Colorectal Cancer
Conditions
Brief summary
This single arm study will evaluate the efficacy and safety of a first-line regimen of Avastin and XELOX (oxaliplatin + Xeloda) in patients with metastatic cancer of the colon or rectum. Patients will receive 21-day cycles of treatment, comprising Avastin 7.5mg/kg iv on day 1, oxaliplatin 130mg/m2 iv on day 1, and Xeloda 1000mg/m2 po twice daily on days 1-14, for a maximum of 6 months. Patients with stable disease or complete or partial response may continue on Avastin therapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Interventions
DRUGbevacizumab [Avastin]
7.5mg iv on day 1 of each 3 week cycle
DRUGOxaliplatin
130mg/m2 iv on day 1 of each 3 week cycle
DRUGXeloda
1000mg/m2 po bid on days 1-14 of each 3 week cycle
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; * locally advanced or metastatic colorectal cancer; * no previous treatment with chemotherapy for metastatic disease; * at least one measurable lesion.
Exclusion criteria
* radiotherapy to any site within 4 weeks before study; * untreated brain metastases or primary brain tumors; * clinically significant cardiovascular disease; * chronic daily treatment with high dose aspirin (\>325 mg/day); * other co-existing malignancies or malignancies diagnosed within last 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS): Percentage of Participants With Progressive Disease or Death | Baseline and Day 1 of every cycle until disease progression or death up to 5 years | PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented neither a relapse nor a new colorectal cancer had occurred. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20 percent (%) 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. |
| PFS: Time to Event | Baseline and Day 1 of every cycle until disease progression or death up to 5 years | PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented that neither a relapse nor a new colorectal cancer had occurred. Median PFS was estimated using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to CR or PR Overall Response - Time to Event | Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years | Time to overall response (CR or PR) was calculated as the time between the date of start of treatment until first documented response (CR or PR defined per RECIST v1.0). Participants who did not achieve CR or PR were censored at the date of progression, death, or at last adequate tumor assessment date. Median time to CR or PR overall response was estimated using the Kaplan-Meier method. |
| Percentage of Participants With a Best Overall Response of CR or PR During First Line Treatment | Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years | CR and PR were defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Duration of Overall Response Among Participants Whose Best Response Was CR or PR During First Line Treatment - Time to Event | Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years | For participants with a best overall response of CR or PR, the duration of overall response was measured from the time that the criteria for CR or PR (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of overall response was estimated using the Kaplan-Meier method. |
| Percentage of Participants With a Stable Response During First Line Treatment | Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years | Stable response defined as participants with a best overall response of CR, PR, or stable disease (SD), defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. |
| Duration of Stable Response | Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years | For participants with a best overall response of CR, PR, or SD during first line treatment, the duration of stable response was measured from the time that the criteria for CR, PR, or SD (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of stable response was estimated using the Kaplan-Meier method. |
| Percentage of Participants With Treatment Failure | Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years | Treatment-failure was defined as discontinuation of treatment for any reason, including the following qualifying events: death due to any cause, adverse event, insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent). |
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) Among Participants in the ITT Population Who Had at Least 1 Post-Baseline Assessment | Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years | The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than \[\<\]10 millimeters \[mm\]). No new lesions. PR was defined as a greater than or equal to (≥) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Overall Survival: Percentage of Participants That Died Due to Any Cause | Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years | Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive. |
| Overall Survival: Time to Event | Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years | Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive. Median overall survival was estimated using the Kaplan-Meier method. |
| Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | At surgery, at least 6 to 8 weeks after last dose of bevacizumab up to 5 years | The percentage of participants who underwent surgery during the study period with an evaluation of their disease status after surgery. The surgery during the study period was described by reason: curative, palliative, biopsy, other, or unknown. Residual disease status after surgery was described as: no residual disease due to radical surgery, presence of residual disease, unknown or not applicable. |
| Percentage of Participants With Best Overall Response of CR or PR by Kirsten Rat Sarcoma Viral Oncogene Homolog (K-Ras)/V-Raf Murine Sarcoma Viral Oncogene Homolog B (B-Raf) Mutation Status | Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years | The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. The K-Ras and/or the B-Raf gene mutation status of participants was evaluated by the central laboratory using tumor samples. Wild-type participants did not have a mutation in either gene. |
| European Quality of Life 5 Dimension (EQ-5D) Raw-Index Score | Baseline, every 9 weeks (every 3 cycles), at end-of-treatment up to 5 years | Quality of life (QoL) assessments were used to derive pre-specified QoL scores according to the QoL manual EQ-5D-3 Level (3L) user guide for instrument version 4.0. The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The visual analog scale (VAS) component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The overall health score absolute changes were calculated for each participant as follows: (score at the end of treatment minus score at baseline). EQ-5D health states were converted into EQ-5D-3L raw index value by applying the scoring algorithm based on the European EQ-net VAS set. The raw index was chosen instead of rescaled index, since the questionnaire was used in order to obtain a quality of life assessment. The raw index scores ranged from 0 (worst health state) to 100 (best health state). |
| Time to Treatment Failure | Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years | Time to treatment-failure was defined as the time from the first day of treatment to discontinuation of treatment for any reason, including: death due to any cause, adverse event, insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent). For participants who did not experience a qualifying event, their data were censored at the earlier of either the date of last tumour assessment or the date of the last intake of study medication. Median time to treatment-failure was estimated using the Kaplan-Meier method. |
| Percentage of Participants With a CR or PR Among Participants in the ITT Population | Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years | CR and PR were defined using RECIST v1.0. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.
Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression. | 197 |
| Total | 197 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 52 |
| Overall Study | Death | 6 |
| Overall Study | Medical decision | 14 |
| Overall Study | Need for surgery | 17 |
| Overall Study | Participant non-compliance | 5 |
| Overall Study | Participant withdrew consent | 13 |
| Overall Study | Progression of disease | 93 |
| Overall Study | Protocol Violation | 5 |
Baseline characteristics
| Characteristic | Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab |
|---|---|
| Age, Continuous | 62.25 years STANDARD_DEVIATION 9.94 |
| Sex: Female, Male Female | 86 Participants |
| Sex: Female, Male Male | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 179 / 197 |
| serious Total, serious adverse events | 56 / 197 |
Outcome results
Primary
PFS: Time to Event
PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented that neither a relapse nor a new colorectal cancer had occurred. Median PFS was estimated using the Kaplan-Meier method.
Time frame: Baseline and Day 1 of every cycle until disease progression or death up to 5 years
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | PFS: Time to Event | 9.70 months |
Primary
Progression-Free Survival (PFS): Percentage of Participants With Progressive Disease or Death
PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented neither a relapse nor a new colorectal cancer had occurred. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20 percent (%) 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.
Time frame: Baseline and Day 1 of every cycle until disease progression or death up to 5 years
Population: Intent-to-treat (ITT) population: all enrolled participants who received at least 1 dose of all study medications and had at least 1 measurable lesion according to the Response Evaluation Criteria In Solid Tumours (RECIST) criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Progression-Free Survival (PFS): Percentage of Participants With Progressive Disease or Death | 50.25 percentage of participants |
Secondary
Duration of Overall Response Among Participants Whose Best Response Was CR or PR During First Line Treatment - Time to Event
For participants with a best overall response of CR or PR, the duration of overall response was measured from the time that the criteria for CR or PR (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of overall response was estimated using the Kaplan-Meier method.
Time frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Population: ITT population, only those participants who achieved a best overall response of CR or PR during first line treatment were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Duration of Overall Response Among Participants Whose Best Response Was CR or PR During First Line Treatment - Time to Event | 8.52 months |
Secondary
Duration of Stable Response
For participants with a best overall response of CR, PR, or SD during first line treatment, the duration of stable response was measured from the time that the criteria for CR, PR, or SD (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of stable response was estimated using the Kaplan-Meier method.
Time frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Population: ITT population, only participants who achieved a best overall response of CR, PR, or SD during first line treatment were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Duration of Stable Response | 10.39 months |
Secondary
European Quality of Life 5 Dimension (EQ-5D) Raw-Index Score
Quality of life (QoL) assessments were used to derive pre-specified QoL scores according to the QoL manual EQ-5D-3 Level (3L) user guide for instrument version 4.0. The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The visual analog scale (VAS) component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The overall health score absolute changes were calculated for each participant as follows: (score at the end of treatment minus score at baseline). EQ-5D health states were converted into EQ-5D-3L raw index value by applying the scoring algorithm based on the European EQ-net VAS set. The raw index was chosen instead of rescaled index, since the questionnaire was used in order to obtain a quality of life assessment. The raw index scores ranged from 0 (worst health state) to 100 (best health state).
Time frame: Baseline, every 9 weeks (every 3 cycles), at end-of-treatment up to 5 years
Population: ITT population, only participants who had EQ-5D-3L scores for both baseline and last visit were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | European Quality of Life 5 Dimension (EQ-5D) Raw-Index Score | Baseline | 80.24 units on a scale | Standard Deviation 14.32 |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | European Quality of Life 5 Dimension (EQ-5D) Raw-Index Score | Last visit | 74.94 units on a scale | Standard Deviation 19.08 |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | European Quality of Life 5 Dimension (EQ-5D) Raw-Index Score | Absolute change from baseline | -5.30 units on a scale | Standard Deviation 19.13 |
Comparison: Change from baseline to last visitp-value: 0.0076Signed-rank test
Secondary
Overall Survival: Percentage of Participants That Died Due to Any Cause
Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive.
Time frame: Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Overall Survival: Percentage of Participants That Died Due to Any Cause | 50.76 percentage of participants |
Secondary
Overall Survival: Time to Event
Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive. Median overall survival was estimated using the Kaplan-Meier method.
