Breast Cancer
Conditions
Brief summary
The purpose of this study is to determine efficacy and safety of paclitaxel, bevacizumab and enzastaurin versus paclitaxel, bevacizumab, and placebo in participants who are diagnosed with locally recurrent or metastatic breast cancer.
Interventions
DRUGEnzastaurin
1125 milligrams (mg) loading dose on Day 1 of Cycle 1 only then 500 mg oral once daily, until disease progression
DRUGBevacizumab
10 milligrams per kilogram (mg/kg) intravenously, Days 1 and 15 every 28 days, until disease progression
DRUGPaclitaxel
90 milligrams per square meter (mg/m\^2), intravenously, Days 1 ,8, and 15 every 28 days until disease progression
DRUGPlacebo
Oral, daily, until disease progression
Sponsors
Genentech, Inc.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have signed an inform consent document * Have histologic or cytologic diagnosis of breast cancer with evidence of unresectable locally recurrent or metastatic disease * Have not received any prior chemotherapy for locally recurrent or metastatic disease * Have not had adjuvant or neoadjuvant taxane therapy within 12 months prior to assignment to study treatment * Age 18 years or older at time of informed consent
Exclusion criteria
* Have any clinical evidence of central nervous system (CNS) metastases * Have a history of seizure * Have had a major surgical procedure within 4 weeks prior to assignment to study treatment * Have had a minor surgical procedure, placement of an access device, or fine needle aspiration within 7 days prior to assignment to study treatment * Have symptomatic peripheral vascular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline to measured PD (up to 15 days) | PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Baseline to measured Progressive disease (up to 15 days) | ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR), assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). CR was defined as the disappearance of all tumor lesions; PR was defined as either ≥30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions. In either case of PR, no new lesions should have appeared. The percentage of participants with ORR was calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100. No participant completed a full cycle of therapy and thus no formal analysis was performed. |
| Number of Participants With Adverse Events (AEs) or Any Serious AEs (SAEs) | Baseline to study completion (Day 15) plus 30-day safety follow-up | A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. |
Countries
United States
Participant flow
Pre-assignment details
This study consisted of a safety lead-in prior to randomization. The study was terminated prior to completion of safety lead-in period.
Participants by arm
| Arm | Count |
|---|---|
| Enzastaurin + Bevacizumab + Paclitaxel Safety Lead-in Period: Enzastaurin 1125 milligrams (mg) loading dose (total nine 125-mg tablets: 3 tablets, 3 times daily) administered orally, only on Day 1 of Cycle 1, followed by 500 mg (four 125-mg tablets) administered orally, once daily in a 28-day cycle plus bevacizumab 10 milligrams per kilogram (mg/kg) administered intravenously on Days 1 and 15 of every 28-day cycle plus paclitaxel 90 milligrams per square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of every 28-day cycle. Participants were to receive enzastaurin, bevacizumab and paclitaxel for 2 cycles (1 cycle = 28 days).
Randomization Period: Participants were to receive the same treatment as administered during the safety lead-in period. Treatment was to continue until there was evidence of disease progression or intolerable toxicity. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other Complicating Disease | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Enzastaurin + Bevacizumab + Paclitaxel |
|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 16.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized White | 2 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed.
Time frame: Baseline to measured PD (up to 15 days)
Population: No participant completed a full cycle of therapy and data were not collected for this Outcome Measure.
Secondary
Number of Participants With Adverse Events (AEs) or Any Serious AEs (SAEs)
A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time frame: Baseline to study completion (Day 15) plus 30-day safety follow-up
Population: All enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzastaurin + Bevacizumab + Paclitaxel | Number of Participants With Adverse Events (AEs) or Any Serious AEs (SAEs) | Adverse Events (AEs) | 2 Participants |
| Enzastaurin + Bevacizumab + Paclitaxel | Number of Participants With Adverse Events (AEs) or Any Serious AEs (SAEs) | Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Overall Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR), assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). CR was defined as the disappearance of all tumor lesions; PR was defined as either ≥30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions. In either case of PR, no new lesions should have appeared. The percentage of participants with ORR was calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100. No participant completed a full cycle of therapy and thus no formal analysis was performed.
Time frame: Baseline to measured Progressive disease (up to 15 days)
Population: No participant completed a full cycle of therapy and data were not collected for this Outcome Measure.