Breast CancerPhase 2NCT00455533
Study to Assess Effectiveness of Giving Combination of Standard Chemotherapy Drugs Versus Combination of Standard Chemotherapy and New Drug Ixabepilone When Given Before Surgical Removal of Early Stage Breast Cancer
A Phase 2 study testing Ixabepilone, Paclitaxel and Cyclophosphamide in people with Breast Cancer, run by Bristol-Myers Squibb at 49 sites in 15 countries.
Trial summary
The study will evaluate the effectiveness of ixabepilone when given after doxorubicin plus cyclophosphamide (AC) compared to standard treatment of paclitaxel given after doxorubicin plus cyclophosphamide in patients with early stage breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Ixabepilone, Paclitaxel and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 384 participants
- Where
- 49 sitesin 15 countries
- Study dates
- Oct 2007to Dec 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed primary invasive adenocarcinoma of the breast , T2-3, N0-3, M0, with tumor size of ≥ 2 cm
- All patients with early stage breast adenocarcinoma may enroll irrespective of receptor status
- No prior treatment for breast cancer excluding therapy for DCIS
- Karnofsky performance status of 80 - 100
- left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or multiple gated acquisition (MUGA)
- Adequate hematologic, hepatic and renal function
Who cannot join
- women of child-bearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy during and up to 8 weeks after the last dose of the investigational drug
- Women who are pregnant or breastfeeding
- Inflammatory or metastatic breast cancer
- Unfit for breast and/or axillary surgery
- Evidence of baseline sensory or motor neuropathy
- Significant history of cardiovascular disease, serious intercurrent illness or infections including known human immu immunodeficiency virus (HIV) infection
- History of prior anthracycline therapy Allergies to any study medication or Cremophor® EL
Trial locations and contacts
49 sites in 15 countries.
49 sites in 15 countries
United States10 sites
University Of New Mexico Cancer Center
Albuquerque, New Mexico, 87131
Northwest Oncology & Hematology Associates
Coral Spring, Florida, 33065
Florida Cancer Research Institute
Davie, Florida, 33328
Medical Specialists Of Palm Beaches
Lake Worth, Florida, 33467
University Medical Center, Inc
Louisville, Kentucky, 40202
Comprehensive Cancer Center
Palm Springs, California, 92262
Virginia Mason Medical Center
Seattle, Washington, 98101
Providence Cancer Center
Spokane, Washington, 99204
Moffitt Cancer Center
Tampa, Florida, 33612
Albert Einstein Cancer Center
The Bronx, New York, 10461
India8 sites
Local Institution
Bangalore, Karnataka, 560029
Local Institution
Bhopal, 462001
Local Institution
Hyderabad, 500 004
Local Institution
Mumbai, 400012
Local Institution
New Delhi, National Capital Territory of Delhi, 110 095
Local Institution
Pune, Maharashtra, 411001
Local Institution
Trivandrum, Kerala, 695011
Local Institution
Vellore, 632004
Argentina4 sites
Local Institution
Buenos Aires, Buenos Aires, 1180AAX
Local Institution
Buenos Aires, Buenos Aires, 1650
Local Institution
Capital Federal, Buenos Aires, 1417
Local Institution
Capital Federal, Buenos Aires, 1425
Germany3 sites
Local Institution
Düsseldorf, 40235
Local Institution
Erlangen, 91054
Local Institution
Jena, 07743
Peru3 sites
Local Institution
Callao, Provincia Constitucional del Callao, 2
Local Institution
Lima, Lima Province, 34
Local Institution
Lima, Lima Province, LIMA 11
Philippines3 sites
Local Institution
Cebu City, 6000
Local Institution
Davao City, 8000
Local Institution
Quezon City, 1114
Russia3 sites
Local Institution
Kazan', 420029
Local Institution
Moscow, 129128
Local Institution
Saint Petersburg, 197022
Spain3 sites
Local Institution
Barcelona, 08035
Local Institution
Jaén, 23007
Local Institution
Lleida, 25198
France2 sites
Local Institution
Bordeaux, 33000
Local Institution
Saint-Herblain, 44805
South Korea2 sites
Local Institution
Seoul, 135-710
Local Institution
Seoul, 135-720
United Kingdom2 sites
Local Institution
Coventry, Warwickshire, CV22DX
Local Institution
Nottingham, Nottinghamshire, NG5 1PB
About this study
Official title: A Randomized Phase II Biomarker Neoadjuvant Study of Sequential AC Followed by Ixabepilone Compared to Sequential AC Followed by Paclitaxel in Women With Early Stage Breast Cancer
The study will evaluate the effectiveness of ixabepilone when given after doxorubicin plus cyclophosphamide (AC) compared to standard treatment of paclitaxel given after doxorubicin plus cyclophosphamide in patients with early stage breast cancer. In addition the study will verify predefined biomarkers as well as discover new biomarkers that could identify patients who are more likely to respond to ixabepilone than standard paclitaxel based therapy.
