Liver Cancer
Conditions
Brief summary
This single-arm, open-label study assessed the efficacy and safety of Avastin (bevacizumab) treatment combined with transarterial chemoembolisation (TACE) in patients with localized unresectable liver cancer. Patients were treated with TACE at 8 or 10 week intervals for 4 sessions (continuation depended on investigator's discretion). Avastin 5 mg/kg intravenously was administered 24-48 hours prior to each TACE session and every 2 weeks between the TACE sessions until disease progression.
Interventions
DRUGBevacizumab
Bevacizumab was supplied as a sterile liquid in single-use vials.
TACE was conducted by the transfemoral artery approach with selective cannulation of the artery supplying the tumor. Cisplatin mixed with Lipiodol in a 1 mg:1 mL ratio was infused intra-arterially up to a maximum dose of 30 mg, depending on tumor size, followed by embolization of the artery using Gelfoam particle until the blood flow slowed. Bilobar lesions were treated by separate catheterization of right and left hepatic arteries followed by injection of the cisplatin-Lipiodol mixture and embolization. Patients with stable disease or a partial response after 4 TACE sessions could be given further TACEs upon the investigator's discretion until there was evidence of progressive disease or contraindication due to severe complication or technical failure to perform the TACE.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
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. * Liver cancer, not suitable for resection. * At least 1 measurable lesion, and overall tumor lesions occupying \< 50% of liver volume * Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Exclusion criteria
* Patients receiving concurrent radiotherapy or immunotherapy. * Patients who have received previous chemotherapy, biological agents, or radiotherapy. * Prior transarterial chemoembolisation (TACE) or transarterial embolisation (TAE). * Prior liver transplantation or liver resection. * Current or recent (within 10 days of study start) use of full-dose anticoagulants for therapeutic purposes. * Patients with high risk esophageal/gastric varices.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Baseline to the end of the study (up to 3 years, 3 months) | Progression-free survival was defined as the time from the first administration of study drug to the first documented disease progression or death, whichever occurs first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Objective Response | Baseline to the end of the study (up to 3 years, 3 months) | An objective response was defined as a complete response or a partial response. A complete response was defined as the disappearance of all target lesions. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the Baseline sum longest diameter. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter. |
| Time to Progression | Baseline to the end of the study (up to 3 years, 3 months) | Time to progression was defined as the time from the first administration of study drug to the first documented disease progression. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter. |
| Overall Survival | Baseline to the end of the study (up to 3 years, 3 months) | Overall survival was defined as the time from the first administration of study drug to death. |
| Percentage of Participants With a Best Overall Response of Complete Response, Partial Response, or Stable Disease | Baseline to the end of the study (up to 3 years, 3 months) | A complete response was defined as the disappearance of all target lesions. A partial response was defined as at least a 30% decrease in the sum of the LD of target lesions taking as reference the Baseline sum LD. Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the LD) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the LD for all target lesions will be calculated and reported as the Baseline sum LD. |
| Tumor Necrosis | Baseline to the end of the study (up to 3 years, 3 months) | Tumor necrosis was quantified in liver lesions greater than 2 cm at Baseline. When MRI showed many cut surfaces for a single tumor, tumor size and the size of necrotic area was measured by accumulation of the serial sections containing the tumor. Lipiodol accumulation in tumor after TACE was regarded as an indication of necrosis. Tumor necrosis was assessed at Baseline and 1 week prior to the next scheduled transarterial chemoembolisation (TACE) for the first 4 TACEs, then 1 week prior to every second TACE till disease progression. The extent of tumor necrosis is presented as the percentage of the tumor volume at Baseline. |
Countries
Hong Kong
Participant flow
Pre-assignment details
The Participant Flow data are discontinuations from bevacizumab treatment. Data for discontinuations from the study are not available.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab 5 mg/kg Participants received bevacizumab 5 mg/kg intravenously every 2 weeks and within 24-48 hours prior to each transarterial chemoembolization (TACE) until disease progression or unmanageable toxicity. TACE was conducted for 4 sessions at 8-10 week intervals. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Insufficient Therapeutic Response | 14 |
| Overall Study | Reason Unspecified | 2 |
| Overall Study | Refused Treatment | 2 |
Baseline characteristics
| Characteristic | Bevacizumab 5 mg/kg |
|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 10.43 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 30 |
| serious Total, serious adverse events | 17 / 30 |
Outcome results
Primary
Progression-free Survival
Progression-free survival was defined as the time from the first administration of study drug to the first documented disease progression or death, whichever occurs first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter.
