Trial Outcomes & Findings for A Trial of 2 Schedules of Ixabepilone Plus Bevacizumab and Paclitaxel Plus Bevacizumab for Breast Cancer (NCT NCT00370552)

Last Updated: 2016-03-10

Results Overview

CR=Disappearance of all clinical and radiologic evidence of target lesions; PR=At least 30% reduction in the sum of the longest diameter of all target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

136 participants

Primary outcome timeframe

Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression

Results posted on

2016-03-10

Participant Flow

Of the 136 participants enrolled in this study, 123 were randomized. Of the 13 not randomized, 11 no longer met study criteria, 1 withdrew, and 1 was found to have extensive disease. Of the 123 randomized, 122 were treated, and 1 no longer met study criteria and was never treated.

Participant milestones

Participant milestones
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Overall Study STARTED	46	45	32
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	46	45	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Overall Study Adverse Event	2	2	2
Overall Study Disease progression	23	23	15
Overall Study Maximum clinical benefit	3	5	5
Overall Study Poor or noncompliance	0	0	1
Overall Study Study drug toxicity	11	8	6
Overall Study Withdrawal by Subject	2	0	1
Overall Study Still on treatment	1	3	2
Overall Study Never treated	1	0	0
Overall Study Physician Decision	1	1	0
Overall Study Investigator decision	2	1	0
Overall Study High risk of allergic reaction	0	1	0
Overall Study Planned radiation for palliation	0	1	0

Baseline Characteristics

A Trial of 2 Schedules of Ixabepilone Plus Bevacizumab and Paclitaxel Plus Bevacizumab for Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=46 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Total n=123 Participants Total of all reporting groups
Age, Continuous	60.0 years n=5 Participants	59.0 years n=7 Participants	59.0 years n=5 Participants	59.0 years n=4 Participants
Age, Customized Younger than 65 years	33 participants n=5 Participants	29 participants n=7 Participants	22 participants n=5 Participants	84 participants n=4 Participants
Age, Customized >=65 years	13 participants n=5 Participants	16 participants n=7 Participants	10 participants n=5 Participants	39 participants n=4 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	45 Participants n=7 Participants	32 Participants n=5 Participants	123 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants	40 Participants n=7 Participants	31 Participants n=5 Participants	114 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression

Population: All randomized participants

CR=Disappearance of all clinical and radiologic evidence of target lesions; PR=At least 30% reduction in the sum of the longest diameter of all target lesions.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=46 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study	47.8 Percentage of participants Interval 32.9 to 63.1	71.1 Percentage of participants Interval 55.7 to 83.6	62.5 Percentage of participants Interval 43.7 to 78.9

PRIMARY outcome

Timeframe: Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression

Population: All randomized participants

Best tumor response was assessed with RECIST. Complete response (CR)=Disappearance of all evidence of target lesions; Partial response (PR)=At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions; Progressive disease (PD)=At least a 20% increase from baseline in the sum of LD of target lesions or the appearance of 1 or more new lesions; Stable disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. A response was confirmed if noted on 2 examinations at least 4 weeks apart.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=46 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) Complete Response	2 Participants	2 Participants	4 Participants
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) Partial Response	20 Participants	30 Participants	16 Participants
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) Stable Disease	18 Participants	9 Participants	11 Participants
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) Progressive Disease	5 Participants	3 Participants	0 Participants
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) Unable to Determine	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Date of randomization to Week 24

Population: All randomized participants

Week 24 Progression-free Survival was defined as the number of participants who neither progressed nor died before Week 24. Computed using Kaplan-Meier estimates, only at the time of Interim Analysis, when all participants had been followed for 6 months.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=46 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Percentage of Participants With Progression-free Survival at Week 24	75 Percentage of participants Interval 62.37 to 87.87	86 Percentage of participants Interval 75.72 to 96.42	94 Percentage of participants Interval 85.36 to 100.0

SECONDARY outcome

Timeframe: Date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 29 months)

Population: All randomized participants.

PFS was defined as the time from randomization to progression or to death from any cause without prior documentation of progression. Participants who did not progress or die were to be censored on the date of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=46 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Median Progression-free Survival (PFS)	9.6 Months Interval 6.1 to 11.7	11.9 Months Interval 8.7 to 14.7	13.5 Months Interval 10.0 to 18.2

SECONDARY outcome

Timeframe: Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant time to response of 67 weeks)

Population: Participants whose best response was CR or PR, as assessed by the investigator.

Time to response was defined as the time from the first dose of study therapy until measurement criteria were first met for a PR or CR, whichever was recorded first. Time to response was computed only for participants whose best response was PR or CR.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=22 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=32 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=20 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Median Time to Response	8.2 Weeks Interval 6.1 to 67.0	8.3 Weeks Interval 5.3 to 37.9	8.1 Weeks Interval 7.0 to 32.0

SECONDARY outcome

Timeframe: Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 25 weeks)

Population: Participants whose best response was CR or PR, as assessed by the investigator.

Duration of response was computed for participants whose best response was either PR or CR. Duration of overall response was defined as the period from the time that measurement criteria were first met for PR or CR, whichever was recorded first, until the first date of documented PD or death. Participants who neither relapsed nor died were to be censored on the date of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=22 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=32 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=20 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Median Duration of Response	10.1 Months Interval 7.3 to 14.5	10.3 Months Interval 9.0 to 14.3	13.1 Months Interval 9.2 to 21.7

SECONDARY outcome

Timeframe: Date first participant enrolled to 1 year

Population: All randomized participants.

