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

• ClinicalTrials.gov Identifier: NCT02601248
• Recruitment Status: Completed
• First Posted: November 10, 2015
• Last Update Posted: February 13, 2020
• Sponsor: Hutchison Medipharma Limited
• Information provided by (Responsible Party): Hutchmed ( Hutchison Medipharma Limited )

Tracking Information

• First Submitted Date: October 14, 2013
• First Posted Date: November 10, 2015
• Last Update Posted Date: February 13, 2020
• Study Start Date: October 2012
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 9, 2015)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 9, 2015)

• Area under the plasma concentration versus time curve (AUC) [ Time Frame: Day 1-3 Single Dose and Day 1-28 Steady State ]
  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
• Peak Plasma Concentration (Cmax) [ Time Frame: Day 1-3 Single Dose and Day 1-28 Steady State ]
  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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Theliatinib (HMPL-309) in Patients With Advanced Solid Tumor
• Official Title: Single Site, Open-label, Dose Escalation Phase I Study of Theliatinib (HMPL-309) in Patients With Advanced Solid Tumors
• 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 .
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer

Intervention

Drug: Theliatinib

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

Other Name: HMPL-309

Study Arms

Experimental: 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: Drug: Theliatinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 31, 2016): 24
• Original Estimated Enrollment (submitted: November 9, 2015): 30
• Actual Study Completion Date: May 2016
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)

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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02601248
• Other Study ID Numbers: 2010-309-00CH1
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hutchmed ( Hutchison Medipharma Limited )
• Original Responsible Party: Same as current
• Current Study Sponsor: Hutchison Medipharma Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Weiguo Su, PhD; Hutchison Medipharm Limited

• PRS Account: Hutchmed
• Verification Date: February 2020