Trial Outcomes & Findings for Phase II Trial of Weekly or Every 3-week Ixabepilone for Patients With Metastatic Breast Cancer (NCT NCT00593827)

Last Updated: 2016-03-10

Results Overview

PFS at 6 months was defined as proportion of participants who neither progressed nor died before 6 months. Computed using Kaplan-Meier estimates.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

176 participants

Primary outcome timeframe

From the date of randomization to 6-months on study

Results posted on

2016-03-10

Participant Flow

A total of 176 participants were enrolled by 55 sites in the United States over a period of 12 months.

All the 176 enrolled participants were randomized. Of the 5 participants who did not receive treatment, 2 were due to disease progression, 1 on participant request, and 2 due to other reasons.

Participant milestones

Participant milestones
Measure	Ixabepilone 16 mg/m^2 ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 ixabepilone 40 mg/m\^2 every 3 weeks
Overall Study STARTED	85	91
Overall Study Safety Population	82	89
Overall Study Evaluable Population	79	89
Overall Study COMPLETED	85	89
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixabepilone 16 mg/m^2 ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 ixabepilone 40 mg/m\^2 every 3 weeks
Overall Study On Active Treatment/Pending	0	2

Baseline Characteristics

Phase II Trial of Weekly or Every 3-week Ixabepilone for Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixabepilone 16 mg/m^2 n=85 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=91 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Total n=176 Participants Total of all reporting groups
Age, Continuous	60.3 Years STANDARD_DEVIATION 11.4 • n=5 Participants	58.7 Years STANDARD_DEVIATION 10.4 • n=7 Participants	59.5 Years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	91 Participants n=7 Participants	176 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	69 Participants n=5 Participants	70 Participants n=7 Participants	139 Participants n=5 Participants
Race/Ethnicity, Customized African American	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	6 Participants n=5 Participants	11 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	85 Participants n=5 Participants	91 Participants n=7 Participants	176 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0=normal activity	39 Participants n=5 Participants	43 Participants n=7 Participants	82 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1=symptoms, but fully ambulatory	40 Participants n=5 Participants	43 Participants n=7 Participants	83 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 2=symptomatic, but in bed < 50% of the day	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization to 6-months on study

Population: ITT population: Participants who were randomized on the study (eligible and ineligible).

PFS at 6 months was defined as proportion of participants who neither progressed nor died before 6 months. Computed using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=85 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=91 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Progression-Free Survival (PFS) at 6 Months (6-month PFS Rate): Proportion of Participants Progression Free at 6 Months	28.6 Percentage of Participants Interval 18.9 to 38.9	42.7 Percentage of Participants Interval 31.5 to 53.5

SECONDARY outcome

Timeframe: From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 25.7 months)

Population: ITT population: Participants who were randomized on the study (eligible and ineligible).

PFS is defined as time interval from the date of randomization to the date of (first) progression or date of death. Participants who progressed or died were counted as events. Participants lost to follow-up were censored as of the last date of contact. Participants who started a new treatment before they progressed were censored as of the date of start of the new treatment. Participants who had not progressed or died were censored at the date of last follow-up. PFS (months) = (End date - date of randomization + 1)/30.4375.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=85 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=91 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Median Progression Free Survival	2.9 Months Interval 2.7 to 5.1	5.3 Months Interval 3.8 to 6.2

SECONDARY outcome

Timeframe: Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months)

Population: Evaluable population-All treated participants with CR, PR, stable disease (SD), progressive disease (PD), or nonevaluable (NE) response and who had received at least 1 dose of study drug. Please refer outcome measure 4 for explanation of SD, PD, and NE.

ORR is defined as the proportion of responders (complete response \[CR\] + partial response \[PR\] in participants with measurable disease) in that arm among all randomized participants. CR: Disappearance of all evidence of target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. Measurable disease: Lesions that can be accurately measured in at least one dimension (LD to be recorded) as ≥20 mm with conventional techniques (computed tomography \[CT\], magnetic resonance imaging \[MRI\], X-ray) or as ≥10 mm with spiral CT scan.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=79 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=89 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Overall Response Rate (ORR) Based on Response Criteria in Solid Tumors [RECIST]	7.6 Percentage of Participants Interval 2.8 to 15.8	13.5 Percentage of Participants Interval 7.2 to 22.4

SECONDARY outcome

Timeframe: Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months)

Population: Evaluable population: All treated participants with CR, PR, SD, PD, or NE response and who had received at least 1 dose of study drug.

Determined based on the sequence of disease status with corresponding best response. PD=At least a 20% increase in the sum of LD of target lesions in reference to the smallest sum LD recorded or the appearance of 1 or more new lesions; SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD in reference to the smallest sum LD. NE=Participants who discontinued treatment secondary to toxicity or died (either before completion of 1 treatment cycle). Please refer outcome measure 3 for explanation of CR and PR. CR+PR+SD=overall disease control.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=79 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=89 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Best Response as Assessed With RECIST CR	0 Percentage of Participants No participants had CR.	1.1 Percentage of Participants Interval 0.0 to 6.1
Best Response as Assessed With RECIST PR	7.6 Percentage of Participants Interval 2.8 to 15.8	12.4 Percentage of Participants Interval 6.3 to 21.0
Best Response as Assessed With RECIST SD	40.5 Percentage of Participants Interval 29.6 to 52.1	44.9 Percentage of Participants Interval 34.4 to 55.9
Best Response as Assessed With RECIST SD>=6 months	19.0 Percentage of Participants Interval 11.0 to 29.4	15.7 Percentage of Participants Interval 8.9 to 25.0
Best Response as Assessed With RECIST PD	41.8 Percentage of Participants Interval 30.8 to 53.4	29.2 Percentage of Participants Interval 20.1 to 39.8
Best Response as Assessed With RECIST NE	10.1 Percentage of Participants Interval 4.5 to 19.0	12.4 Percentage of Participants Interval 6.3 to 21.0
Best Response as Assessed With RECIST CR+PR+SD>=6 mos	26.6 Percentage of Participants Interval 17.3 to 37.7	29.2 Percentage of Participants Interval 20.1 to 39.8

SECONDARY outcome

Timeframe: From the date of randomization to date of death (maximum participant OS of 26.3 months)

Population: ITT population: Participants who were randomized on the study (eligible and ineligible).

Survival was measured as the date of randomization to the date of death. Participants who were alive at the time of the database lock or lost to follow-up were censored at the last known alive date. The distribution of overall survival was analyzed via the Kaplan Meier method in each arm. Survival time (months) = (End date - date of randomization + 1)/30.4375

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=85 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=91 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Overall Survival (OS)	13.9 Months Interval 12.1 to 15.7	16.1 Months Interval 10.3 to Insufficient number of participants with an event were available to estimate the upper limit of the confidence interval.

SECONDARY outcome

Timeframe: From the date of first dose to date of first PR or CR assessment ( maximum participant time to response of 8.3 months)

Population: ITT population with CR or PR.

Time to response is defined as the time from the start of treatment until the first (confirmed) CR or PR was recorded. Time to response was computed only for participants whose best response was PR or CR. CR: Disappearance of all target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions with reference to the baseline sum LD.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=6 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=12 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Time to Response	2.5 Months Interval 1.7 to 8.3	2.8 Months Interval 2.0 to 8.1

SECONDARY outcome

Timeframe: From the date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 17.4 months)

Population: ITT population with CR or PR.

Duration of overall response was defined as the period from the time first PR or CR was recorded until the first date of documented PD or death. Duration of response was computed for participants whose best response was either PR or CR. Participants who neither relapsed nor died were censored on the date of their last tumor assessment. Kaplan-Meier method was used to estimate the duration of response. Refer to outcome measures 3 and 4 for CR, PR, and PD.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=6 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=12 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Duration of Response	6.2 Months Interval 3.3 to Insufficient number of participants with an event were available to estimate the upper limit of the confidence interval.	6.3 Months Interval 4.1 to 17.3

SECONDARY outcome

Timeframe: Assessed from the date of first study dose until at least 30 days after the last dose of study drug. Median time on study therapy was 12 weeks (range: 4-60 weeks for 16 mg/m^2 arm; 3-87 weeks for 40 mg/m^2 arm).

Population: Safety population.

All events of peripheral neuropathy were assessed and graded per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3. CTC Grade (GR) 1=Mild; GR2=Moderate; GR3=Severe or medically significant, not immediately life-threatening; and GR4=Life-threatening. All treatment-related and not related Neuropathy and Peripheral Neuropathy were included; serious adverse events (SAEs) were not included.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=82 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=89 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Incidence of All Grades of Peripheral Neuropathy All	26 Participants	39 Participants
Incidence of All Grades of Peripheral Neuropathy Grade 1	9 Participants	15 Participants
Incidence of All Grades of Peripheral Neuropathy Grade 2	10 Participants	10 Participants
Incidence of All Grades of Peripheral Neuropathy Grade 3	6 Participants	14 Participants
Incidence of All Grades of Peripheral Neuropathy Grade 4	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on study therapy was 12 weeks (range: 4-60 weeks for 16 mg/m^2 arm; 3-87 weeks for 40 mg/m^2 arm).

Population: ITT population: Participants randomized on the study (eligible and ineligible). AEs, AEs leading to death and GR 3-4 AEs: Safety population-Participants who received atleast 1 dose of study drug). AEs leading to death: For 4 participants in Arm 1 and both participants in Arm 2, the reported AE term was "disease progression."

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. GR=Grade.

Outcome measures

Outcome measures
Measure	Ixabepilone 16 mg/m^2 n=85 Participants ixabepilone 16 mg/m\^2 weekly for 3 weeks followed by 1 week rest	Ixabepilone 40 mg/m^2 n=91 Participants ixabepilone 40 mg/m\^2 every 3 weeks
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia GR 1 and 2 drug-related neutropenia	10 Participants	13 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia GR 3 drug-related neutropenia	3 Participants	18 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia GR 4 drug-related neutropenia	2 Participants	16 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia Drug-related alopecia (All)	21 Participants	54 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia GR 1 and 2 drug-related alopecia	21 Participants	54 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia Deaths (All)	55 Participants	48 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia Treatment-related deaths	0 Participants	0 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia AEs leading to death (n=82; n=89)	7 Participants	2 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia At least 1 SAE	25 Participants	30 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia At least 1 study-related SAE	5 Participants	17 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia AEs leading to discontinuation	15 Participants	30 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia At least 1 AE (n=82; n=89)	82 Participants	89 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia At least 1 study-related AEs	69 Participants	84 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia At least 1 GR 3 and 4 AEs (n=82; n=89)	34 Participants	69 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia At least 1 study-related GR 3 and 4 AEs	23 Participants	61 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia Drug-related peripheral neuropathy (All)	26 Participants	38 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia GR 1 and 2 drug-related peripheral neuropathy	19 Participants	24 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia GR 3 drug-related peripheral neuropathy	6 Participants	14 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia GR 4 drug-related peripheral neuropathy	1 Participants	0 Participants
Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia Drug-related neutropenia (All)	15 Participants	47 Participants

Adverse Events

Ixabepilone 16 mg/m^2

Serious events: 25 serious events

Other events: 82 other events

Deaths: 0 deaths

Ixabepilone 40 mg/m^2

Serious events: 30 serious events

Other events: 89 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 ≤60 days 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