Safety and Biomarker of OPB-111077 in Subjects With Advanced Solid Tumor

Study Overview
=================
Brief Summary
-----------------
This open-label, non-randomized trial will comprise of 2 parts. A dose escalation part will characterize the safety, biomarker and pharmacokinetics of OPB-111077 in advanced solid tumor. Subsequently, an expansion part will further evaluate the biomarker, safety, pharmacokinetics and antitumor activity of OPB-111077 in selected tumor types.

Detailed Description
-----------------
This trial is designed to determine the safety, tolerability, maximum tolerated dose and recommended dose of OPB-111077 administered orally 4-days on and 3-days off (3 weeks/cycle) to subjects with advanced solid tumor in the dose escalation part so that biomarkers, efficacy, and others can be evaluated at the recommended dose in an expeditious manner in the expansion part. The dose escalation part employs a 3+3 escalation design as a standard dose escalation design for a small sample size.

Official Title
-----------------
A Phase 1, Open-label, Non-Randomized, Dose Escalation Trial to Evaluate Safety and Biomarker of OPB-111077 in Subjects With Advanced Solid Tumor

Conditions
-----------------
Solid Tumor

Intervention / Treatment
-----------------
* Drug: OPB-111077


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologically and/or cytologically confirmed advanced solid tumor Patients who were refractory to standard therapy or for which there are no standard treatment options available Age 20 to 80 years at the time of informed consent Patients who, together with their partner, are willing and capable of using an appropriate method of contraception throughout the trial period and until at least 12 weeks after final IMP administration Patients informed of the diagnosis of advanced solid tumor who are fully informed about the content of the study by the investigator or subinvestigator using the specified written consent form and other written explanation, and give written consent to participate in the study of their free will Patients who are able to take oral medication Exclusion Criteria: Patients with symptomatic brain metastases Patients who have not recovered from any prior therapy related toxicity deemed to be clinically significant at study entry, except for the test item defined in inclusion criteria. Patients with active infections needing whole body therapy Patients with positive hepatitis B surface (HBs) antigen or positive hepatitis C virus (HCV) antibody Patients with positive human immunodeficiency virus (HIV) antibody Patients with uncontrollable cardiac diseases Patients with uncontrollable pain by analgesic drugs Patients with a history of organ transplantation Patients who have received another IMP Patients who are pregnant, possibly pregnant, or lactating Patients otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPB-111077<br>Tablet, Oral, 300mg/500mg/700mg/900mg 4 days-on & 3 days-off (21 days=1cycle) | Drug: OPB-111077<br>* Tablet, Oral, 300mg/500mg/700mg/900mg 4 days-on & 3 days-off (21 days=1cycle)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants with Adverse Events | 21 days | 
| Maximum tolerated dose | The highest dose that does not lead to discontinuation of dose escalation | 21 days | 
| Biomarker of OPB-111077 | Change from baseline on predictable biomarker specified in the protocol | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response measured by RECIST(Response Evaluation Criteria in Solid Tumor) 1.1 Assessment | 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 final study visit. | 3 18 weeks depending on tumor response | 
| 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. | 21 days |