A Phase I, Open Label, Non Randomized, Multicenter, Dose Escalation Clinical Study to Investigate Safety and Tolerability of OPB(Otsuka Pharmaceutical Biwa)-111077 in Subjects With Advanced HCC(Hepatocellular Carcinoma)

Study Overview
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Brief Summary
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This is a Phase I, open label, non randomized, multicenter study designed to investigate the safety and tolerability of escalating doses of OPB-111077 administered orally, once daily in subjects with advanced HCC.

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: OPB-111077


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically or clinically diagnosed HCC by Korean Liver Cancer Study Group (KLCSG) guidelines. Subject who has advanced HCC Documented evidence of unresponsiveness to, intolerance to, or ineligibility for sorafenib, or unavailability of appropriate sorafenib treatment Male or female subject, age at consent ≥20 years and ≤75 years. Life expectancy ≥12 weeks. Subjects who agree that they or their partner(s) will practice contraception during the study period and 3 months (12 weeks) after the completion of study treatment. Subjects informed of the diagnosis of advanced HCC who are fully informed about the content of the study by the Investigator using the written consent form, and give written consent to participate in the study of their own free will. Exclusion Criteria: Past liver transplantation Uncontrollable hepatic encephalopathy or ascites Presence of brain metastases Clinically significant gastrointestinal bleeding in past 6 months or current active gastrointestinal bleeding. Primary malignancy other than HCC Human immunodeficiency virus (HIV) infection Severe or poorly controlled complication that may affect the conduct or results of the study. Use of Interferon preparation within 4 weeks (28 days) before start of study treatment in the present study. Pregnant, nursing, or possibly pregnant women, or women desiring to become pregnant during the study period Other cases judged by the Investigator to be ineligible for participation in the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPB-111077<br>orally, once daily | Drug: OPB-111077<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of OPB-111077 | Number of participants with adverse events as assessed by CTCAE v4.0 | Within the first cycle [24 days] | 
| To investigate the maximum tolerated dose (MTD) of OPB-111077 | • The highest dose that does not lead to discontinuation of dose escalation is defined as the MTD. | Within the first cycle [24 days] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) properties of OPB-111077 and its metabolites. | The following PK parameters (Cmax (maximum observed concentration), AUC(area uder the concentration time curve from zero), tmax (Time to maximum plasma concentration), etc.) will be determined using a non-compartmental methods. | Within the first cycle [24 days] | 
| Tumor response measured by RECIST(Response Evaluation Criteria in Solid Tumor) 1.1 | Assessment will be conducted at Screening, end of Cycle 1, end of Cycle 2, end of every 2 cycles thereafter, at the Early Termination (discontinuation) Visit. | Approximately 3-18 weeks depending on tumor response | 
| Biomarker of OPB-111077 | Change from baseline on predictable biomarker specified in the protocol | Within the first cycle [24 days] |