Carcinoma, Hepatocellular
Conditions
Keywords
Cancer, Liver Cancer, Hepatocellular carcinoma (HCC)
Brief summary
Evaluate anti-cancer activity (e.g. proportion of patients with confirmed complete response or partial response) in patients with advanced, inoperable biopsy-proven hepatocellular carcinoma.
Detailed description
In addition to the key secondary outcome parameters the following exploratory parameters were evaluated in subpopulations: * Pharmacokinetics (PK) profile of Sorafenib * Plasma and tissue tumor biomarkers
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Sorafenib (Nexavar, BAY43-9006) 400 mg administered bis in die (bid, twice a day)
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed primary hepatocellular carcinoma (HCC) * Inoperable disease (T2-T4, any N, M0 or M1) or refused surgery * Measurable disease * At least 1 bidimensionally measurable lesion of at least 2 cm by computed tomography (CT) scan or magnetic resonance imaging (MRI) * Presence of at least 1 of the following: * Alpha-fetoprotein greater than the upper limit of normal (ULN) * Hepatitis C antibody positive * Hepatitis B surface antigen positive * Child's Pugh class A or B * Candidate for systemic therapy
Exclusion criteria
* Fibrolamellar disease mixed histology * Metastatic brain or meningeal tumors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants for Each Type of Response | Until 30 days after termination of active therapy | Objective response rate of sorafenib assessed as the proportion of subjects with confirmed complete or partial response as per modified World Health Organization (WHO) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Start of treatment to death | Time from the first date of receiving study medication to death. |
| Duration of Response | up to 3 years later | Duration of response was calculated from the first drug treatment date until documented progressive disease (PD). PD was 1) 25% or more increase in the sum of all target lesion areas taking as reference the smallest sum recorded at or following baseline, 2) unequivocal progression of an existing non-target lesion, or 3) appearance of a new lesion. |
| Time to Response | up to 3 years later | Time from the first day of receiving study drug to the date the CR or PR was documented (with confirmation). |
| Duration of Minor Response | Time from MR to PD | Time from the date that MR was first documented to the date that PD was first documented. |
| Duration of Stable Disease | up to 3 years later | Time from the first day of receiving study drug until there was a documented PD or response. |
| Time to Minor Response | up to 3 years later | Time from the first day of receiving study drug to the date the MR was first documented (with confirmation). Minor response = \>25% regression. |
| Time to Progression | up to 3 years later | Time from the first date of receiving study drug until the first documented PD. |
Countries
Belgium, France, Israel, Italy, United States
Participant flow
Recruitment details
Only subjects with measurable, histologically or cytologically documented hepatocellur carcinoma (HCC) which was inoperable or who had refused surgery could participate in this study.
Pre-assignment details
Of 147 enrolled patients, 137 received treatment. 10 patients failed screening; reasons were: target lesions identified at baseline (3), liver function tests too high for inclusion (2), prior systemic anticancer treatment (2), creatinine too high for inclusion (1), platelets too low for inclusion (1), diagnosis of HCC not confirmed (1)
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib 400 mg b.i.d. Sorafenib (Nexavar, BAY43-9006) 400 mg administered bis in die (bid, twice a day) | 137 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow Up | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Sorafenib 400 mg b.i.d. |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 53 Participants |
| Age, Categorical Between 18 and 65 years | 84 Participants |
| Child Pugh Status Missing | 1 participants |
| Child Pugh Status Status A | 98 participants |
| Child Pugh Status Status B | 38 participants |
| Eastern Cooperative Group performance status (ECOG PS) at study entry Grade 0 | 68 participants |
| Eastern Cooperative Group performance status (ECOG PS) at study entry Grade 1 | 69 participants |
| Eastern Cooperative Group performance status (ECOG PS) at study entry Grade 2 | 0 participants |
| Eastern Cooperative Group performance status (ECOG PS) at study entry Grade 3 | 0 participants |
| Eastern Cooperative Group performance status (ECOG PS) at study entry Grade 4 | 0 participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 97 Participants |
| Stage of Disease at study entry (TNM Classification) Stage 1 | 0 participants |
| Stage of Disease at study entry (TNM Classification) Stage 2 | 4 participants |
| Stage of Disease at study entry (TNM Classification) Stage 3 | 42 participants |
| Stage of Disease at study entry (TNM Classification) Stage 4 | 91 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 126 / 137 |
| serious Total, serious adverse events | 77 / 137 |
Outcome results
Primary
Percentage of Participants for Each Type of Response
Objective response rate of sorafenib assessed as the proportion of subjects with confirmed complete or partial response as per modified World Health Organization (WHO) criteria.
