A Phase I Study of Epitinib(HMPL-813) in Patients With Advanced Solid Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Epitinib Epitinib is a capsule in the form of 5mg,20 mg, and 40 mg. Route: oral (daily) |
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 Names:
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Outcome Measures
Primary Outcome Measures
- incidence of all types/grades of adverse events [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 Outcome Measures
- 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.]
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) [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histopathology confirmed solid tumors
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Failed to standard treatment or no standard treatments for uncontrolled, recurrent and/or metastatic advance tumor (whatever previous surgery conditions)
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Age 18-70
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ECOG 0-2, and no worse within 7days
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Life expected > 12 weeks
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written informed consent form voluntarily
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For dose expansion cohort, subjects must be eligible for the following inclusion criteria:
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EGFR sensitizing mutation in exon 19 deletion or exon 21(L858R).
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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.
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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.
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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.
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With at least one measurable disease ( RECIST 1.1).
Exclusion Criteria:
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Lab testing within 2 weeks before enrolled, AND ANC<1.5×10 9/L, platelet<75×10 9/L, or Hb<9g/dL,
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Serum Total Bilirubins > ULN, ALT/AST≥ULN without liver metastasis, or ALT/AST≥2.5ULN with liver metastasis
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Serum creatinine >1.5ULN or creatinine clearance <40ml/min
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Diastolic systolic pressure≥140mmHg or systolic diastolic pressure≥90mmHg whatever anti-hypertension drug used,
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Serum potassium <4.0mmol/L(whenever potassium implemented), serum calcium(ionic or albumin-type calcium) or serum magnesium outside normal ranges(whenever implemented)
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Within previous 4 weeks treated by systemic anti-tumor therapy, or radiotherapy, immune therapy, biological or hormonal therapy, and clinical trials.
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Unrecovered from any previous therapy related toxicity to CTCAE 0 or 1or unrecovered from any previous surgery
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Known dysphagia or drug malabsorption
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Active infections such as acute pneumonia, hepatitis B immune-active periodphase
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ocular surface diseases or dry eye syndrome
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skin disease with obvious symptoms and signs
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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
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Female patients who are pregnant or feeding, or childbearing potential patient with pregnant testing positive
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Any abnormal of clinical and laboratory so that patients unsuitable to attend the trial sine in the opinion of the investigator
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Patients unable to comply with the protocol since significant psychological or psychogenic abnormal
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Guangdong General Hospital | Guangzhou | China | 510080 |
Sponsors and Collaborators
- Hutchison Medipharma Limited
Investigators
- Study Chair: Rongjun Liu, M.D., Hutchison Medipharm Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2010-813-00CH1