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

NCT ID: NCT02590952

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2019-04-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epitinib

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

Group Type: EXPERIMENTAL

Epitinib

Intervention Type: 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.

Interventions

Epitinib

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.

Intervention Type: DRUG

Other Intervention Names

HMPL-813

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 18-70
• 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).

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rongjun Liu, M.D.

Role: STUDY_CHAIR

Hutchison Medipharm Limited

Locations

Guangdong General Hospital

Guangzhou, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 35654732 (View on PubMed)

Other Identifiers

2010-813-00CH1

Identifier Type: -

Identifier Source: org_study_id