Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) and Transarterial Chemoembolisation (TACE) Treatment in Patients With Liver Cancer (NCT NCT00576199)
NCT ID: NCT00576199
Last Updated: 2014-08-29
Results Overview
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.
COMPLETED
PHASE2
30 participants
Baseline to the end of the study (up to 3 years, 3 months)
2014-08-29
Participant Flow
The Participant Flow data are discontinuations from bevacizumab treatment. Data for discontinuations from the study are not available.
Participant milestones
| Measure |
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.
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|---|---|
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Overall Study
STARTED
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30
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Overall Study
COMPLETED
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0
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Overall Study
NOT COMPLETED
|
30
|
Reasons for withdrawal
| Measure |
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.
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|---|---|
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Overall Study
Adverse Event
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12
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Overall Study
Insufficient Therapeutic Response
|
14
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Overall Study
Refused Treatment
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2
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Overall Study
Reason Unspecified
|
2
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Baseline Characteristics
A Study of Avastin (Bevacizumab) and Transarterial Chemoembolisation (TACE) Treatment in Patients With Liver Cancer
Baseline characteristics by cohort
| Measure |
Bevacizumab 5 mg/kg
n=30 Participants
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.
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|---|---|
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Age, Continuous
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62.8 years
STANDARD_DEVIATION 10.43 • n=39 Participants
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Sex: Female, Male
Female
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4 Participants
n=39 Participants
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Sex: Female, Male
Male
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26 Participants
n=39 Participants
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PRIMARY outcome
Timeframe: Baseline to the end of the study (up to 3 years, 3 months)Population: Intent-to-treat population: All participants who received study medication.
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.
Outcome measures
| Measure |
Bevacizumab 5 mg/kg
n=30 Participants
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.
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|---|---|
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Progression-free Survival
|
11.6 Months
Interval 6.3 to 15.7
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SECONDARY outcome
Timeframe: Baseline to the end of the study (up to 3 years, 3 months)Population: Intent-to-treat population: All participants who received study medication.
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.
Outcome measures
| Measure |
Bevacizumab 5 mg/kg
n=30 Participants
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.
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|---|---|
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Percentage of Participants With an Objective Response
|
23.3 Percentage of participants
Interval 9.9 to 42.3
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SECONDARY outcome
Timeframe: Baseline to the end of the study (up to 3 years, 3 months)Population: Intent-to-treat population: All participants who received study medication.
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.
Outcome measures
| Measure |
Bevacizumab 5 mg/kg
n=30 Participants
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.
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|---|---|
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Time to Progression
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12.0 Months
Interval 6.3 to 17.1
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SECONDARY outcome
Timeframe: Baseline to the end of the study (up to 3 years, 3 months)Population: Intent-to-treat population: All participants who received study medication.
Overall survival was defined as the time from the first administration of study drug to death.
Outcome measures
| Measure |
Bevacizumab 5 mg/kg
n=30 Participants
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.
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|---|---|
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Overall Survival
|
19.9 Months
Interval 10.3 to 27.6
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SECONDARY outcome
Timeframe: Baseline to the end of the study (up to 3 years, 3 months)Population: Intent-to-treat population: All participants who received study medication.
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.
Outcome measures
| Measure |
Bevacizumab 5 mg/kg
n=30 Participants
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.
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|---|---|
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Percentage of Participants With a Best Overall Response of Complete Response, Partial Response, or Stable Disease
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86.7 Percentage of participants
Interval 69.3 to 96.2
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SECONDARY outcome
Timeframe: Baseline to the end of the study (up to 3 years, 3 months)Population: Intent-to-treat population: All participants who received study medication.
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.
Outcome measures
| Measure |
Bevacizumab 5 mg/kg
n=30 Participants
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.
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|---|---|
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Tumor Necrosis
Lesion 1 (N= 29)
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1.3 Percentage of tumor volume at Baseline
Standard Deviation 1.00
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Tumor Necrosis
Lesion 2 (N= 11)
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0.8 Percentage of tumor volume at Baseline
Standard Deviation 0.87
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Tumor Necrosis
Lesion 3 (N= 5)
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1.6 Percentage of tumor volume at Baseline
Standard Deviation 1.14
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Tumor Necrosis
Lesion 4 (N= 5)
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1.2 Percentage of tumor volume at Baseline
Standard Deviation 1.30
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Tumor Necrosis
Lesion 5 (N= 4)
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1.0 Percentage of tumor volume at Baseline
Standard Deviation 1.41
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Adverse Events
Bevacizumab 5 mg/kg
Serious adverse events
| Measure |
Bevacizumab 5 mg/kg
n=30 participants at risk
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.
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|---|---|
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Gastrointestinal disorders
Abdominal pain upper
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6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Gastrointestinal disorders
Abdominal pain
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Gastrointestinal disorders
Duodenal ulcer
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Gastrointestinal disorders
Haemorrhoidal haemorrhage
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Gastrointestinal disorders
Haemorrhoids
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Gastrointestinal disorders
Oesophageal perforation
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Gastrointestinal disorders
Oesophageal varices haemorrhage
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Gastrointestinal disorders
Pancreatitis acute
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Infections and infestations
Liver abscess
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6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Infections and infestations
Gastroenteritis
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Infections and infestations
Pneumonia
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Infections and infestations
Pulmonary tuberculosis
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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General disorders
Chest discomfort
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6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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General disorders
Pyrexia
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6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Respiratory, thoracic and mediastinal disorders
Dyspnoea
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Respiratory, thoracic and mediastinal disorders
Epistaxis
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Respiratory, thoracic and mediastinal disorders
Pleural effusion
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Hepatobiliary disorders
Cholangitis
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Hepatobiliary disorders
Hepatic cirrhosis
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liver carcinoma ruptured
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6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Vascular disorders
Hypertension
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6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Cardiac disorders
Bradycardia
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Cardiac disorders
Cardiac failure
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Blood and lymphatic system disorders
Thrombocytopenia
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Ear and labyrinth disorders
Vertigo
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Injury, poisoning and procedural complications
Vascular pseudoaneurysm
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Musculoskeletal and connective tissue disorders
Back pain
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Renal and urinary disorders
Urinary retention
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3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Other adverse events
| Measure |
Bevacizumab 5 mg/kg
n=30 participants at risk
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.
|
|---|---|
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Vascular disorders
Hypertension
|
33.3%
10/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Epistaxis
|
6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Gingival bleeding
|
6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Injection site haematoma
|
6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Puncture site haemorrhage
|
6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Haemoptysis
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Haemorrhoidal haemorrhage
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Oesophageal varices
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Haemorrhage
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
13.3%
4/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Hepatobiliary disorders
Liver abscess
|
6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Blood and lymphatic system disorders
Hyperbilirubinaemia
|
6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Wound complication
|
6.7%
2/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Atrial fibrillation
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Cardiac failure
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Oesophageal perforation
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Renal and urinary disorders
Proteinuria
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
|
|
Vascular disorders
Portal vein thrombosis
|
3.3%
1/30 • Adverse events were reported from enrollment in the study up to 28 days after treatment completion.
Safety population: All participants who received at least 1 dose of study medication.
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Additional Information
Medical Communications
Hoffmann-La Roche
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER