Trial Outcomes & Findings for A Phase II Combination of Trastuzumab and Ixabepilone Versus Trastuzumab and Docetaxel in Patients With Advanced and/or Metastatic Breast Cancer (NCT NCT00490646)

Last Updated: 2016-03-10

Results Overview

Percentage of participants with best overall response (BOR) of either complete response (CR) or partial response (PR) according to RECIST version 1.1 as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A two-sided confidence interval (CI) was computed using the Clopper-Pearson method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)

Results posted on

2016-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Overall Study STARTED	25	25
Overall Study Treated	24	24
Overall Study COMPLETED	23	23
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Overall Study Still on trastuzumab monotherapy	1	1
Overall Study Never Treated (had an adverse event)	1	0
Overall Study Never Treated (withdrew consent)	0	1

Baseline Characteristics

A Phase II Combination of Trastuzumab and Ixabepilone Versus Trastuzumab and Docetaxel in Patients With Advanced and/or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Total n=50 Participants Total of all reporting groups
Age, Continuous	52.0 years n=5 Participants	53.0 years n=7 Participants	52.5 years n=5 Participants
Age, Customized < 65 years	19 participants n=5 Participants	21 participants n=7 Participants	40 participants n=5 Participants
Age, Customized >=65 years	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Sex/Gender, Customized Female	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants
Race/Ethnicity, Customized White	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants
Karnofsky Performance Status 100	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
Karnofsky Performance Status 90	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Karnofsky Performance Status 80	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
Karnofsky Performance Status 70	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Karnofsky Performance Status Not Reported	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Menopausal Status Pre-menopausal	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Menopausal Status Peri-menopausal	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Menopausal Status Post-menopausal	14 participants n=5 Participants	15 participants n=7 Participants	29 participants n=5 Participants
Menopausal Status Not Reported	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Number of participants who received prior chemotherapy in neoadjuvant/adjuvant setting	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)

Population: All randomized participants.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1)	60.0 percentage of participants Interval 38.7 to 78.9	52.0 percentage of participants Interval 31.3 to 72.2

PRIMARY outcome

Timeframe: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).

Population: All randomized participants.

BOR was the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. Refer to Outcome Measure 3 for definition of PD.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Complete response	3 participants	2 participants
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Partial response	12 participants	11 participants
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Stable disease	6 participants	9 participants
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Progressive disease	1 participants	1 participants
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Unable to determine (UTD; Death due to toxicity)	1 participants	0 participants
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 UTD (reason other than toxicity or progression)	1 participants	1 participants
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Never treated	1 participants	1 participants

SECONDARY outcome

Timeframe: From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).

Population: All randomized participants. Participants who did not progress or died were censored on the date of their last tumor assessment.

Time in months from randomization until first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=25 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Progression Free Survival (PFS)	11.3 months Interval 5.8 to 16.8	13.0 months Interval 6.7 to 21.6

SECONDARY outcome

Timeframe: From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)

Population: All randomized participants with CR or PR.

Time to response was defined as the time in weeks from randomization until the measurement criteria are first met for a CR or PR, whichever is recorded first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=15 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=13 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Time to Response	10.1 weeks Interval 5.9 to 18.4	7.3 weeks Interval 5.0 to 18.1

SECONDARY outcome

Timeframe: From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)

Population: All randomized participants with CR or PR. The participants who neither relapsed nor died were censored on the date of their last tumor assessment.

Period measured in months from time that measurement criteria were first met for CR or PR until first date of documented PD or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Refer to Outcome Measure 1 for definitions of CR and PR. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by Brookmeyer and Crowley method.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=15 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=13 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Duration of Response	11.5 months Interval 6.8 to 21.4	16.5 months Interval 7.2 to Data insufficient to estimate the upper limit of the confidence interval.

SECONDARY outcome

Timeframe: Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)

Population: Treated participants: Participants who received at least 1 dose of study therapy.

AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 3=Severe; and Grade 4=Life-threatening or disabling. GR=Grade.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=24 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=24 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 All deaths	1 participants	1 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 Death within 30 days of last dose of study therapy	1 participants	0 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 SAEs (Any Grade)	6 participants	13 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 SAEs (Grades 3-4)	4 participants	12 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 Drug-related SAEs (Any Grade)	3 participants	10 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 Drug-related SAEs (Grades 3-4)	2 participants	8 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 AEs (Any Grade)	24 participants	24 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 AEs (Grades 3-4)	19 participants	23 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 Drug-related AEs (Any Grade)	24 participants	24 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 Drug-related AEs (Grades 3-4)	18 participants	22 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 AEs leading to discontinuation of therapy (Any GR)	5 participants	9 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 AEs leading to discontinuation of therapy (GR 3-4)	2 participants	4 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 Drug-related peripheral neuropathy (Any Grade)	16 participants	12 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 Drug-related peripheral neuropathy (Grades 3-4)	2 participants	0 participants

SECONDARY outcome

Timeframe: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)

Population: Treated participants: Participants who received at least 1 dose of study therapy. n=number of participants with measures available.

Grade (GR)1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=\<LLN-3.0\*10\^9/L; GR2=\<3.0-2.0\*10\^9/L; GR3=\<2.0-1.0\*10\^9/L; GR4=\<1.0\*10\^9/L. Absolute Neutrophil Count (ANC):GR1=\<LLN-1.5\*10\^9 /L; GR2=\<1.5-1.0\*10\^9/L; GR3=\<1.0-0.5\*10\^9/L; GR4=\<0.5\*10\^9/L. Platelets:GR1=\<LLN-75.0\*10\^9/L; GR2=\<75.0-50.0\*10\^9/L; GR3=\<50.0-25.0\*10\^9/L, GR4=\<25.0\*10\^9/L. Hemoglobin:GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3=\<8.0-6.5g/dL, GR4=\<6.5g/dL. LLN=lower limit of normal.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=24 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=24 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 WBC Grade 1 (n=24; n=22)	6 participants	1 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 WBC Grade 2 (n=24; n=22)	7 participants	1 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 WBC Grade 3 (n=24; n=22)	8 participants	15 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 WBC Grade 4 (n=24; n=22)	1 participants	4 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ANC Grade 1 (n=23; n=23)	2 participants	0 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ANC Grade 2 (n=23; n=23)	4 participants	0 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ANC Grade 3 (n=23; n=23)	8 participants	3 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ANC Grade 4 (n=23; n=23)	6 participants	19 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Platelet Count Grade 1 (n=24; n=23)	9 participants	3 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Platelet Count Grade 2 (n=24; n=23)	0 participants	0 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Platelet Count Grade 3 (n=24; n=23)	0 participants	0 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Platelet Count Grade 4 (n=24; n=23)	1 participants	0 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Hemoglobin Grade 1 (n=24; n=23)	14 participants	12 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Hemoglobin Grade 2 (n=24; n=23)	8 participants	8 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Hemoglobin Grade 3 (n=24; n=23)	0 participants	1 participants
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Hemoglobin Grade 4 (n=24; n=23)	0 participants	0 participants

SECONDARY outcome

Timeframe: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)

Population: Treated participants: Participants who received at least 1 dose of study therapy. n=number of participants with measures available.

Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=\>ULN-2.5\*ULN; GR2=\>2.5-5.0\*ULN; GR3=\>5.0-20.0\*ULN; GR4=\>20.0\*ULN. Total bilirubin: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3-10\*ULN, GR4=\>10\*ULN. Creatinine: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3.0-6.0\*ULN, GR4=\>6.0\*ULN. ULN=upper limit of normal.

Outcome measures

Outcome measures
Measure	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=24 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=24 Participants trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALP Grade 1 (n=23; n=23)	11 participants	8 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALP Grade 2 (n=23; n=23)	0 participants	1 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALP Grade 3 (n=23; n=23)	0 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALP Grade 4 (n=23; n=23)	0 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALT Grade 1 (n=24; n=23)	10 participants	15 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALT Grade 2 (n=24; n=23)	3 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALT Grade 3 (n=24; n=23)	0 participants	1 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 ALT Grade 4 (n=24; n=23)	0 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 AST Grade 1 (n=24; n=23)	13 participants	11 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 AST Grade 2 (n=24; n=23)	0 participants	1 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 AST Grade 3 (n=24; n=23)	1 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 AST Grade 4 (n=24; n=23)	0 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Total Bilirubin Grade 1 (n=24; n=23)	2 participants	2 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Total Bilirubin Grade 2 (n=24; n=23)	0 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Total Bilirubin Grade 3 (n=24; n=23)	1 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Total Bilirubin Grade 4 (n=24; n=23)	0 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Creatinine Grade 1 (n=24; n=23)	2 participants	1 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Creatinine Grade 2 (n=24; n=23)	2 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Creatinine Grade 3 (n=24; n=23)	0 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 Creatinine Grade 4 (n=24; n=23)	0 participants	0 participants

Adverse Events

Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV

Serious events: 13 serious events

Other events: 23 other events

Deaths: 0 deaths

Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV

Serious events: 6 serious events

Other events: 24 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

Measure	Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV n=24 participants at risk trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.	Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV n=24 participants at risk trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Vascular disorders CIRCULATORY COLLAPSE	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Nervous system disorders ATAXIA	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Cardiac disorders PERICARDIAL EFFUSION	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	20.8% 5/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Blood and lymphatic system disorders HAEMATOTOXICITY	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Musculoskeletal and connective tissue disorders PATHOLOGICAL FRACTURE	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
General disorders PYREXIA	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Congenital, familial and genetic disorders APLASIA	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Cardiac disorders ATRIAL FIBRILLATION	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Vascular disorders HYPERTENSION	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Gastrointestinal disorders NAUSEA	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Blood and lymphatic system disorders NEUTROPENIA	12.5% 3/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Respiratory, thoracic and mediastinal disorders DYSPNOEA	8.3% 2/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
General disorders EXTRAVASATION	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Hepatobiliary disorders CHOLECYSTITIS	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Blood and lymphatic system disorders LYMPHADENOPATHY	0.00% 0/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)	4.2% 1/24 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)