Colorectal Cancer
Conditions
Brief summary
This study will assess the efficacy and safety of intravenous Avastin in combination with chemotherapy regimens as second-line treatment of metastatic cancer of the colon or rectum. The anticipated time of study treatment is until disease progression.
Interventions
DRUGbevacizumab [Avastin]
5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks according to the chemotherapy regimen
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
* Patients with metastatic colon or rectal cancer, progressing or relapsing after first-line treatment; * Women of childbearing potential must use adequate contraception up to at least 6 months after the last dose of bevacizumab.
Exclusion criteria
* Patients with metastatic colon or rectal cancer scheduled for a first-line systemic treatment; * Untreated brain metastases, spinal cord compression or primary brain tumours; * Pregnant or lactating women; * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study start; * Treatment with any investigational drug, or participation in another investigational study, within 30 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Overall Disease Control (ODC) | Baseline, after every other cycle to disease progression or death (Maximum of 52.5 months follow-up) | ODC was defined as the percentage of participants with measurable disease at baseline who on assessment achieved complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. CR and PR were confirmed no less than 4 weeks after the criteria for response were met. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) - Percentage of Participants With an Event | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | PFS was defined as the time from start of study treatment to investigator assessed disease progression, or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to RECIST. |
| PFS - Time to Event | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | PFS was defined as the time from start of study treatment to investigator assessed disease progression, or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to RECIST. Median PFS was estimed using the Kaplan-Meier method. |
| Duration of Response | Baseline, every cycle until progression or death (Maximum of 52.5 months follow-up) | Duration of response was defined as the time in months from the day of CR or PR was first noted to the day of progression of disease, death or last follow-up. Median duraiton of response is estimated sing the Kaplan-Meier method. |
| Percentage of Participants Achieving a Best Overall Response of CR or PR | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | Percentage of participants achieving CR or PR as defined by RECIST criteria. CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. CR and PR were confirmed no less than 4 weeks after the criteria for response were met. |
| Overall Survival (OS) - Percentage of Participants With an Event | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | Overall survival was defined as the time from start of study treatment to death from any cause. |
| OS - Time to Event | Baseline, every cycle to progression or death. (Maximum of 52.5 months follow-up) | OS was defined as the time from start of study treatment to death from any cause. Median OS was estimated using the Kaplan-Meier method. |
| Duration of Overall Disease Control | Baseline, every cycle until progression or death. (Maximum of 52.5 months follow-up) | ODC duration was defined as the time in months, from when measurement criteria were first met for CR, PR, or SD (whichever status was recorded first) until the first date when progressive disease or the death from any cause was documented. Data were censored for participants who were lost to follow-up, discontinued prematurely without progression/death, or who reached the end of study without progression. Median ODC was estimated using the Kaplan-Meier method. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Chemotherapy Participants received bevacizumab 2.5 mg/kg IV per week, either as 5 mg/kg on Day 1 of a 2-week cycle or as 7.5 mg/kg on Day 1 of a 3-week cycle and was dependent on the chemotherapy regimen used. The choice of chemotherapy regimen was left to the discretion of the investigator per standard of care at the study site. Cycle was repeated until disease progression or withdrawal of participant. | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 50 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Bevacizumab + Chemotherapy |
|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 53 |
| serious Total, serious adverse events | 9 / 53 |
Outcome results
Primary
Percentage of Participants Achieving Overall Disease Control (ODC)
ODC was defined as the percentage of participants with measurable disease at baseline who on assessment achieved complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. CR and PR were confirmed no less than 4 weeks after the criteria for response were met.
Time frame: Baseline, after every other cycle to disease progression or death (Maximum of 52.5 months follow-up)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Percentage of Participants Achieving Overall Disease Control (ODC) | 87 percentage of participants |
Secondary
Duration of Overall Disease Control
ODC duration was defined as the time in months, from when measurement criteria were first met for CR, PR, or SD (whichever status was recorded first) until the first date when progressive disease or the death from any cause was documented. Data were censored for participants who were lost to follow-up, discontinued prematurely without progression/death, or who reached the end of study without progression. Median ODC was estimated using the Kaplan-Meier method.
Time frame: Baseline, every cycle until progression or death. (Maximum of 52.5 months follow-up)
Population: ITT population; only participants with an ODC response (CR, PR, or SD) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | Duration of Overall Disease Control | 6.7 months |
Secondary
Duration of Response
Duration of response was defined as the time in months from the day of CR or PR was first noted to the day of progression of disease, death or last follow-up. Median duraiton of response is estimated sing the Kaplan-Meier method.
Time frame: Baseline, every cycle until progression or death (Maximum of 52.5 months follow-up)
Population: ITT population; only participants with a response (CR or PR) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | Duration of Response | 6 months |
Secondary
OS - Time to Event
OS was defined as the time from start of study treatment to death from any cause. Median OS was estimated using the Kaplan-Meier method.
Time frame: Baseline, every cycle to progression or death. (Maximum of 52.5 months follow-up)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | OS - Time to Event | 19.3 months |
Secondary
Overall Survival (OS) - Percentage of Participants With an Event
Overall survival was defined as the time from start of study treatment to death from any cause.
Time frame: Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Overall Survival (OS) - Percentage of Participants With an Event | 93.0 percentage of participants |
Secondary
Percentage of Participants Achieving a Best Overall Response of CR or PR
Percentage of participants achieving CR or PR as defined by RECIST criteria. CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. CR and PR were confirmed no less than 4 weeks after the criteria for response were met.
Time frame: Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Percentage of Participants Achieving a Best Overall Response of CR or PR | 32 percentage of participants |
Secondary
PFS - Time to Event
PFS was defined as the time from start of study treatment to investigator assessed disease progression, or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to RECIST. Median PFS was estimed using the Kaplan-Meier method.
Time frame: Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | PFS - Time to Event | 6.5 months |
Secondary
Progression-Free Survival (PFS) - Percentage of Participants With an Event
PFS was defined as the time from start of study treatment to investigator assessed disease progression, or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to RECIST.
Time frame: Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up)
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Progression-Free Survival (PFS) - Percentage of Participants With an Event | 98 percentage of participants |