- Conditions
- Breast Cancer
- Being tested
- Ixabepilone, Paclitaxel, Cyclophosphamide, Doxorubicin
- Keywords
- Early Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxabepiloneDrug
Also called Epothilone, IXEMPRA®, BMS-247550
Intravenous Solution, intravenous (IV), 40mg/m², Day 1 every 21 days, 12 Weeks
PaclitaxelDrug
Intravenous Solution, IV, 80mg/m², Weekly, 12 Weeks
CyclophosphamideDrug
Intravenous Solution, IV, 600mg/m², Day 1 every 21 days, 12 Weeks
DoxorubicinDrug
Intravenous Solution, IV, 60mg/m², Day 1 every 21 days, 12 Weeks
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Not described Receives: Drug: Ixabepilone; Drug: Cyclophosphamide; Drug: Doxorubicin |
| B | Active comparator | Not described Receives: Drug: Paclitaxel; Drug: Cyclophosphamide; Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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%).
Measured: 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.
Measured: 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 (20)
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.
Measured: 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)
Percentage of Participants Requiring Breast Conservation Surgery
Number of randomized participants requiring breast conservation surgery following study treatment.
Measured: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
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.
Measured: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
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.
Measured: 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.
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.
Measured: 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 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.
Measured: : 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.
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 .
Measured: 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.
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.
Measured: 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.
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.
Measured: 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
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
Measured: 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
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)
Measured: 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
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)
Measured: 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
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)
Measured: 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
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)
Measured: 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
Number of Participants by Dose for AC
Measured: 12 weeks (4 3-week cycles)
Number of Participants by Dose for Ixabepilone/Paclitaxel
Measured: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
Reason for First Dose Reduction of AC
Measured: 12 weeks (4 3-week cycles)
Reason for First Dose Reduction of Ixabepilone/Paclitaxel
Measured: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
Number of Participants With Course Delay and Reason for Delay for AC
Measured: 12 weeks (4 3-week cycles)
Number of Participants With Dose Delay and Reason for Dose Delay for Ixabepilone/Paclitaxel
Measured: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2007 (estimated)
- Study startOct 2007
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 384 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00455533
- Sponsor's protocol ID
- CA163-100
- Other IDs
- EUDRACT 2006-003047-24
- Status last verified
- Jan 2016
- First submitted
- 2 Apr 2007
- Last updated
- 24 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 27312051
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Biomarker Neoadjuvant Study of Sequential AC Followed by Ixabepilone Compared to Sequential AC Followed by Paclitaxel in Women With Early Stage Breast Cancer
- ClinicalTrials.gov ID
- NCT00455533
- Acronym / sponsor ID
- CA163-100
- Conditions
- Breast Cancer
- Keywords
- Early Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 384 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Oct 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 3 Apr 2007 (estimated)
- Results
- Posted 4 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will evaluate the effectiveness of ixabepilone when given after doxorubicin plus cyclophosphamide (AC) compared to standard treatment of paclitaxel given after doxorubicin plus cyclophosphamide in patients with early stage breast cancer. In addition the study will verify predefined biomarkers as well as discover new biomarkers that could identify patients who are more likely to respond to ixabepilone than standard paclitaxel based therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Ixabepilone, Drug: Cyclophosphamide, Drug: Doxorubicin |
| B | Active comparator | Drug: Paclitaxel, Drug: Cyclophosphamide, Drug: Doxorubicin |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed primary invasive adenocarcinoma of the breast , T2-3, N0-3, M0, with tumor size of ≥ 2 cm
