Trial Outcomes & Findings for Phase 2 Study of TAC-101 Combined With Transcatheter Arterial Chemoembolization (TACE) Versus TACE Alone in Japanese Patients With Advanced Hepatocellular Carcinoma (NCT NCT00667628)

Last Updated: 2024-09-19

Results Overview

TTNL was defined as the time from the date of randomization to the date of appearance of a new lesion. Participants who had no appearance of new lesions had their TTNL censored at the date of their last tumor assessment.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE to date of appearance of a new lesion or until cut-off date (22-Dec-2009) (up to approximately 20 months)

Results posted on

2024-09-19

Participant Flow

A total of 67 participants were screened, of which 54 participants received the first transcatheter arterial chemoembolization (TACE) prior to randomization. Two participants discontinued prior to randomization due to adverse event and thus, a total of 52 participants were randomized in the study and received study drug in the double-blind period. The study was prematurely terminated by the Sponsor due to safety concerns.

Randomization was balanced between treatment arms according to the stratification factors of number of lesions (less than \[\<\] 5 versus greater than equal to \[\>=\] 5) and baseline alpha-fetoprotein (AFP) level (\<400 nanograms per milliliters \[ng/mL\] versus \>=400 ng/mL).

Participant milestones

Participant milestones
Measure	Placebo Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 Participants were administered with TAC-101 tablets, 20 milligrams per day (mg/day) orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.
Overall Study STARTED	25	27
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	25	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 Participants were administered with TAC-101 tablets, 20 milligrams per day (mg/day) orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.
Overall Study Lost to Follow-up	1	0
Overall Study Death	6	6
Overall Study Investigator Considers in Best Interest	1	0
Overall Study Sponsor Terminated Study	17	21

Baseline Characteristics

Phase 2 Study of TAC-101 Combined With Transcatheter Arterial Chemoembolization (TACE) Versus TACE Alone in Japanese Patients With Advanced Hepatocellular Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=25 Participants Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period. Repeated every 21 days cycle up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 n=27 Participants Participants were administered with TAC-101 tablets, 20 mg/day orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days cycle up to new lesions were observed or the participant met a treatment discontinuation criterion.	Total n=52 Participants Total of all reporting groups
Age, Continuous	68.6 years STANDARD_DEVIATION 9.77 • n=5 Participants	69.4 years STANDARD_DEVIATION 8.31 • n=7 Participants	69.1 years STANDARD_DEVIATION 8.96 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE to date of appearance of a new lesion or until cut-off date (22-Dec-2009) (up to approximately 20 months)

Population: Safety population included all participants who underwent a first combination with TACE procedure prior to randomization in this study, who were randomized and who received at least one dose of double-blind medication. Here, overall number of participants analyzed' signifies participants with available data for the outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 n=26 Participants Participants were administered with TAC-101 tablets, 20 mg/day orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.
Time to Appearance of New Lesions (TTNL)	8.4 months Standard Deviation 4.00	7.0 months Standard Deviation 4.07

SECONDARY outcome

Timeframe: From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE until cut-off date of 22 Dec 2009 (up to approximately 20 months)

OS was defined as the time from date of randomization to date of death. Participants who were still alive at the time of analysis had their survival time censored at the last date known to be alive.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 n=27 Participants Participants were administered with TAC-101 tablets, 20 mg/day orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.
Overall Survival (OS)	13.9 months Standard Deviation 2.87	13.2 months Standard Deviation 4.18

SECONDARY outcome

Timeframe: From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE until cut-off date of 22 Dec 2009 (up to approximately 20 months)

Population: The safety population was planned, with an independent review of tumor response. However, the independent reviews were deferred. Hence, the data was not collected and not evaluated.

PFS was defined as the time from date of randomization to the date of disease progression (radiological, only).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization (within 14 days prior to first TACE) assessed every 9 weeks after first TACE until cut-off date of 22 Dec 2009 (up to approximately 20 months)

Population: The safety population was planned, with an independent review of tumor response. However, the independent reviews were deferred. Hence, the data were not collected and not evaluated.

ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (\<)10 millimeters (mm). PR was defined as at least a 30 percent decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, End of treatment (last dose of study medication, i.e., approximately 7 months)

Population: Safety population included all participants who underwent a first combination with TACE procedure prior to randomization in this study, who were randomized and who received at least one dose of double-blind drug. Here, 'overall number of participants analyzed' signifies participants with available data for the outcome measure.

AFP was known as a tumor marker for advanced hepatocellular carcinoma (HCC) and was recognized as useful for following the course of HCC. Changes in serum AFP parallel the clinical course of HCC, where elevations can precede clinical deterioration and tumor recurrence.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 n=24 Participants Participants were administered with TAC-101 tablets, 20 mg/day orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.
Change From Baseline in Plasma Levels of Tumor Marker Alpha-fetoprotein (AFP)	-324.0 nanogram per milliliter (ng/mL) Standard Deviation 1903.05	8147.9 nanogram per milliliter (ng/mL) Standard Deviation 37555.15

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after last dose of study drug or until the start of new anti-tumor therapy, whichever was earlier (up to approximately 8.5 months)

Population: Safety population included all participants who had underwent a first combination with TACE procedure prior to randomization in this study, who were randomized and who had received at least one dose of double-blind medication.

Any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study drug was considered an adverse event (AE). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs: AEs that occur from the initiation of any study treatment administration, and do not necessarily have a causal relationship to the use of the study drug.

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 n=27 Participants Participants were administered with TAC-101 tablets, 20 mg/day orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	22 participants	25 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	2 participants	5 participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 22 other events

Deaths: 6 deaths

TAC-101

Serious events: 5 serious events

Other events: 25 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=25 participants at risk Participants were administered with placebo tablets matching to TAC-101 orally, every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) treatment recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.	TAC-101 n=27 participants at risk Participants were administered with TAC-101 tablets, 20 mg/day orally for every day on the first 14 days (Days 1 to 14) followed by a 7-day (Days 15 to 21) recovery period (21-day Cycle). Repeated every 21 days up to new lesions were observed or the participant met a treatment discontinuation criterion.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Gastrointestinal disorders Oesophageal varices haemorrhage	4.0% 1/25 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	0.00% 0/27 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
General disorders Disease progression	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Hepatobiliary disorders Cholecystitis	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Metabolism and nutrition disorders Anorexia	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Contralateral breast cancer	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Nervous system disorders Cerebral infarction	0.00% 0/25 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	3.7% 1/27 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.
Investigations Platelet count decreased	4.0% 1/25 • Number of events 1 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.	0.00% 0/27 • AEs were collected from first dose (i.e., Day 1) of study drug to last dose of study drug + 30 days (up to approximately 8.5 months). Deaths were collected from Baseline up to end of study (up to approximately 20 months). Reported AEs were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of study drug to the last dose of study drug + 30 days) and was assessed on safety population. All-Cause Mortality data collected during the study was assessed for all randomized participants.

Other adverse events

Additional Information

Taiho Central

Taiho Oncology, Inc.

Phone: +1 844-878-2446

Email: [email protected]

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Principal investigator is a sponsor employee
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