Study to Assess Effectiveness of Giving Combination of St... | NCT00455533

ID	Type	Description	Link
EUDRACT 2006-003047-24

Label	Type	Description	Intervention Names
A	Experimental		Drug: Ixabepilone Drug: Cyclophosphamide Drug: Doxorubicin
B	Active Comparator		Drug: Paclitaxel Drug: Cyclophosphamide Drug: Doxorubicin

Name	Type	Description	Arm Group Labels	Other Names
Ixabepilone	Drug	Intravenous Solution, intravenous (IV), 40mg/m², Day 1 every 21 days, 12 Weeks	A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving Pathologic Complete Response (pCR)	The pCR was defined as no histologic evidence of residual invasive adenocarcinoma in the breast and axillary lymph nodes, with or without the presence of ductal carcinoma in situ (DCIS) in the breast.	at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
Percentage of Participants Achieving Pathologic Complete Response (pCR) in Biomarker-Defined Populations	Beta III tubulin positivity determined by cross-validation method. Optimal cutoff: ≥46% tumor cells staining at 2 plus or 3 plus intensity (corresponding Beta III tubulin positivity=39.4%). Pre-specified cutoff of Beta III tubulin positivity: ≥50% 2plus or 3plus cells (corresponding prevalence=38.5%). Optimal cutoffs for TACC3 and CAPG positivity determined by cross-validation method: 6.889 and 6.844 [log2 normalized intensity units], respectively (corresponding to prevalence rates of 43.3% and 44.3%).	pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.
Percentage of Participants Achieving Pathologic Complete Response (pCR) in 20- and 26-Gene Model Subgroups	For each of the 2 biomarker sets (20-gene or 26-gene), a multi-gene model was built using penalized logistic regression on all pharmacogenomic evaluable subjects for each treatment arm separately. Receiver Operating Characteristic (ROC) plots for separate arm using 5 fold cross validation were generated. ROC for separate arms using cross over were also added. Further analysis on the multiple gene models (as mentioned in the SAP) was planned only based on the initial findings from the 2 ROC plots. For 20- and 26-gene models, ROC curves generated for each study arm did not indicate that these multi-gene models differentially predicted for pCR between the treatment arms, so further analyses to estimate the optimal cut-off and the pCR rates were not conducted.	pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving Clinical Objective Response	Clinical response was defined as the number of participants who achieved modified World Health Organization's tumor response criteria of clinical complete response (complete disappearance of all clinically palpable detectable malignant disease and/or disappearance of radiological evidence of tumor in the breast and ipsilateral axillary lymph nodes) or clinical partial response (clinical evidence of a reduction in total tumor size of >= 50% in the overall sum of the products of diameters of breast and axillary lesions), divided by the number of randomized participants in that arm.

Eligibility Module

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Comprehensive Cancer Center		Palm Springs	California	92262	United States
Northwest Oncology & Hematology Associates

PubMed Identifier	Type	Citation	Retractions
27312051	Derived	Abdel-Fatah TMA, Agarwal D, Liu DX, Russell R, Rueda OM, Liu K, Xu B, Moseley PM, Green AR, Pockley AG, Rees RC, Caldas C, Ellis IO, Ball GR, Chan SYT. SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated genomic, transcriptomic, and protein analysis. Lancet Oncol. 2016 Jul;17(7):1004-1018. doi: 10.1016/S1470-2045(16)00174-1. Epub 2016 Jun 14.

ID	Title	Description
FG000	Doxorubicin / Cyclophosphamide (AC)	60 mg/m^2 doxorubicin and 600 mg/m^2 cyclophosphamide (AC) every 3 weeks for 4 cycles (12 weeks).
FG001	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Achieving Pathologic Complete Response (pCR)

The pCR was defined as no histologic evidence of residual invasive adenocarcinoma in the breast and axillary lymph nodes, with or without the presence of ductal carcinoma in situ (DCIS) in the breast.

