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

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ClinicalTrials.gov Identifier: NCT02590952
Recruitment Status : Completed
First Posted : October 29, 2015
Last Update Posted : February 17, 2020
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE October 14, 2013
First Posted Date  ICMJE October 29, 2015
Last Update Posted Date February 17, 2020
Actual Study Start Date  ICMJE October 31, 2011
Actual Primary Completion Date April 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 5, 2015)
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2015)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2015)
  • Objective Response Rate [ Time Frame: An average of one year ]
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2015)
  • Objective Response Rate [ Time Frame: An average of one year ]
  • 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. ]
    3. 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.
  • 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. ]
    3. 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I Study of Epitinib(HMPL-813) in Patients With Advanced Solid Tumors
Official Title  ICMJE An Open-label, Multi-Centered, Dose Escalation Phase Ib Study (Expansion Stage) of Epitinib (HMPL-813) in Patients With Advanced Solid Tumors
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: 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.
Other Name: HMPL-813
Study Arms  ICMJE Experimental: Epitinib
Epitinib is a capsule in the form of 5mg,20 mg, and 40 mg. Route: oral (daily)
Intervention: Drug: Epitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 11, 2019)
108
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2015)
40
Actual Study Completion Date  ICMJE April 30, 2019
Actual Primary Completion Date April 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02590952
Other Study ID Numbers  ICMJE 2010-813-00CH1
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Rongjun Liu, M.D. Hutchison Medipharm Limited
PRS Account Hutchison Medipharma Limited
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP