Single Site, Open-label, Dose Escalation Phase I Study of Theliatinib (HMPL-309) in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Theliatinib
- Conditions
- Cancer
- Sponsor
- Hutchison Medipharma Limited
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Safety :the incidence of all adverse events by type and grade, abnormal laboratory changes
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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 .
Detailed Description
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 .
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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 .
Intervention: Theliatinib
Outcomes
Primary Outcomes
Safety :the incidence of all adverse events by type and grade, abnormal laboratory changes
Time Frame: 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
Secondary Outcomes
- 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)