All randomized participants

Posted

Number

90% Confidence Interval

Percentage of Participants

at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000148 OG001147

Title

Denominators

Categories

Title	Measurements
	OG00024.3(18.6 to 30.8) OG00125.2(19.4 to 31.7)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		0.8921							95						No	Superiority or Other
OG000 OG001		Cochran-Mantel-Haenszel		0.8966

Secondary

Percentage of Participants Achieving Clinical Objective Response

Clinical response was defined as the number of participants who achieved modified World Health Organization's tumor response criteria of clinical complete response (complete disappearance of all clinically palpable detectable malignant disease and/or disappearance of radiological evidence of tumor in the breast and ipsilateral axillary lymph nodes) or clinical partial response (clinical evidence of a reduction in total tumor size of >= 50% in the overall sum of the products of diameters of breast and axillary lesions), divided by the number of randomized participants in that arm.

All randomized participants

Posted

Number

90% Confidence Interval

Percentage of Participants

after the last dose of either ixabepilone or paclitaxel (at 12 weeks) but before surgery (4-6 weeks after the last dose of 12 weeks of therapy)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts

Secondary

Percentage of Participants Requiring Breast Conservation Surgery

Number of randomized participants requiring breast conservation surgery following study treatment.

All randomized participants

Posted

Number

90% Confidence Interval

Percentage of Participants

at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Achieving Combined pCR and Minimal Residual Cancer Burden (RCB) 1

Combined pCR and RCB-1 was defined as participants with no histologic evidence of residual invasive adenocarcinoma in the breast and axillary lymph nodes, with or without the presence of DCIS in the breast plus subjects with RCB-1 following the RCB calculation based on data entered by the investigator sites in each arm.

All randomized participants

Posted

Number

90% Confidence Interval

Percentage of Participants

at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Secondary

Randomized Participants With Non-missing pCR & Biomarker Expression (GENE [Probe Set]), to Explore Whether Gene Expression Patterns for GTSE1, Isoforms of β-tubulin, Kallikreins 5, 6, 10 Are Differentially Predictive of pCR

Relevance of biomarker in differentiation between ixabepilone & paclitaxel evaluated by logistic regression with pCR as response. Statistical analyses include: 1) the likelihood ratio test between the full model (PCR~Biomarker:Treatment:estrogen receptor [ER]) & reduced model (PCR~Treatment:ER); 2) the likelihood ratio test between the full model (PCR~Biomarker:Treatment) & reduced model (PCR~Biomarker+Treatment); 3) the contrast of the interaction between treatment & biomarker expression within ER Negative subjects from the full model(PCR~Biomarker:Treatment:ER). A:B represents A,B & A*B.

Posted

Number

participants

pCR evaluated at time of surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

ID	Title	Description
OG000	Randomized Participants

Units	Counts
Participants	OG000

Secondary

Randomized Participants With Non-missing pCR & Biomarker Expression (GENE [Probe Set]) to Explore Whether Gene Expression Patterns for GTSE1, Isoforms of β-tubulin, Kallikreins 5, 6, 10 Are Differentially Predictive of pCR/RCB1

Relevance of biomarker in differentiation between ixabepilone & paclitaxel evaluated by logistic regression with pCR/RCB1 as response. Statistical analyses include: 1) likelihood ratio test between the full model (pCR/RCB1~Biomarker:Treatment: ER) & reduced model (pCR/RCB1~Treatment:ER); 2) likelihood ratio test between the full model (pCR/RCB1 Biomarker:Treatment) & reduced model (pCR/RCB1~Biomarker+Treatment); 3) contrast of the interaction between treatment & biomarker expression within ER Negative subjects from the full model (pCR/RCB1~Biomarker:Treatment:ER). A:B represents A,B & A*B.

Posted

Number

participants

pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

ID	Title	Description
OG000	Randomized Participants

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-Specified Thresholds

Percentage of participants with pCR in MDR1 IHC positive and negative groups using 2 pre-specified thresholds,. The first pre-specified threshold for MDR1-positivity (Mem) =Any membrane staining. The second pre-specified threshold for MDR1-positivity (Mem+Cyto)=Any membrane staining or at least 200 Cytoplasmic H-score.

Randomized participants with non-missing pCR and biomarker expression

Posted

Number

90% Confidence Interval

percentage of participants

: pCR evaluated at time of surgery (4-6 weeks after the last dose of 12 weeks of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With pCR/RCB1 and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds

Percentage of participants with pCR/RCB1 in MDR1 IHC positive and negative groups using 2 pre-specified thresholds,. The first pre-specified threshold for MDR1-positivity (Mem) =Any membrane staining. The second pre-specified threshold for MDR1-positivity (Mem+Cyto)=Any membrane staining or at least 200 Cytoplasmic H-score .

Randomized participants with non-missing pCR/RCB1 and biomarker expression

Posted

Number

90% Confidence Interval

percentage of participants

pCR evaluated at time of surgery (4-6 weeks after the last dose of 12 weeks of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds, Estrogen-Receptor (ER) Negative Participants

Percentage of ER negative participants with pCR and MDR1 immunohistochemistry (IHC) positivity using 2 pre-specified thresholds, stratified by biomarker status. The first pre-specified threshold for MDR1-positivity (Mem)=Any membrane staining. The second pre-specified threshold for MDR1-positivity (Mem+Cyto)=Any membrane staining or at least 200 Cytoplasmic H-score.

Randomized estrogen negative participants with non-missing pCR and biomarker expression

Posted

Number

90% Confidence Interval

percentage of participants

pCR evaluated at time of surgery (4-6 weeks after the last dose of 12 weeks of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants

Secondary

Prevalence of Biomarker Based on Optimal Threshold (Biomarker Positive Participants)

Percentage of participants having the following optimal biomarker thresholds as computed from the cross-validation method (cutoff of biomarker positive [with 90% confidence interval by Bootstrap method]): Beta 3 Tubulin IHC (45.866 [5, 83.9]); TACC3 mRNA (6.714 [6.312, 7.192]); CAPG mRNA (6.739 [5.728, 7.298]). Optimal thresholds for a 20-gene model and a 26-gene model were also planned; however, these were not determined because preliminary analyses did not indicate that they would not differentiate pCR rates between treatment arm.

Randomized participants with non-missing pCR and biomarker expressions. n=the number of participants with specific biomarker expression.

Posted

Number

90% Confidence Interval

Percentage of Participants

pCR evaluated at time of surgery (4-6 weeks after the last dose of 12 weeks of therapy); mandatory tumor tissue biopsy and mRNA samples obtained prior to treatment

ID	Title	Description
OG000	Randomized Participants	Randomized Participants with non-missing pCR and biomarker expression

Units	Counts
Participants	OG000

Secondary

Overall Safety Summary: Deaths, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Drug-Related AEs, and Most Common Treatment-Related Non-Hematologic Adverse Events (TNAEs) Occuring in >=10% of Participants

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. By Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grades

Posted

Number

Participants

prior to the first study treatment, at the beginning of each subsequent cycle, weekly during the treatment period and a minimum of 4 weeks after the last dose of 12 weeks of study therapy

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Secondary

Severity of Any Drug-Related AEs and Gastrointestinal AEs by System Organ Class

MCT=musculoskeletal and connective tissue, GDASC=general disorders and administration site conditions, RTM=respiratory, thoracic and mediastinal disorders, NBMUCP=neoplasms benign, malignant and unspecified (including cysts and polyps). Drug related adverse events are those events with relationship to study therapy of certain, probable, possible or missing. Subjects may have more than one event within a class. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

Ixabepilone- and Paclitaxel-treated participants

Posted

Number

Participants

prior to the first study treatment, at the beginning of each subsequent cycle, weekly during the treatment period and a minimum of 4 weeks after the last dose of 12 weeks of study therapy

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts

Secondary

On-Study Hematology: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

Ixabepilone/Paclitaxel treated participants for whom on-study labs were recorded.

Posted

Number

Participants

prior to the first study treatment, at the beginning of each subsequent cycle, weekly during the treatment period and a minimum of 4 weeks after the last dose of 12 weeks of study therapy during ixabepilone or paclitaxel treatment phase

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts

Primary

Percentage of Participants Achieving Pathologic Complete Response (pCR) in Biomarker-Defined Populations

Beta III tubulin positivity determined by cross-validation method. Optimal cutoff: ≥46% tumor cells staining at 2 plus or 3 plus intensity (corresponding Beta III tubulin positivity=39.4%). Pre-specified cutoff of Beta III tubulin positivity: ≥50% 2plus or 3plus cells (corresponding prevalence=38.5%). Optimal cutoffs for TACC3 and CAPG positivity determined by cross-validation method: 6.889 and 6.844 [log2 normalized intensity units], respectively (corresponding to prevalence rates of 43.3% and 44.3%).

