Study of Theliatinib (HMPL-309) in Patients With Advanced Solid Tumor

Cancer Clinical Trial

Official title:

Single Site, Open-label, Dose Escalation Phase I Study of Theliatinib (HMPL-309) in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02601248
• Other study ID #: 2010-309-00CH1
• Status: Completed
• Phase: Phase 1
• Start date: October 2012
• Est. completion date: May 2016

Study information

• Verified date: February 2020
• Source: Hutchison Medipharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

• 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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Theliatinib
Theliatinib is a tablet in the form of 25 mg ,10mg and 100 mg,oral,once daily

Locations

Country	Name	City	State
China	Tianjin Cancer Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety :the incidence of all adverse events by type and grade, abnormal laboratory changes	for each patient, adverse events are collected from the date of consent until 30 days after trial discontinuation	from day 1 of first dosing to 30days after permanent discontinuation of Thialitinib
Secondary	Area under the plasma concentration versus time curve (AUC)	Based on single-dose PK result, multi-dose stage subjects take HMPL-309 once a day or twice a day, PK samples are collected of a single oral dose of HMPL-309 on Day 1 to Day 3. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5,2,4,6,8 hour time points on days 1,15,21of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2,8,16,and 22 of the first 28-Day cycle of therapy	Day 1-3 Single Dose and Day 1-28 Steady State
Secondary	Peak Plasma Concentration (Cmax)	Based on single-dose PK result, multi-dose stage subjects take HMPL-309 once a day or twice a day, PK samples are collected of a single oral dose of HMPL-309 on Day 1 to Day 3. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5,2,4,6,8 hour time points on days 1,15,21of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2,8,16,and 22 of the first 28-Day cycle of therapy	Day 1-3 Single Dose and Day 1-28 Steady State