Carcinoma, Hepatocellular
Conditions
Keywords
HCC, Cancer, Liver Cancer, TACE
Brief summary
Clinical trial of BAY43-9006 in patients with hepatocellular carcinoma.
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Multikinase Inhibitor; Sorafenib: 400mg bid of sorafenib
DRUGPlacebo
Placebo: matching placebo
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female * Aged of 18 and over * Advanced hepatocellular carcinoma
Exclusion criteria
* History of prior systemic chemotherapy * Failure in vital organ
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | From randomization of the first subject until radiological progression or recurrence whichever came first, assessed up to 39 months. | Time to progression (TTP) was defined as the time from date of randomization to radiological progression / recurrence. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization of the first subject until 39 months later. | Overall survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at their last date of follow-up were censored at the time of analysis. |
Countries
Japan, South Korea
Participant flow
Recruitment details
The first subject was enrolled on 27 Aug 2006. The final data collection date for the primary endpoint analysis was 10 Jul 2009. The study was conducted at 77 centers from 2 countries: Korea (7 centers) and Japan (70). 76 centers enrolled at least 1 subject (7 centers in Korea and 69 in Japan). The last subject's last visit occurred on 19 Nov 2010.
Pre-assignment details
Of 552 subjects screened, 458 were randomized and were valid for the efficacy analyses (intent to treat \[ITT\] population), and 456 received at least 1 dose of study drug and were valid for the safety analyses. 229 subjects were randomized to each group (sorafenib or placebo).
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) Sorafenib (Nexavar, BAY43-9006) administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid) (morning and evening, every 12 hours as far as possible); Dose modification (delayed or reduced) was permitted due to toxicity. | 229 |
| Placebo Sorafenib (Nexavar, BAY43-9006) matching placebo (2 placebo tablets) orally administered bid (twice daily). | 229 |
| Total | 458 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 93 | 13 |
| Overall Study | Disease Progression, Recurrence/Relapse | 109 | 185 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Participant Did Not Take Study Drug | 0 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Driven Decision Point | 11 | 22 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Site Closed by Sponsor | 6 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Sorafenib (Nexavar, BAY43-9006) |
|---|---|---|---|
| Age, Continuous | 68.1 Years STANDARD_DEVIATION 8.8 | 67.8 Years STANDARD_DEVIATION 8.7 | 67.5 Years STANDARD_DEVIATION 8.7 |
| Child Pugh Status Status A | 229 Participants | 458 Participants | 229 Participants |
| Child Pugh Status Status B | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 | 202 Participants | 403 Participants | 201 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 1 | 27 Participants | 55 Participants | 28 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 2 | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 3 | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Grade 4 | 0 Participants | 0 Participants | 0 Participants |
| Number of Prior transcatheter arterial chemoembolization (TACE) 1 | 148 Participants | 295 Participants | 147 Participants |
| Number of Prior transcatheter arterial chemoembolization (TACE) 2 | 81 Participants | 163 Participants | 82 Participants |
| Responder group to transcatheter arterial chemoembolization (TACE) Responder Group A | 142 Participants | 284 Participants | 142 Participants |
| Responder group to transcatheter arterial chemoembolization (TACE) Responder Group B | 87 Participants | 174 Participants | 87 Participants |
| Sex: Female, Male Female | 61 Participants | 116 Participants | 55 Participants |
| Sex: Female, Male Male | 168 Participants | 342 Participants | 174 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 229 / 229 | 193 / 227 |
| serious Total, serious adverse events | 44 / 229 | 21 / 227 |
Outcome results
Primary
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from date of randomization to radiological progression / recurrence. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation.
Time frame: From randomization of the first subject until radiological progression or recurrence whichever came first, assessed up to 39 months.
Population: Intention to treat (ITT) population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Time to Progression (TTP) | 164 days |
| Placebo | Time to Progression (TTP) | 112 days |
95% CI: [0.6972, 1.0942]
Secondary
Overall Survival (OS)
Overall survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at their last date of follow-up were censored at the time of analysis.
Time frame: From randomization of the first subject until 39 months later.
Population: Median overall survival (OS) and 95% Confidence interval (CI) were not estimable in Placebo Group and Upper Limit of 95% CI was not in Sorafenib Group because of more than half (188 for Placebo,186 for Sorafenib) of the individual study populations censored. Number of death is shown in Post-Hoc Outcome Measure.
Post Hoc
Number of Death Cases Due to Any Cause
Time frame: From randomization of the first subject until death due to any cause assessed up to 55 months.
Population: Intention to treat (ITT) population. Overall Survival is shown in Secondary Outcome Measure: Overall Survival.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Number of Death Cases Due to Any Cause | up to 39 months | 43 Participants |
| Sorafenib (Nexavar, BAY43-9006) | Number of Death Cases Due to Any Cause | up to 55 months | 50 Participants |
| Placebo | Number of Death Cases Due to Any Cause | up to 39 months | 41 Participants |
| Placebo | Number of Death Cases Due to Any Cause | up to 55 months | 56 Participants |