patient last visit
for each patient, adverse events are collected from the date of consent until 30 days after trial discontinuation
次要结局
未报告次要终点