A Phase I Study of Epitinib(HMPL-813) in Patients With Advanced Solid Tumors

NCT02590952 | Completed Phase 1

• 1 other identifier: 2010-813-00CH1
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

Epitinib (HMPL-813) is a selective EGFR tyrosine kinase inhibitor. Epitinib has demonstrated strong inhibitory effects on multiple tumors with overexpressed EGFR or sensitive EGFR mutations in pre-clinical setting. 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 Epitinib.

Conditions

Solid Tumor

Keywords

safety, PK

Outcome Measures

Primary Outcomes (1)

• incidence of all types/grades of adverse events

  for each patient, adverse events are collected from the date of consent until 30 days after trial discontinuation

  from first patient in till 30 days after the last patient last visit. It is estimated that last patient last visit happens in Oct 2016.

Secondary Outcomes (3)

• Objective Response Rate

  An average of one year

• Area under the plasma concentration versus time curve (AUC)

  At single-dose stage (day 1-day 7): predose, 0.5,1, 2, 3, 4, 5, 6, 8,12,24, 36, 48, 72, 144 hours post-dose.

• Peak Plasma Concentration (Cmax)

  At single-dose stage (day 1-day 7): predose, 0.5,1, 2, 3, 4, 5, 6, 8,12,24, 36, 48, 72, 144 hours post-dose.

Study Arms (1)

Epitinib

EXPERIMENTAL

Epitinib is a capsule in the form of 5mg,20 mg, and 40 mg. Route: oral (daily)

Drug: Epitinib

Interventions

Epitinib DRUG

The starting daily dose is 20 mg. Dose escalation will follow daily dose of 40 mg,80 mg, 120 mg, 160 mg, 200 mg, and 250 mg. A 3+3 design applies to this study. Patients will continue taking Epitinib until they experience intolerable adverse events or their diseases are confirmed to be progressed.

Also known as: HMPL-813

Epitinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 18-70
• ECOG 0-2, and no worse within 7days
• Life expected \> 12 weeks
• written informed consent form voluntarily
• EGFR sensitizing mutation in exon 19 deletion or exon 21(L858R).
• Histologically or cytologically confirmed advanced NSCLC with brain metastasis. No prior brain radiotherapy or brain metastasis progressed after brain radiotherapy delivered assessed by RECIST 1.1.
• No prior EGFR-TKI treatment. Or subjects who treated with EGFR-TKI developed brain lesions during EGFR-TKI therapy or the existing brain lesions progressed but with stable extra-cranial lesions.
• Treatment failure of prior systemic chemotherapy for locally advanced or metastasized NSCLC or intolerance to chemotherapy. Or subjects with disease relapse after treated with adjuvant or neo-adjuvant chemotherapy.
• With at least one measurable disease ( RECIST 1.1).

You may not qualify if:

• Lab testing within 2 weeks before enrolled, AND ANC\<1.5×10 9/L, platelet\<75×10 9/L, or Hb\<9g/dL,
• Serum Total Bilirubins \> ULN, ALT/AST≥ULN without liver metastasis, or ALT/AST≥2.5ULN with liver metastasis
• Serum creatinine \>1.5ULN or creatinine clearance \<40ml/min
• Diastolic systolic pressure≥140mmHg or systolic diastolic pressure≥90mmHg whatever anti-hypertension drug used,
• Serum potassium \<4.0mmol/L(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.
• Unrecovered from any previous therapy related toxicity to CTCAE 0 or 1or unrecovered from any previous surgery
• Known dysphagia or drug malabsorption
• Active infections such as acute pneumonia, hepatitis B immune-active periodphase
• ocular surface diseases or dry eye syndrome
• skin disease with obvious symptoms and signs
• significant cardiovascular disease, including II-IV atrioventricular block, and acute myocardial infarction within 6 months, significant angina or Coronary artery bypass graft within 6 months
• 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

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

Guangdong General Hospital

Guangzhou, 510080, China

Location

Related Publications (1)

• Zhou Q, Wang M, Zhang H, Hong Q, Liu X, Lu P, Su W, Wu YL. Safety and Efficacy of Epitinib for EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Open-Label Multicentre Dose-Expansion Phase Ib Study. Clin Lung Cancer. 2022 Sep;23(6):e353-e361. doi: 10.1016/j.cllc.2022.03.014. Epub 2022 May 7.

  PMID: 35654732 DERIVED

Study Officials

• Rongjun Liu, M.D.

  Hutchison Medipharm Limited

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2013
• First Posted: October 29, 2015
• Study Start: October 31, 2011
• Primary Completion: April 30, 2019
• Study Completion: April 30, 2019
• Last Updated: February 17, 2020

Record last verified: 2019-02

Locations

CN (1)