Trial Outcomes & Findings for Trial of Paclitaxel, Bevacizumab, and Enzastaurin Versus Paclitaxel, Bevacizumab and Placebo for Breast Cancer (NCT NCT00536939)
NCT ID: NCT00536939
Last Updated: 2020-09-24
Results Overview
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.
TERMINATED
PHASE2
2 participants
Baseline to measured PD (up to 15 days)
2020-09-24
Participant Flow
This study consisted of a safety lead-in prior to randomization. The study was terminated prior to completion of safety lead-in period.
Participant milestones
| Measure |
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.
|
Bevacizumab + Paclitaxel + Placebo
Safety lead-in Period: No treatment
Randomization Period: Participants were to receive bevacizumab 10 mg/kg administered intravenously on Days 1 and 15 of every 28-day cycle plus paclitaxel 90 mg/m\^2 administered intravenously on Days 1, 8 and 15 of every 28-day cycle plus placebo loading dose administered orally (total 9 tablets: 3 tablets, 3 times daily) only on Day 1 of Cycle 1, followed by oral administration once daily in a 28-day cycle. Treatment was to continue until there was disease progression or intolerable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
2
|
0
|
|
Overall Study
Entered Safety lead-in
|
2
|
0
|
|
Overall Study
Randomized
|
0
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
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.
|
Bevacizumab + Paclitaxel + Placebo
Safety lead-in Period: No treatment
Randomization Period: Participants were to receive bevacizumab 10 mg/kg administered intravenously on Days 1 and 15 of every 28-day cycle plus paclitaxel 90 mg/m\^2 administered intravenously on Days 1, 8 and 15 of every 28-day cycle plus placebo loading dose administered orally (total 9 tablets: 3 tablets, 3 times daily) only on Day 1 of Cycle 1, followed by oral administration once daily in a 28-day cycle. Treatment was to continue until there was disease progression or intolerable toxicity.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Other Complicating Disease
|
1
|
0
|
Baseline Characteristics
Trial of Paclitaxel, Bevacizumab, and Enzastaurin Versus Paclitaxel, Bevacizumab and Placebo for Breast Cancer
Baseline characteristics by cohort
| Measure |
Enzastaurin + Bevacizumab + Paclitaxel
n=2 Participants
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.
|
|---|---|
|
Age, Continuous
|
56.5 years
STANDARD_DEVIATION 16.26 • n=99 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
2 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
2 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to study completion (Day 15) plus 30-day safety follow-upPopulation: All enrolled participants.
A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Outcome measures
| Measure |
Enzastaurin + Bevacizumab + Paclitaxel
n=2 Participants
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.
|
|---|---|
|
Number of Participants With Adverse Events (AEs) or Any Serious AEs (SAEs)
Adverse Events (AEs)
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs) or Any Serious AEs (SAEs)
Serious Adverse Events (SAEs)
|
0 Participants
|
Adverse Events
Enzastaurin + Bevacizumab + Paclitaxel
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Enzastaurin + Bevacizumab + Paclitaxel
n=2 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
50.0%
1/2 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Oedema peripheral
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Pain
|
50.0%
1/2 • Number of events 2
|
|
Infections and infestations
Infection
|
50.0%
1/2 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
50.0%
1/2 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
50.0%
1/2 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
50.0%
1/2 • Number of events 1
|
|
Nervous system disorders
Headache
|
50.0%
1/2 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60