Liver Cancer
Conditions
Brief summary
This study will evaluate the efficacy and safety of oral Xeloda (capecitabine) plus intravenous Avastin (bevacizumab) in patients with advanced or metastatic liver cancer. The anticipated time on study treatment is 3-12 months.
Interventions
DRUGbevacizumab [Avastin]
7.5mg/kg iv on day 1 of each 3 week cycle.
DRUGcapecitabine [Xeloda]
1600mg/m2/day po in 2 divided doses, on days 1 to 14 of each 3 week cycle.
Sponsors
Hoffmann-La Roche
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
* adult patients \>=18 years of age; * advanced or metastatic liver cancer; * \>=1 measurable lesion.
Exclusion criteria
* current radiotherapy, chemotherapy, or other experimental therapies; * prior cytotoxic chemotherapy; * major surgery, open biopsy, or traumatic injury within 28 days of study entry; * history of a malignancy during the last 5 years, other than cutaneous basal cell cancer or in situ cervical cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. The best overall response achieved within the time from first drug administration to progressive disease or end of study was reported. CR was defined as complete disappearance of all target lesions and non-target disease, with the normalization of tumor marker levels. No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target lesions. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker levels above the normal limits. No new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression - Percentage of Participants With an Event | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of last tumor assessment. |
| Time to Disease Progression | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of their tumor assessment. |
| Time to Disease Progression - Percentage of Participants Progression-free at 12 Months | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. | Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of last tumor assessment. |
| Percentage of Participants With Disease Control | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | The percentage of participants with disease control was based on assessment of confirmed CR, PR, or stable disease (SD) according to RECIST criteria. Confirmed responses were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. The best overall response achieved within the time from first drug administration to progressive disease or end of study was reported. CR was defined as complete disappearance of all target lesions and non-target disease, with the normalization of tumor marker levels. No new lesions. PR was defined as ≥ 30 % decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target lesions. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker levels above the normal limits. No new lesions. SD was defined as not qualifying for PR or progressive disease. |
| Overall Survival | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. | Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive. Median Overall Survival was estimated using the Kaplan-Meier method. |
| Overall Survival - Percentage of Participants Event Free at 12 Months | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. | Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive. |
| Overall Survival - Percentage of Participants With an Event | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. | Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive. |
Countries
Australia, Hong Kong, Singapore, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab/Capecitabine A cycle was defined as the following: Participants received 7.5 mg/kg bevacizumab IV on Day 1 and 1600 mg/m\^2/day capecitabine, tablets, PO, in a divided dose every 12 hours starting the evening of Day 1 and ending on the morning of Day 15, followed by 1 week of no treatment. This cycle was repeated every 3 weeks until disease progression, development of unacceptable toxicity, or for a maximum of 6 cycles. If all 6 cycles were tolerated without disease progression or development of unacceptable toxicity, participants then could have repeated the cycle until disease progression. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 1 |
| Overall Study | Insufficient therapeutic response | 25 |
| Overall Study | Refused treatment | 1 |
Baseline characteristics
| Characteristic | Bevacizumab/Capecitabine |
|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 14.91 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 45 |
| serious Total, serious adverse events | 15 / 45 |
Outcome results
Primary
Percentage of Participants With Objective Response (OR)
Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. The best overall response achieved within the time from first drug administration to progressive disease or end of study was reported. CR was defined as complete disappearance of all target lesions and non-target disease, with the normalization of tumor marker levels. No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target lesions. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker levels above the normal limits. No new lesions.
Time frame: Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up
Population: Per Protocol (PP) Population included participants who: received greater than or equal to (≥) 1 dose of study medication, ≥6 weeks of treatment (unless excluded for allowed reasons), did not severely violate inclusion/exclusion criteria, had tumor assessment, greater than (\>) 50% of first 6 weeks of treatment, and were not replaced.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Capecitabine | Percentage of Participants With Objective Response (OR) | 9.1 percentage of participants |
Secondary
Overall Survival
Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive. Median Overall Survival was estimated using the Kaplan-Meier method.
Time frame: Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death.
Population: ITT Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Capecitabine | Overall Survival | 5.9 months |
Secondary
Overall Survival - Percentage of Participants Event Free at 12 Months
Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive.
Time frame: Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death.
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Capecitabine | Overall Survival - Percentage of Participants Event Free at 12 Months | 27 percentage of participants |
Secondary
Overall Survival - Percentage of Participants With an Event
Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive.
Time frame: Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death.
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Capecitabine | Overall Survival - Percentage of Participants With an Event | 77.8 percentage of participants |
Secondary
Percentage of Participants With Disease Control
The percentage of participants with disease control was based on assessment of confirmed CR, PR, or stable disease (SD) according to RECIST criteria. Confirmed responses were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. The best overall response achieved within the time from first drug administration to progressive disease or end of study was reported. CR was defined as complete disappearance of all target lesions and non-target disease, with the normalization of tumor marker levels. No new lesions. PR was defined as ≥ 30 % decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target lesions. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker levels above the normal limits. No new lesions. SD was defined as not qualifying for PR or progressive disease.
Time frame: Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up
Population: PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Capecitabine | Percentage of Participants With Disease Control | 52.3 percentage of participants |
Secondary
Time to Disease Progression
Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of their tumor assessment.
Time frame: Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up
Population: Intent-To-Treat (ITT) Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Capecitabine | Time to Disease Progression | 2.8 months |
Secondary
Time to Disease Progression - Percentage of Participants Progression-free at 12 Months
Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of last tumor assessment.
Time frame: Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death.
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Capecitabine | Time to Disease Progression - Percentage of Participants Progression-free at 12 Months | 24.0 percentage of participants |
Secondary
Time to Disease Progression - Percentage of Participants With an Event
Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of last tumor assessment.
Time frame: Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Capecitabine | Time to Disease Progression - Percentage of Participants With an Event | 77.8 percentage of participants |