- All patients with early stage breast adenocarcinoma may enroll irrespective of receptor status
- No prior treatment for breast cancer excluding therapy for DCIS
- Karnofsky performance status of 80 - 100
- left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or multiple gated acquisition (MUGA)
Key exclusion criteria (7 listed)
- women of child-bearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy during and up to 8 weeks after the last dose of the investigational drug
- Women who are pregnant or breastfeeding
- Inflammatory or metastatic breast cancer
- Unfit for breast and/or axillary surgery
- Evidence of baseline sensory or motor neuropathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IxabepiloneAlso: Epothilone, IXEMPRA®, BMS-247550Intravenous Solution, intravenous (IV), 40mg/m², Day 1 every 21 days, 12 Weeks | Drug | A |
| PaclitaxelIntravenous Solution, IV, 80mg/m², Weekly, 12 Weeks | Drug | B |
| CyclophosphamideIntravenous Solution, IV, 600mg/m², Day 1 every 21 days, 12 Weeks | Drug | A, B |
| DoxorubicinIntravenous Solution, IV, 60mg/m², Day 1 every 21 days, 12 Weeks | Drug | A, B |
Primary outcome
Percentage of Participants Achieving Pathologic Complete Response (pCR)
Time frame: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
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.
Percentage of Participants Achieving Pathologic Complete Response (pCR) in Biomarker-Defined Populations
Time frame: pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.
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%).
Percentage of Participants Achieving Pathologic Complete Response (pCR) in 20- and 26-Gene Model Subgroups
Time frame: pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.
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.
20 secondary outcomes
Percentage of Participants Achieving Clinical Objective Response
Time frame: 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)
Percentage of Participants Requiring Breast Conservation Surgery
Time frame: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
Percentage of Participants Achieving Combined pCR and Minimal Residual Cancer Burden (RCB) 1
Time frame: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
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
Time frame: 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.
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
Time frame: 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 With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-Specified Thresholds
Time frame: : 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.
Percentage of Participants With pCR/RCB1 and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds
Time frame: 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.
Percentage of Participants With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds, Estrogen-Receptor (ER) Negative Participants
Time frame: 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.
Prevalence of Biomarker Based on Optimal Threshold (Biomarker Positive Participants)
Time frame: 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
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
Time frame: 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
Severity of Any Drug-Related AEs and Gastrointestinal AEs by System Organ Class
Time frame: 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
On-Study Hematology: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase
Time frame: 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
On-Study Liver Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase
Time frame: 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
On-Study Renal Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase
Time frame: 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
Number of Participants by Dose for AC
Time frame: 12 weeks (4 3-week cycles)
Number of Participants by Dose for Ixabepilone/Paclitaxel
Time frame: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
Reason for First Dose Reduction of AC
Time frame: 12 weeks (4 3-week cycles)
Reason for First Dose Reduction of Ixabepilone/Paclitaxel
Time frame: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
Number of Participants With Course Delay and Reason for Delay for AC
Time frame: 12 weeks (4 3-week cycles)
Number of Participants With Dose Delay and Reason for Dose Delay for Ixabepilone/Paclitaxel
Time frame: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27312051Abdel-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
49 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ixabepilone, Paclitaxel and Cyclophosphamide in people with Breast Cancer, run by Bristol-Myers Squibb at 49 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, India, Argentina, Germany, Peru and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Pathologic Complete Response (pCR) (time frame: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00455533, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2016.