Clinical trial NCT00455533: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Early Breast Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-04-03
Enrollment: 384
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion criteria

* 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

Exclusion Criteria

* 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

Primary outcomes:
measure: Percentage of Participants Achieving Pathologic Complete Response (pCR)
timeFrame: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
measure: Percentage of Participants Achieving Pathologic Complete Response (pCR) in Biomarker-Defined Populations
timeFrame: pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.
measure: Percentage of Participants Achieving Pathologic Complete Response (pCR) in 20- and 26-Gene Model Subgroups
timeFrame: 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: Percentage of Participants Achieving Clinical Objective Response
timeFrame: 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)
measure: Percentage of Participants Requiring Breast Conservation Surgery
timeFrame: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
measure: Percentage of Participants Achieving Combined pCR and Minimal Residual Cancer Burden (RCB) 1
timeFrame: at surgery (performed 4-6 weeks after the last dose of 12 weeks of therapy)
measure: 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
timeFrame: 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.
measure: 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
timeFrame: pCR evaluated at time of surgery (4-6 weeks after the last dose of therapy); mandatory tumor tissue biopsy obtained prior to treatment.
measure: Percentage of Participants With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-Specified Thresholds
timeFrame: : 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.
measure: Percentage of Participants With pCR/RCB1 and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds
timeFrame: 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.
measure: Percentage of Participants With pCR and MDR1 Immunohistochemistry (IHC) Positivity Using Two Pre-specified Thresholds, Estrogen-Receptor (ER) Negative Participants
timeFrame: 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.
measure: Prevalence of Biomarker Based on Optimal Threshold (Biomarker Positive Participants)
timeFrame: 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
measure: 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
timeFrame: 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
measure: Severity of Any Drug-Related AEs and Gastrointestinal AEs by System Organ Class
timeFrame: 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
measure: On-Study Hematology: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase
timeFrame: 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
measure: On-Study Liver Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase
timeFrame: 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
measure: On-Study Renal Function: Worst Common Terminology Criteria of Adverse Events (CTCAE Version 3) Grade Per Participant in Ixabepilone/Paclitaxel Phase
timeFrame: 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
measure: Number of Participants by Dose for AC
timeFrame: 12 weeks (4 3-week cycles)
measure: Number of Participants by Dose for Ixabepilone/Paclitaxel
timeFrame: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
measure: Reason for First Dose Reduction of AC
timeFrame: 12 weeks (4 3-week cycles)
measure: Reason for First Dose Reduction of Ixabepilone/Paclitaxel
timeFrame: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
measure: Number of Participants With Course Delay and Reason for Delay for AC
timeFrame: 12 weeks (4 3-week cycles)
measure: Number of Participants With Dose Delay and Reason for Dose Delay for Ixabepilone/Paclitaxel
timeFrame: 12 weeks (4 3-week cycles for ixabepilone and 12 weekly doses for paclitaxel)
Other outcomes:
Locations:
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center
state: California
city: Coral Spring
country: United States
facility: Northwest Oncology & Hematology Associates
state: Florida
city: Davie
country: United States
facility: Florida Cancer Research Institute
state: Florida
city: Lake Worth
country: United States
facility: Medical Specialists Of Palm Beaches
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Louisville
country: United States
facility: University Medical Center, Inc
state: Kentucky
city: Albuquerque
country: United States
facility: University Of New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Cancer Center
state: New York
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Spokane
country: United States
facility: Providence Cancer Center
state: Washington
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Salzburg
country: Austria
facility: Local Institution
city: Vienna
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Bordeaux
country: France
facility: Local Institution
city: Saint Herblain
country: France
facility: Local Institution
city: Duesseldorf
country: Germany
facility: Local Institution
city: Erlangen
country: Germany
facility: Local Institution
city: Jena
country: Germany
facility: Local Institution
city: New Delhi
country: India
facility: Local Institution
state: Delhi
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Trivandrum
country: India
facility: Local Institution
state: Kerala
city: Pune
country: India
facility: Local Institution
state: Maharashtra
city: Bhopal
country: India
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Vellore
country: India
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Callao
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Cebu City
country: Philippines
facility: Local Institution
city: Davao City
country: Philippines
facility: Local Institution
city: Quezon City
country: Philippines
facility: Local Institution
city: Kazan
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Jaen
country: Spain
facility: Local Institution
city: Lleida
country: Spain
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Nottingham
country: United Kingdom
facility: Local Institution
state: Nottinghamshire
city: Coventry
country: United Kingdom
facility: Local Institution
state: Warwickshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.