Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma
Brief summary
The purpose of this study is: Phase1: To evaluate the safety and determine the recommended dose (RD) Phase2: To evaluate the efficacy
Interventions
DRUGOPB-31121
Oral administration, 400 mg/day or 600 mg once daily after breakfast during the treatment period (1 month)
DRUGOPB-31121 phase2
Oral administration, recommended dose from Phase1 once daily after breakfast during the treatment period (6 months)
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Patients with histopathologically or clinically confirmed diagnosis of hepatocellular carcinoma * Patients with Child-Pugh classification A or B * Patients unresponsive to standard therapy or for whom standard therapy is intolerable, or for whom there is no appropriate therapy * Patients who are able to take oral medication * Patients age 20 to 79 years (inclusive) at time of informed consent * Patients with an ECOG performance status score of 0-2 * Patients have the eligible organ function.
Exclusion criteria
* Patients with a primary malignant tumor * Patients with a history of liver transplant * Patients with brain metastases * Patients with a complication of uncontrolled * Patients with a psychiatric disorder that might cause difficulty in obtaining informed consent or in conducting the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With Treatment Emergent Adverse Events | From first study medication to on Day 32 (after repeated 28 days medication from Day 4 to 32) | Treatment emergent adverse events observed during outcome measure time frame. |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | From first study medication to on Day 32 (after repeated 28 days medication from Day 4 to 32) | Recommended Dose (RD) of OPB-31121 was defined as the highest dose at which Dose Limited Toxicity (DLT) occurred at an incidence of \< 30%. DLT was defined as adverse events related to OPB-31121 occurring until Day 32, and 1) Grade 4 neutrophil count decreased persisting for ≧ 8 days, or Grade 3 or 4 febrile neutropenia, or infection with neutrophil count decreased 2) Grade 4 Plt decreased, or Grade 3 Plt decreased persisting for ≧ 8 days 3) Grade 3 or 4 nausea, vomiting, or diarrhoea that occurred despite the use of an anti-emetic or anti-diarrheal agents 4) Grade 3 or more severe AEsa excluding the AEs presented above 1) to 3) 5) AEs requiring interruption of IMP administration for a period of ≧ 8 consecutive days 6) Same AEs causing interruption of IMP administration twice |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | From first dose of study medication up to 28 weeks | Overall response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST guideline) - mRECIST 1.0. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPB-31121 OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 3 |
| Overall Study | Definite progression of primary disease | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | OPB-31121 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 64.0 years STANDARD_DEVIATION 7.3 |
| Region of Enrollment Japan | 23 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 4 / 4 | 7 / 7 | 5 / 5 |
| serious Total, serious adverse events | 0 / 7 | 0 / 4 | 0 / 7 | 2 / 5 |
Outcome results
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Recommended Dose (RD) of OPB-31121 was defined as the highest dose at which Dose Limited Toxicity (DLT) occurred at an incidence of \< 30%. DLT was defined as adverse events related to OPB-31121 occurring until Day 32, and 1) Grade 4 neutrophil count decreased persisting for ≧ 8 days, or Grade 3 or 4 febrile neutropenia, or infection with neutrophil count decreased 2) Grade 4 Plt decreased, or Grade 3 Plt decreased persisting for ≧ 8 days 3) Grade 3 or 4 nausea, vomiting, or diarrhoea that occurred despite the use of an anti-emetic or anti-diarrheal agents 4) Grade 3 or more severe AEsa excluding the AEs presented above 1) to 3) 5) AEs requiring interruption of IMP administration for a period of ≧ 8 consecutive days 6) Same AEs causing interruption of IMP administration twice
Time frame: From first study medication to on Day 32 (after repeated 28 days medication from Day 4 to 32)
Population: DLT evaluated subjects who had achieved ≧75% study drug compliance during a 4-week (28-day) treatment period starting from Day 4.~No statistical analysis provided for Subjects With DLTs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPB-31121 | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 participants |
| OPB-31121: 100 mg/Day | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 participants |
| OPB-31121: 200 mg/Day | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 participants |
| OPB-31121: 400 mg/Day | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 4 participants |
Primary
Subjects With Treatment Emergent Adverse Events
Treatment emergent adverse events observed during outcome measure time frame.
Time frame: From first study medication to on Day 32 (after repeated 28 days medication from Day 4 to 32)
Population: Safety population No statistical analysis provided for Subjects With Treatment Emergent Adverse Events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPB-31121 | Subjects With Treatment Emergent Adverse Events | 23 participants |
Secondary
Best Overall Response
Overall response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST guideline) - mRECIST 1.0.
Time frame: From first dose of study medication up to 28 weeks
Population: Efficacy population included all treated subjects who had received at least 1 dose of study drug.~No statistical analysis provided for Best Overall Responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OPB-31121 | Best Overall Response | CR or PR | 0 participants |
| OPB-31121 | Best Overall Response | SD ≧ 8w | 6 participants |
| OPB-31121 | Best Overall Response | PD | 9 participants |
| OPB-31121 | Best Overall Response | NE | 8 participants |