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)

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: OPB-111077

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul & Gyeonggi-Do, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histopathologically or clinically diagnosed HCC by Korean Liver Cancer Study Group (KLCSG) guidelines.
2. Subject who has advanced HCC
3. Documented evidence of unresponsiveness to, intolerance to, or ineligibility for sorafenib, or unavailability of appropriate sorafenib treatment
4. Male or female subject, age at consent ≥20 years and ≤75 years.
5. Life expectancy ≥12 weeks.
6. 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.
7. 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:

1. Past liver transplantation
2. Uncontrollable hepatic encephalopathy or ascites
3. Presence of brain metastases
4. Clinically significant gastrointestinal bleeding in past 6 months or current active gastrointestinal bleeding.
5. Primary malignancy other than HCC
6. Human immunodeficiency virus (HIV) infection
7. Severe or poorly controlled complication that may affect the conduct or results of the study.
8. Use of Interferon preparation within 4 weeks (28 days) before start of study treatment in the present study.
9. Pregnant, nursing, or possibly pregnant women, or women desiring to become pregnant during the study period
10. Other cases judged by the Investigator to be ineligible for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPB-111077; orally, once daily	Drug: OPB-111077

What is the study measuring?

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]

Collaborators and Investigators

• Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): July 11, 2016

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: September 10, 2013
• First Posted (Estimate): September 13, 2013

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 7, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 317-12-001; There is no secondary ID.