For all subgroups other than Beta-III positive/negative subgroup based on a pre-determined cutoff, results were estimated using a cross-validation method (a resampling based technique, making individual sample size [N] not applicable).

Posted

Number

90% Confidence Interval

Percentage of Participants

pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Secondary

On-Study Liver Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase

Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST). AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

Ixabepilone/Paclitaxel treated participants for whom on-study labs were recorded; n=number of participants with specific laboratory evaluation.

Posted

Number

Participants

prior to the first study treatment, at the beginning of each subsequent cycle, weekly during the treatment period and a minimum of 4 weeks after the last dose of study therapy during ixabepilone or paclitaxel treatment phase

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Secondary

On-Study Renal Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

Ixabepilone/Paclitaxel treated participants for whom on-study labs were recorded.

Posted

Number

Participants

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts

Secondary

Number of Participants by Dose for AC

ixabepilone- and paclitaxel-treated participants

Posted

Number

participants

12 weeks (4 3-week cycles)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Secondary

Number of Participants by Dose for Ixabepilone/Paclitaxel

ixabepilone- and paclitaxel-treated participants

Posted

Number

participants

12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Secondary

Reason for First Dose Reduction of AC

ixabepilone- and paclitaxel-treated participants with at least 2 courses of AC

Posted

Number

participants

12 weeks (4 3-week cycles)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Secondary

Reason for First Dose Reduction of Ixabepilone/Paclitaxel

ixabepilone- and paclitaxel-treated participants with at least 2 courses of Ixabepilone/Paclitaxel

Posted

Number

participants

12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Secondary

Number of Participants With Course Delay and Reason for Delay for AC

ixabepilone- and paclitaxel-treated participants with at least 2 courses of AC

Posted

Number

participants

12 weeks (4 3-week cycles)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Secondary

Number of Participants With Dose Delay and Reason for Dose Delay for Ixabepilone/Paclitaxel

ixabepilone- and paclitaxel-treated participants with at least 2 courses of Ixabepilone/Paclitaxel

Posted

Number

participants

12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Units	Counts
Participants	OG000

Primary

Percentage of Participants Achieving Pathologic Complete Response (pCR) in 20- and 26-Gene Model Subgroups

For each of the 2 biomarker sets (20-gene or 26-gene), a multi-gene model was built using penalized logistic regression on all pharmacogenomic evaluable subjects for each treatment arm separately. Receiver Operating Characteristic (ROC) plots for separate arm using 5 fold cross validation were generated. ROC for separate arms using cross over were also added. Further analysis on the multiple gene models (as mentioned in the SAP) was planned only based on the initial findings from the 2 ROC plots. For 20- and 26-gene models, ROC curves generated for each study arm did not indicate that these multi-gene models differentially predicted for pCR between the treatment arms, so further analyses to estimate the optimal cut-off and the pCR rates were not conducted.

For 20- and 26-gene models, ROC curves generated for each study arm did not indicate that these multi-gene models differentially predicted for pCR between the treatment arms, so further analyses to estimate the optimal cut-off and the pCR rates were not conducted.

Posted

pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.

ID	Title	Description
OG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
OG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
HAEMOGLOBIN DECREASED	Investigations	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
CARDIAC FAILURE	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
CARDIO-RESPIRATORY ARREST	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
HYPOTENSION	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected144 at risk
PERIPHERAL ISCHAEMIA	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
HYPERBILIRUBINAEMIA	Hepatobiliary disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
ANAPHYLACTIC SHOCK	Immune system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
ANAPHYLACTIC REACTION	Immune system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
HEADACHE	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
SOMNOLENCE	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
ENCEPHALOPATHY	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
CRANIAL NEUROPATHY	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
NEUROPATHY PERIPHERAL	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
CEREBRAL VENOUS THROMBOSIS	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected145 at risk EG0011 affected144 at risk
DEPRESSED LEVEL OF CONSCIOUSNESS	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
VOMITING	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected145 at risk EG0010 affected144 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0004 affected145 at risk EG0010 affected144 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
GALLSTONE ILEUS	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
SEPSIS	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
PNEUMONIA	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected144 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
HYPOALBUMINAEMIA	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
ANAEMIA	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected145 at risk EG0010 affected144 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
LEUKOCYTOSIS	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected144 at risk
THROMBOTIC THROMBOCYTOPENIC PURPURA	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
DISSEMINATED INTRAVASCULAR COAGULATION	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
URTICARIA	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
EXFOLIATIVE RASH	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
OVERDOSE	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0003 affected145 at risk EG0010 affected144 at risk
MEDICATION ERROR	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
LOWER LIMB FRACTURE	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected144 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected144 at risk
ASTHMA	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
HYPOXIA	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0013 affected144 at risk
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected144 at risk
NON-CARDIOGENIC PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
ACUTE RESPIRATORY DISTRESS SYNDROME	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
FATIGUE	General disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected145 at risk EG0011 affected144 at risk
PYREXIA	General disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0013 affected144 at risk
SUDDEN DEATH	General disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected144 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 12.1	Systematic Assessment	EG0008 affected145 at risk EG00112 affected144 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 12.1	Systematic Assessment	EG0004 affected145 at risk EG0019 affected144 at risk
HOT FLUSH	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0008 affected145 at risk EG00112 affected144 at risk
INSOMNIA	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG00016 affected145 at risk EG00117 affected144 at risk
HEADACHE	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0006 affected145 at risk EG0019 affected144 at risk
DYSGEUSIA	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected145 at risk EG0018 affected144 at risk
PARAESTHESIA	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG00010 affected145 at risk EG0014 affected144 at risk
NEUROPATHY PERIPHERAL	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG00024 affected145 at risk EG00123 affected144 at risk
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG00027 affected145 at risk EG00144 affected144 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG00027 affected145 at risk EG00118 affected144 at risk
VOMITING	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG00014 affected145 at risk EG0015 affected144 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG00024 affected145 at risk EG00119 affected144 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0006 affected145 at risk EG00111 affected144 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0009 affected145 at risk EG0019 affected144 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG00012 affected145 at risk EG0019 affected144 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG00028 affected145 at risk EG00115 affected144 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG00013 affected145 at risk EG00116 affected144 at risk
ALOPECIA	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0004 affected145 at risk EG0019 affected144 at risk
NAIL DISORDER	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0007 affected145 at risk EG00112 affected144 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG00043 affected145 at risk EG00118 affected144 at risk
BONE PAIN	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG00030 affected145 at risk EG0016 affected144 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG00034 affected145 at risk EG00115 affected144 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0008 affected145 at risk EG0017 affected144 at risk
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG00016 affected145 at risk EG0017 affected144 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0007 affected145 at risk EG00119 affected144 at risk
PAIN	General disorders	MedDRA 12.1	Systematic Assessment	EG00010 affected145 at risk EG0018 affected144 at risk
FATIGUE	General disorders	MedDRA 12.1	Systematic Assessment	EG00027 affected145 at risk EG00124 affected144 at risk
PYREXIA	General disorders	MedDRA 12.1	Systematic Assessment	EG0006 affected145 at risk EG00110 affected144 at risk
ASTHENIA	General disorders	MedDRA 12.1	Systematic Assessment	EG00013 affected145 at risk EG00110 affected144 at risk
MUCOSAL INFLAMMATION	General disorders	MedDRA 12.1	Systematic Assessment	EG0009 affected145 at risk EG0012 affected144 at risk

ID	Title	Description
BG000	Ixabepilone (Randomized Population)	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)
BG001	Paclitaxel (Randomized Population)	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks
BG002	Total	Total of all reporting groups

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D018942	Macrolides
D061065	Polyketides
D007783	Lactones
D009930	Organic Chemicals
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ixabepilone	ixabepilone 40 mg/m^2 administered intravenously (IV) over 3 hours, every 3 weeks for 4 cycles (12 weeks)			17	145	128	145
EG001	Paclitaxel	paclitaxel 80 mg/m^2 administered IV every week for 12 weeks			11	144	117	144

ID	Term
C430592	ixabepilone
D034261	Epothilones
D017239	Paclitaxel
D003520	Cyclophosphamide
D004317	Doxorubicin