Liver Cancer
Conditions
Brief summary
This single arm study evaluated the efficacy and safety of a combination of Tarceva and Avastin in patients with advanced or metastatic liver cancer. Patients were treated with Tarceva 150 mg po daily plus Avastin 5 mg/kg intravenous (iv) every 2 weeks. The anticipated time on study treatment was until disease progression, and the target sample size was \<100 individuals.
Interventions
DRUGbevacizumab (Avastin)
5 mg/kg iv on day 1 of each 2 week cycle.
150 mg orally (po) daily.
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, not previously treated with local therapy within 4 weeks of enrollment.
Exclusion criteria
* prior or concomitant systemic anti-cancer treatment for advanced disease; * patients at high risk of variceal bleeding; * clinically significant cardiovascular disease; * major surgery, open biopsy, or significant traumatic injury within 4 weeks of study start.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Progression-free Survival (PFS) | Week 16 | Percentage of participants who were alive and without documented progressive disease 16 weeks after their first dose of study drug. Diagnosis of Progressive Disease was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Event driven (median follow-up 12 months) | Disease Control Rate was defined as the percentage of participants with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at least 8 weeks by Response Evaluation Criteria in Solid Tumours (RECIST). CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; for non-target lesions persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits. |
| Time to Tumor Progression | Event driven (median follow-up 12 months) | Time to tumor progression was defined as the time period in months from the start of study drug treatment to disease progression. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Overall Response Rate (ORR) | Event driven (median follow-up 12 months) | ORR was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR). Analysis of tumor response was based on the best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST), which was defined as the best response recorded from the start of trial treatment until disease progression/recurrence (or death), taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. PD required at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Overall Survival (OS) | Event driven (median follow-up 12 months) | OS was defined as the time period in months from the start of study drug treatment to death. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 107 Weeks | An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. |
| Progression-free Survival (PFS) | Event driven (median follow-up 12 months) | PFS was defined as the time period in months from the start of study drug treatment to the first of either progression or death. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
Countries
Philippines, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Erlotinib Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity. | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Failure to return | 1 |
| Overall Study | Insufficient therapeutic response | 44 |
Baseline characteristics
| Characteristic | Bevacizumab + Erlotinib |
|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 14.8 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 51 / 51 |
| serious Total, serious adverse events | 19 / 51 |
Outcome results
Primary
Percentage of Participants With Progression-free Survival (PFS)
Percentage of participants who were alive and without documented progressive disease 16 weeks after their first dose of study drug. Diagnosis of Progressive Disease was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Week 16
Population: Intent-to-treat population included all participants who received study drug. Participants who had neither progressed nor died at the time of study completion or who were lost to follow-up were censored at the date of the last tumor assessment or last follow up for progression of disease.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Erlotinib | Percentage of Participants With Progression-free Survival (PFS) | 35.3 percentage of participants |
Secondary
Disease Control Rate (DCR)
Disease Control Rate was defined as the percentage of participants with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at least 8 weeks by Response Evaluation Criteria in Solid Tumours (RECIST). CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; for non-target lesions persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.
Time frame: Event driven (median follow-up 12 months)
Population: Intent-to-treat population included all participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Erlotinib | Disease Control Rate (DCR) | 52.9 Percentage of participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time frame: Up to 107 Weeks
Population: Safety population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Erlotinib | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 19 participants |
| Bevacizumab + Erlotinib | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 51 participants |
Secondary
Overall Response Rate (ORR)
ORR was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR). Analysis of tumor response was based on the best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST), which was defined as the best response recorded from the start of trial treatment until disease progression/recurrence (or death), taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. PD required at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Event driven (median follow-up 12 months)
Population: Intent-to-treat population included all participants who received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Erlotinib | Overall Response Rate (ORR) | Complete Response | 0.0 percentage of participants |
| Bevacizumab + Erlotinib | Overall Response Rate (ORR) | Partial Response | 5.9 percentage of participants |
Secondary
Overall Survival (OS)
OS was defined as the time period in months from the start of study drug treatment to death.
Time frame: Event driven (median follow-up 12 months)
Population: Intent-to-treat population included all participants who received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Erlotinib | Overall Survival (OS) | 10.7 months |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time period in months from the start of study drug treatment to the first of either progression or death. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Event driven (median follow-up 12 months)
Population: Intent-to-treat population included all participants who received study drug. Participants were censored at the last follow-up visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Erlotinib | Progression-free Survival (PFS) | 2.9 months |
Secondary
Time to Tumor Progression
Time to tumor progression was defined as the time period in months from the start of study drug treatment to disease progression. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Event driven (median follow-up 12 months)
Population: Intent-to-treat population included all participants who received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Erlotinib | Time to Tumor Progression | 2.9 Months |