Colorectal Cancer
Conditions
Brief summary
This expanded access study will assess the safety and efficacy of intravenous bevacizumab (5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks) in combination with fluoropyrimidine-based chemotherapy as first line treatment in participants with metastatic cancer of the colon or rectum. The anticipated time on study treatment is 3-12 months.
Interventions
DRUGBevacizumab
5 mg/kg bevacizumab administered intravenously every 2 weeks or 7.5 mg/kg bevacizumab administered intravenously every 3 weeks according to the standard chemotherapy regimen.
Fluoropyrimidine-based chemotherapy administered according to standard of care.
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
* Previously untreated metastatic colon or rectal cancer; * Scheduled to begin fluoropyrimidine-based chemotherapy as a first line treatment.
Exclusion criteria
* Prior chemotherapy for metastatic colon or rectal cancer; * Planned radiotherapy for underlying disease; * central nervous system metastases; * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before study start.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Number of Participants With Serious and Specific Adverse Events | Up to approximately 3 years | A serious adverse event was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. Specific adverse events (Spec AEs) included the following: hypertension, bleeding/hemorrhage, proteinuria, wound healing complications, thrombosis/thrombus/embolism (t/t/e), thrombosis/thrombus/embolism - vascular access, gastrointestinal perforation, and infusion (injection) site reaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Overall Survival | Up to approximately 3 years | Overall survival was measured as the time from start of first bevacizumab administration to death. For participants who were alive at the end of the study, data on survival were censored at the time of the last contact. Reported is the median duration of overall survival. |
| Efficacy: Time to Disease Progression | Up to approximately 3 years | Time to disease progression was measured as the time from start of first bevacizumab administration to investigator-assessed progression. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. For participants without disease progression at the end of the study, date and time to progression were censored at the last investigator assessment. Reported is the median time to disease progression. |
| Efficacy: Progression-free Survival | Up to approximately 3 years | Progression-free survival (PFS) was measured as the time from start of first bevacizumab administration to investigator-assessed progression or death, whichever occurred first. Progression was defined using RECIST v1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Reported is the median time of PFS. |
Countries
Brazil
Participant flow
Pre-assignment details
168 participants were enrolled in the study of which 162 received at least one dose of study drug. Only those who received at least one dose of study medication were included in the Intent to Treat (ITT) population, which is the population reported.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab Bevacizumab (5 mg/kg intravenously every 2 weeks or 7.5 mg/kg intravenously every 3 weeks) was administered in combination with fluoropyrimidine-based chemotherapy as first line treatment in participants with metastatic cancer of the colon or rectum until disease progression or study completion. | 162 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 25 |
| Overall Study | Disease progression | 98 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Medical Decision | 7 |
| Overall Study | Need for Surgery | 4 |
| Overall Study | Non-compliance | 2 |
| Overall Study | Partial response | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Stable Disease | 4 |
| Overall Study | Withdrawal of Consent | 8 |
Baseline characteristics
| Characteristic | Bevacizumab |
|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 13.1 |
| Gender Female | 89 Participants |
| Gender Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 153 / 162 |
| serious Total, serious adverse events | 50 / 162 |
Outcome results
Primary
Safety: Number of Participants With Serious and Specific Adverse Events
A serious adverse event was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. Specific adverse events (Spec AEs) included the following: hypertension, bleeding/hemorrhage, proteinuria, wound healing complications, thrombosis/thrombus/embolism (t/t/e), thrombosis/thrombus/embolism - vascular access, gastrointestinal perforation, and infusion (injection) site reaction.
Time frame: Up to approximately 3 years
Population: The intent to treat (ITT) population included all participants receiving at least one dose of the study drug. This population was primarily used for the reporting of safety information.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Serious Adverse Events | 50 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs: Hypertension | 57 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs: Proteinuria | 22 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs:Wound healing complications | 6 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs: Thrombosis/thrombus/embolism | 5 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs: T/t/e - Vascular Access | 2 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs: Gastrointestinal perforation | 2 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs: Infusion (injection) Site Reaction | 2 participants |
| Bevacizumab | Safety: Number of Participants With Serious and Specific Adverse Events | Spec AEs: Bleeding/hemorrhage | 42 participants |
Secondary
Efficacy: Overall Survival
Overall survival was measured as the time from start of first bevacizumab administration to death. For participants who were alive at the end of the study, data on survival were censored at the time of the last contact. Reported is the median duration of overall survival.
Time frame: Up to approximately 3 years
Population: 158 participants from the ITT population were included in the analysis. Four participants were excluded from the ITT population due to protocol deviation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Efficacy: Overall Survival | 21.6 months |
Secondary
Efficacy: Progression-free Survival
Progression-free survival (PFS) was measured as the time from start of first bevacizumab administration to investigator-assessed progression or death, whichever occurred first. Progression was defined using RECIST v1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Reported is the median time of PFS.
Time frame: Up to approximately 3 years
Population: 158 participants from the ITT population were included in the analysis. Four participants were excluded from the ITT population due to protocol deviation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Efficacy: Progression-free Survival | 11.0 months |
Secondary
Efficacy: Time to Disease Progression
Time to disease progression was measured as the time from start of first bevacizumab administration to investigator-assessed progression. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. For participants without disease progression at the end of the study, date and time to progression were censored at the last investigator assessment. Reported is the median time to disease progression.
Time frame: Up to approximately 3 years
Population: 158 participants from the ITT population were included in the analysis. Four participants were excluded from the ITT population due to protocol deviation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Efficacy: Time to Disease Progression | 11.4 months |