Time frame: Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Overall Survival: Time to Event | 23.15 months |
Secondary
Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery
The percentage of participants who underwent surgery during the study period with an evaluation of their disease status after surgery. The surgery during the study period was described by reason: curative, palliative, biopsy, other, or unknown. Residual disease status after surgery was described as: no residual disease due to radical surgery, presence of residual disease, unknown or not applicable.
Time frame: At surgery, at least 6 to 8 weeks after last dose of bevacizumab up to 5 years
Population: The 52 participant subpopulation of the ITT population who underwent surgery during the time period of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Palliative, no residual disease | 3.85 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Palliative, residual disease | 7.69 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Curative, no residual disease | 55.77 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Curative, residual disease | 13.46 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Curative, unknown | 3.85 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Curative, not applicable | 7.69 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Palliative, unknown | 3.85 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Palliative, not applicable | 1.92 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Biopsy, residual disease | 1.92 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Biopsy, not applicable | 1.92 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Unknown, unknown | 1.92 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Unknown, not applicable | 3.85 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Other, residual disease | 1.92 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery | Other, not applicable | 3.85 percentage of participants |
Secondary
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) Among Participants in the ITT Population Who Had at Least 1 Post-Baseline Assessment
The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than \[\<\]10 millimeters \[mm\]). No new lesions. PR was defined as a greater than or equal to (≥) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
Population: Subset of participants in the ITT population who had at least 1 post-baseline tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) Among Participants in the ITT Population Who Had at Least 1 Post-Baseline Assessment | 58.79 percentage of participants |
Secondary
Percentage of Participants With a Best Overall Response of CR or PR During First Line Treatment
CR and PR were defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Population: ITT population, only those participants who achieved a best overall response of CR or PR during first line treatment were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants With a Best Overall Response of CR or PR During First Line Treatment | 54.64 percentage of participants |
Secondary
Percentage of Participants With a CR or PR Among Participants in the ITT Population
CR and PR were defined using RECIST v1.0. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants With a CR or PR Among Participants in the ITT Population | 49.24 percentage of participants |
Secondary
Percentage of Participants With a Stable Response During First Line Treatment
Stable response defined as participants with a best overall response of CR, PR, or stable disease (SD), defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.
Time frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Population: ITT population, only participants who achieved a best overall response of CR, PR, or SD during first line treatment were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants With a Stable Response During First Line Treatment | 52.63 percentage of participants |
Secondary
Percentage of Participants With Best Overall Response of CR or PR by Kirsten Rat Sarcoma Viral Oncogene Homolog (K-Ras)/V-Raf Murine Sarcoma Viral Oncogene Homolog B (B-Raf) Mutation Status
The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis \<10 mm). No new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. The K-Ras and/or the B-Raf gene mutation status of participants was evaluated by the central laboratory using tumor samples. Wild-type participants did not have a mutation in either gene.
Time frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
Population: ITT population; only participants with a known K-Ras and/or B-Raf gene mutation status and at least 1 post-baseline tumor assessment. Number (n) equals (=) number of participants with either wild-type or K-Ras/B-Raf gene mutation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants With Best Overall Response of CR or PR by Kirsten Rat Sarcoma Viral Oncogene Homolog (K-Ras)/V-Raf Murine Sarcoma Viral Oncogene Homolog B (B-Raf) Mutation Status | Wild-type (n=18) | 88.89 percentage of participants |
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants With Best Overall Response of CR or PR by Kirsten Rat Sarcoma Viral Oncogene Homolog (K-Ras)/V-Raf Murine Sarcoma Viral Oncogene Homolog B (B-Raf) Mutation Status | Gene mutation (n=15) | 66.67 percentage of participants |
Secondary
Percentage of Participants With Treatment Failure
Treatment-failure was defined as discontinuation of treatment for any reason, including the following qualifying events: death due to any cause, adverse event, insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent).
Time frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Percentage of Participants With Treatment Failure | 82.74 percentage of participants |
Secondary
Time to CR or PR Overall Response - Time to Event
Time to overall response (CR or PR) was calculated as the time between the date of start of treatment until first documented response (CR or PR defined per RECIST v1.0). Participants who did not achieve CR or PR were censored at the date of progression, death, or at last adequate tumor assessment date. Median time to CR or PR overall response was estimated using the Kaplan-Meier method.
Time frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Time to CR or PR Overall Response - Time to Event | 3.93 months |
Secondary
Time to Treatment Failure
Time to treatment-failure was defined as the time from the first day of treatment to discontinuation of treatment for any reason, including: death due to any cause, adverse event, insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent). For participants who did not experience a qualifying event, their data were censored at the earlier of either the date of last tumour assessment or the date of the last intake of study medication. Median time to treatment-failure was estimated using the Kaplan-Meier method.
Time frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab | Time to Treatment Failure | 6.69 months |