One year survival rates were computed using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=46 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Percentage of Participants Surviving at 1 Year	91 Percentage of participants Interval 82.69 to 99.42	89 Percentage of participants Interval 79.71 to 98.07	91 Percentage of participants Interval 80.53 to 100.0

SECONDARY outcome

Timeframe: At initiation of treatment throughout study, to a minimum of 30 days after last dose of study drug

Population: All randomized participants who received any study drug.

An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency or abuse; is life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=45 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs Deaths	12 Participants	15 Participants	5 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs SAEs	15 Participants	16 Participants	9 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs Treatment-related SAEs	7 Participants	9 Participants	5 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs Treatment-related AEs Leading to Discontinuation	24 Participants	23 Participants	20 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs AEs Leading to Discontinuation	26 Participants	25 Participants	21 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs Treatment-related AEs	43 Participants	45 Participants	32 Participants

SECONDARY outcome

Timeframe: At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle

Population: All randomized participants who received any study drug.

CTC, Version 3 used to assess parameters. CTC Gr=Grade; WBC=white blood cells; ANC=absolute neutrophil count. LLN=lower level of normal. WBC Gr 1:\<LLN to 3.0\*10\^9/L, Gr 2:\<3.0 to 2.0\*10\^9/L, Gr 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L; ANC Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L; Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L; Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=45 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=45 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade White blood cells (WBC) (Grade 1)	11 Participants	12 Participants	12 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade WBC (Grade 2)	14 Participants	12 Participants	11 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade WBC (Grade 3)	1 Participants	14 Participants	3 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade WBC (Grade 4)	2 Participants	4 Participants	0 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Absolute neutrophil count (ANC) (Grade 1)	10 Participants	4 Participants	6 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade ANC (Grade 2)	9 Participants	10 Participants	13 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade ANC (Grade 3)	5 Participants	17 Participants	6 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade ANC (Grade 4)	2 Participants	10 Participants	1 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Platelet count (Grade 1)	4 Participants	15 Participants	3 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Platelet count (Grade 2)	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Platelet count (Grade 3)	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Platelet count (Grade 4)	2 Participants	1 Participants	0 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Hemoglobin (Grade 1)	21 Participants	20 Participants	17 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Hemoglobin (Grade 2)	3 Participants	4 Participants	3 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Hemoglobin (Grade 3)	1 Participants	3 Participants	2 Participants
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade Hemoglobin (Grade 4)	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle

Population: All randomized participants who received any study drug and had samples available.

ULN=Upper limit of normal.ALT Gr 1:\>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; AST Gr 1: \>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; ALP Gr 1:\>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; Total bilirubin Gr 1: \>ULN to 1.5\*ULN, Gr 2: \>1.5 to 3.0\*ULN, Gr 3: \>3.0 to 10.0\*ULN, Gr 4: \>10.0\*ULN.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=43 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=44 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade Alanine aminotransferase (ALT) (Grade 1)	18 Participants	13 Participants	13 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade ALT (Grade 2)	2 Participants	4 Participants	3 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade ALT (Grade 3)	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade ALT (Grade 4)	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade AST (Grade 1)	20 Participants	18 Participants	15 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade AST (Grade 2)	1 Participants	1 Participants	1 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade AST (Grade 3)	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade AST (Grade 4)	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade Alkaline phosphatase (ALP) (Grade 1)	8 Participants	11 Participants	12 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade ALP (Grade 2)	0 Participants	3 Participants	0 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade ALP (Grade 3)	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade ALP (Grade 4)	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade Total bilirubin (Grade 1)	3 Participants	3 Participants	2 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade Total bilirubin (Grade 2)	2 Participants	0 Participants	1 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade Total bilirubin (Grade 3)	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade Total bilirubin (Grade 4)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle

Population: All randomized participants who received any study drug and had samples available.

Creatine Gr 1: \>ULN to 1.5\*ULN, Gr 2: 1.5 to 3.0\*ULN, Gr 3: \>3.0 to 6.0\*ULN, Gr 4: \>6.0\*ULN.

Outcome measures

Outcome measures
Measure	Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg n=44 Participants Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg n=44 Participants Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.	Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg n=32 Participants Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Number of Participants With Abnormalities in Renal Function by Worst CTC Grade Creatinine (Grade 2)	3 Participants	1 Participants	0 Participants
Number of Participants With Abnormalities in Renal Function by Worst CTC Grade Creatinine (Grade 1)	5 Participants	3 Participants	3 Participants
Number of Participants With Abnormalities in Renal Function by Worst CTC Grade Creatinine (Grade 3)	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormalities in Renal Function by Worst CTC Grade Creatinine (Grade 4)	0 Participants	0 Participants	0 Participants

Adverse Events

Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg

Serious events: 15 serious events

Other events: 45 other events

Deaths: 0 deaths

Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg

Serious events: 16 serious events

Other events: 45 other events

Deaths: 0 deaths

Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg

Serious events: 9 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period of 60 days or less from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER