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NCT Number: NCT02590952

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

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.

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Key information

Conditions

Solid Tumor

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Guangdong General Hospital

Guangzhou, 510080, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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
  • For dose expansion cohort, subjects must be eligible for the following inclusion criteria:
  • 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

Treatment and study plan

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.

Other names: HMPL-813

Primary outcomes

  1. incidence of all types/grades of adverse events

    Time frame: 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.

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

Secondary outcomes

  1. Objective Response Rate

    Time frame: An average of one year

  2. Area under the plasma concentration versus time curve (AUC)

    Time frame: 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.

    Based on single-dose PK result, multi-dose stage subjects take epitinib either once a day or twice a day. For twice a day epitinib uptake, on day 1/14/28, PK samples are collected predose, 1, 4, 8, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 2/3/7, PK samples are collected predose, 4, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 15/29/56, PK samples are collected predose in the morning.

    For once a day epitinib uptake, on day 1/14/28 PK samples are collected predose, 0.5, 1, 2, 4, 6, 8, 12 hours post-dose. On day 7, PK samples are collected predose and 4 hours post-dose. On day 2/15/29/56, PK samples are collected predose in the morning.

  3. Peak Plasma Concentration (Cmax)

    Time frame: 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.

    Based on single-dose PK result, multi-dose stage subjects take epitinib either once a day or twice a day. For twice a day epitinib uptake, on day 1/14/28, PK samples are collected predose, 1, 4, 8, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 2/3/7, PK samples are collected predose, 4, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 15/29/56, PK samples are collected predose in the morning.

    For once a day epitinib uptake, on day 1/14/28 PK samples are collected predose, 0.5, 1, 2, 4, 6, 8, 12 hours post-dose. On day 7, PK samples are collected predose and 4 hours post-dose. On day 2/15/29/56, PK samples are collected predose in the morning.

Sponsors and collaborators

Lead sponsor

Hutchison Medipharma Limited

Industry

Registry information

Official study title

An Open-label, Multi-Centered, Dose Escalation Phase Ib Study (Expansion Stage) of Epitinib (HMPL-813) in Patients With Advanced Solid Tumors

Important dates

Study start
2011
Primary completion
2019
Study completion
2019
First posted
Oct 29, 2015
Registry last updated
Feb 17, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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