Cancer
Conditions
Keywords
cancer, colorectal cancer, ABT-165, FOLFIRI, Bevacizumab, bowel cancer, metastatic colorectal cancer, metastatic colorectal
Brief summary
A study to evaluate the efficacy and tolerability of ABT-165 plus FOLFIRI compared to bevacizumab plus FOLFIRI in participants with previously treated metastatic adenocarcinoma of the colon or rectum.
Interventions
DRUGLeucovorin
Intravenous
DRUGFluorouracil - bolus
Intravenous
DRUGBevacizumab
Intravenous
DRUGFluorouracil - infusion
Intravenous
DRUGABT-165
Intravenous
DRUGIrinotecan
Intravenous
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum. * Primary tumor has been resected \> 3 months prior to randomization. * At least 1 lesion on a computed tomography (CT) scan (preferred) or magnetic resonance imaging (MRI) that is measurable as defined by Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1. * Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. * Progression following treatment with fluoropyrimidine/oxaliplatin/bevacizumab-regimen in the metastatic setting. * Adequate hematologic, renal and hepatic function.
Exclusion criteria
* Any prior therapy with irinotecan * Unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) =\> Grade 2 * Clinically significant conditions that increase the risk for antiangiogenic therapy. * History of any of the following during first-line therapy with a bevacizumab-containing regimen: arterial thrombotic/thromboembolic event, bowel perforation, Grade 4 hypertension, Grade 3 proteinuria or Grade 3 - 4 bleeding event.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively | PFS is defined as the time from randomization until the first occurrence of radiographic progression determined by investigator assessment or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From randomization up to 30 days after last dose of study drug; median time on follow-up was 25.6 (0.3 - 64.4) and 37.6 (0.3 - 66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab plus FOLFIRI, respectively | ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) as determined by a investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. |
| Overall Survival (OS) | Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively | OS is defined as the time from randomization until death from any cause. |
Countries
Belgium, Canada, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
The intent to treat (ITT) population included all randomized participants and was used for all efficacy and baseline analyses.
Pre-assignment details
A total of 70 participants were randomized to 1 of the 2 study treatments. Participants were grouped according to treatment as randomized.
Participants by arm
| Arm | Count |
|---|---|
| ABT-165 Plus FOLFIRI ABT-165 plus FOLFIRI (irinotecan, leucovorin, fluorouracil) IV infusion for a 14 day cycle until disease progression or intolerable toxicity | 36 |
| Bevacizumab Plus FOLFIRI Bevacizumab plus FOLFIRI (irinotecan, leucovorin, fluorouracil) IV infusion for a 14 day cycle until disease progression or intolerable toxicity | 34 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 12 | 6 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Study terminated by Sponsor | 18 | 23 |
| Overall Study | Withdrew Consent | 5 | 4 |
Baseline characteristics
| Characteristic | ABT-165 Plus FOLFIRI | Bevacizumab Plus FOLFIRI | Total |
|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 11.41 | 60.2 years STANDARD_DEVIATION 10.19 | 60.5 years STANDARD_DEVIATION 10.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 31 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 21 Participants | 19 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 34 | 6 / 32 |
| other Total, other adverse events | 32 / 34 | 31 / 32 |
| serious Total, serious adverse events | 17 / 34 | 8 / 32 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is defined as the time from randomization until the first occurrence of radiographic progression determined by investigator assessment or death from any cause.
Time frame: Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively
Population: Intent to Treat (ITT): includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABT-165 Plus FOLFIRI | Progression Free Survival (PFS) | 3.78 Months |
| Bevacizumab Plus FOLFIRI | Progression Free Survival (PFS) | 7.36 Months |
Secondary
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) as determined by a investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
Time frame: From randomization up to 30 days after last dose of study drug; median time on follow-up was 25.6 (0.3 - 64.4) and 37.6 (0.3 - 66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab plus FOLFIRI, respectively
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-165 Plus FOLFIRI | Objective Response Rate (ORR) | 5.6 percentage of participants |
| Bevacizumab Plus FOLFIRI | Objective Response Rate (ORR) | 14.7 percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the time from randomization until death from any cause.
Time frame: Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABT-165 Plus FOLFIRI | Overall Survival (OS) | 7.95 Months |
| Bevacizumab Plus FOLFIRI | Overall Survival (OS) | NA Months |