Time frame: Until 30 days after termination of active therapy
Population: Intention to Treat (ITT) analyses were performed on subgroups of patients categorized by baseline characteristics of ECOG Performance Status, Child Pugh status, TNM stage at study entry, prior surgical procedure, hepatitis A and B status, and age.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib 400 mg b.i.d. | Percentage of Participants for Each Type of Response | Complete response (CR) | 0 percentage of participants |
| Sorafenib 400 mg b.i.d. | Percentage of Participants for Each Type of Response | Partial response (PR) | 2.2 percentage of participants |
| Sorafenib 400 mg b.i.d. | Percentage of Participants for Each Type of Response | Minor response (MR) | 5.8 percentage of participants |
| Sorafenib 400 mg b.i.d. | Percentage of Participants for Each Type of Response | Stable disease (SD) | 54.7 percentage of participants |
| Sorafenib 400 mg b.i.d. | Percentage of Participants for Each Type of Response | Progressive disease (PD) | 13.9 percentage of participants |
| Sorafenib 400 mg b.i.d. | Percentage of Participants for Each Type of Response | Not available for independent review (NA) | 22.6 percentage of participants |
| Sorafenib 400 mg b.i.d. | Percentage of Participants for Each Type of Response | Not evaluable (NE) | 0.7 percentage of participants |
Secondary
Duration of Minor Response
Time from the date that MR was first documented to the date that PD was first documented.
Time frame: Time from MR to PD
Population: Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sorafenib 400 mg b.i.d. | Duration of Minor Response | 122 days |
Secondary
Duration of Response
Duration of response was calculated from the first drug treatment date until documented progressive disease (PD). PD was 1) 25% or more increase in the sum of all target lesion areas taking as reference the smallest sum recorded at or following baseline, 2) unequivocal progression of an existing non-target lesion, or 3) appearance of a new lesion.
Time frame: up to 3 years later
Population: Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and C status (positive vs negative). The 3 subjects are censored at time of evaluation. The Median is not estimable so the reported number is biased.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib 400 mg b.i.d. | Duration of Response | 374 days |
Secondary
Duration of Stable Disease
Time from the first day of receiving study drug until there was a documented PD or response.
Time frame: up to 3 years later
Population: Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib 400 mg b.i.d. | Duration of Stable Disease | 166 days |
Secondary
Overall Survival
Time from the first date of receiving study medication to death.
Time frame: Start of treatment to death
Population: Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib 400 mg b.i.d. | Overall Survival | 280 days |
Secondary
Time to Minor Response
Time from the first day of receiving study drug to the date the MR was first documented (with confirmation). Minor response = \>25% regression.
Time frame: up to 3 years later
Population: Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib 400 mg b.i.d. | Time to Minor Response | 84 days |
Secondary
Time to Progression
Time from the first date of receiving study drug until the first documented PD.
Time frame: up to 3 years later
Population: Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib 400 mg b.i.d. | Time to Progression | 167 days |
Secondary
Time to Response
Time from the first day of receiving study drug to the date the CR or PR was documented (with confirmation).
Time frame: up to 3 years later
Population: Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib 400 mg b.i.d. | Time to Response | 144 days |