Phase I/II Study of OPB-31121 in Patients With Progressive Hepatocellular Carcinoma

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01406574
• Collaborator: (none)
• Enrollment: 23
• Locations: 2
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 11.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is:

Phase1: To evaluate the safety and determine the recommended dose (RD) Phase2: To evaluate the efficacy

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: OPB-31121; Drug: OPB-31121 phase2	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Non-randomized, Dose-escalation, Therapeutic Exploratory Trial to Evaluate the Safety and Efficacy of OPB-31121 in Patients With Progressive Hepatocellular Carcinoma
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OPB-31121 p1 Phase1 step	Drug: OPB-31121; Oral administration, 400 mg/day or 600 mg once daily after breakfast during the treatment period (1 month)
Experimental: OPB-31121 p2 Phase2 step	Drug: OPB-31121 phase2; Oral administration, recommended dose from Phase1 once daily after breakfast during the treatment period (6 months)

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chiba		Japan
2		Tokyo		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01406574
• Other Study ID Numbers: 252-11-001; JapicCTI-111546
• First Posted: Aug 1, 2011
• Last Update Posted: Jun 8, 2015
• Last Verified: May 1, 2015

• Keywords provided by Otsuka Pharmaceutical Co., Ltd.: Hepatocellular carcinoma
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

Participant Flow

Arm/Group Title	OPB-31121: 50mg/Day	OPB-31121: 100mg/Day	OPB-31121: 200mg/Day	OPB-31121: 400mg/Day
Arm/Group Description	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle
Period Title: Overall Study
STARTED	7	4	7	5
COMPLETED	6	3	6	1
NOT COMPLETED	1	1	1	4

Baseline Characteristics

Arm/Group Title	OPB-31121
Arm/Group Description	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.
Overall Participants	23
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 47.8%
>=65 years	12 52.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (7.3)
Sex: Female, Male (Count of Participants)
Female	3 13%
Male	20 87%
Region of Enrollment (participants) [Number]
Japan	23 100%

Outcome Measures

1. Primary Outcome

Title	Subjects With Treatment Emergent Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

Safety population No statistical analysis provided for Subjects With Treatment Emergent Adverse Events.

Arm/Group Title	OPB-31121
Arm/Group Description	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.
Measure Participants	23
Number [participants]	23 100%

2. Primary Outcome

Title	Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	OPB-31121: 50 mg/Day	OPB-31121: 100 mg/Day	OPB-31121: 200 mg/Day	OPB-31121: 400 mg/Day
Arm/Group Description	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle
Measure Participants	7	4	7	5
Number [participants]	0 0%	0 NaN	1 NaN	4 NaN

3. Secondary Outcome

Title	Best Overall Response
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	OPB-31121
Arm/Group Description	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.
Measure Participants	23
CR or PR	0 0%
SD ≧ 8w	6 26.1%
PD	9 39.1%
NE	8 34.8%

Adverse Events

Time Frame	From first study medication to end-of-trial examination
Arm/Group Title	OPB-31121: 50 mg/Day		OPB-31121: 100 mg/Day		OPB-31121: 200 mg/Day		OPB-31121: 400 mg/Day
Arm/Group Description	OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.		OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.		OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.		OPB-31121: 50, 100, 200 and 400 mg/day oral once daily (QD) in a 4 week cycle.
All Cause Mortality
	OPB-31121: 50 mg/Day		OPB-31121: 100 mg/Day		OPB-31121: 200 mg/Day		OPB-31121: 400 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	OPB-31121: 50 mg/Day		OPB-31121: 100 mg/Day		OPB-31121: 200 mg/Day		OPB-31121: 400 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/4 (0%)		0/7 (0%)		2/5 (40%)
General disorders
Gait disturbance	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/5 (20%)	1
Hepatobiliary disorders
Jaundice	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/5 (20%)	1
Nervous system disorders
Peripheral sensory neuropathy	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	OPB-31121: 50 mg/Day		OPB-31121: 100 mg/Day		OPB-31121: 200 mg/Day		OPB-31121: 400 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		4/4 (100%)		7/7 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Leukopenia	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	3/5 (60%)	3
Gastrointestinal disorders
Nausea	4/7 (57.1%)	4	4/4 (100%)	4	7/7 (100%)	7	5/5 (100%)	5
Vomiting	4/7 (57.1%)	4	3/4 (75%)	3	7/7 (100%)	7	5/5 (100%)	5
Diarrhea	2/7 (28.6%)	2	4/4 (100%)	4	6/7 (85.7%)	6	4/5 (80%)	4
Fatigue/malaise	5/7 (71.4%)	5	1/4 (25%)	1	4/7 (57.1%)	4	2/5 (40%)	2
Investigations
Neutrophil count decreased	1/7 (14.3%)	1	1/4 (25%)	1	1/7 (14.3%)	1	0/5 (0%)	0
Platelet count decreased	1/7 (14.3%)	1	1/4 (25%)	1	1/7 (14.3%)	1	0/5 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/7 (14.3%)	1	2/4 (50%)	2	3/7 (42.9%)	3	5/5 (100%)	5
Nervous system disorders
Peripheral sensory neuropathy	0/7 (0%)	0	0/4 (0%)	0	4/7 (57.1%)	4	2/5 (40%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.