Time frame: Baseline to the end of the study (up to 3 years, 3 months)
Population: Intent-to-treat population: All participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab 5 mg/kg | Progression-free Survival | 11.6 Months |
Secondary
Overall Survival
Overall survival was defined as the time from the first administration of study drug to death.
Time frame: Baseline to the end of the study (up to 3 years, 3 months)
Population: Intent-to-treat population: All participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab 5 mg/kg | Overall Survival | 19.9 Months |
Secondary
Percentage of Participants With a Best Overall Response of Complete Response, Partial Response, or Stable Disease
A complete response was defined as the disappearance of all target lesions. A partial response was defined as at least a 30% decrease in the sum of the LD of target lesions taking as reference the Baseline sum LD. Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the LD) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the LD for all target lesions will be calculated and reported as the Baseline sum LD.
Time frame: Baseline to the end of the study (up to 3 years, 3 months)
Population: Intent-to-treat population: All participants who received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab 5 mg/kg | Percentage of Participants With a Best Overall Response of Complete Response, Partial Response, or Stable Disease | 86.7 Percentage of participants |
Secondary
Percentage of Participants With an Objective Response
An objective response was defined as a complete response or a partial response. A complete response was defined as the disappearance of all target lesions. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the Baseline sum longest diameter. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter.
Time frame: Baseline to the end of the study (up to 3 years, 3 months)
Population: Intent-to-treat population: All participants who received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab 5 mg/kg | Percentage of Participants With an Objective Response | 23.3 Percentage of participants |
Secondary
Time to Progression
Time to progression was defined as the time from the first administration of study drug to the first documented disease progression. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter.
Time frame: Baseline to the end of the study (up to 3 years, 3 months)
Population: Intent-to-treat population: All participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab 5 mg/kg | Time to Progression | 12.0 Months |
Secondary
Tumor Necrosis
Tumor necrosis was quantified in liver lesions greater than 2 cm at Baseline. When MRI showed many cut surfaces for a single tumor, tumor size and the size of necrotic area was measured by accumulation of the serial sections containing the tumor. Lipiodol accumulation in tumor after TACE was regarded as an indication of necrosis. Tumor necrosis was assessed at Baseline and 1 week prior to the next scheduled transarterial chemoembolisation (TACE) for the first 4 TACEs, then 1 week prior to every second TACE till disease progression. The extent of tumor necrosis is presented as the percentage of the tumor volume at Baseline.
Time frame: Baseline to the end of the study (up to 3 years, 3 months)
Population: Intent-to-treat population: All participants who received study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab 5 mg/kg | Tumor Necrosis | Lesion 1 (N= 29) | 1.3 Percentage of tumor volume at Baseline | Standard Deviation 1 |
| Bevacizumab 5 mg/kg | Tumor Necrosis | Lesion 2 (N= 11) | 0.8 Percentage of tumor volume at Baseline | Standard Deviation 0.87 |
| Bevacizumab 5 mg/kg | Tumor Necrosis | Lesion 3 (N= 5) | 1.6 Percentage of tumor volume at Baseline | Standard Deviation 1.14 |
| Bevacizumab 5 mg/kg | Tumor Necrosis | Lesion 4 (N= 5) | 1.2 Percentage of tumor volume at Baseline | Standard Deviation 1.3 |
| Bevacizumab 5 mg/kg | Tumor Necrosis | Lesion 5 (N= 4) | 1.0 Percentage of tumor volume at Baseline | Standard Deviation 1.41 |