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

NCT00455533 | Completed Phase 2 Results

• 2 other identifiers: CA163-100EUDRACT 2006-003047-24
• Study Type: interventional
• Target: 384
• Locations: 15 countries
• Sites: 49

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.

Conditions

Breast Cancer

Keywords

Early Breast Cancer

Outcome Measures

Primary Outcomes (3)

• 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 (20)

• Percentage of Participants Achieving Clinical Objective Response

  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

  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

  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

  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

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

Study Arms (2)

A

EXPERIMENTAL

Drug: Ixabepilone; Drug: Cyclophosphamide; Drug: Doxorubicin

B

ACTIVE COMPARATOR

Drug: Paclitaxel; Drug: Cyclophosphamide; Drug: Doxorubicin

Interventions

Ixabepilone DRUG

Intravenous Solution, intravenous (IV), 40mg/m², Day 1 every 21 days, 12 Weeks

Also known as: Epothilone, IXEMPRA®, BMS-247550

A

Paclitaxel DRUG

Intravenous Solution, IV, 80mg/m², Weekly, 12 Weeks

B

Cyclophosphamide DRUG

Intravenous Solution, IV, 600mg/m², Day 1 every 21 days, 12 Weeks

A; B

Doxorubicin DRUG

Intravenous Solution, IV, 60mg/m², Day 1 every 21 days, 12 Weeks

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (49)

Comprehensive Cancer Center

Palm Springs, California, 92262, United States

Location

Northwest Oncology & Hematology Associates

Coral Spring, Florida, 33065, United States

Location

Florida Cancer Research Institute

Davie, Florida, 33328, United States

Location

Medical Specialists Of Palm Beaches

Lake Worth, Florida, 33467, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University Medical Center, Inc

Louisville, Kentucky, 40202, United States

Location

University Of New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Albert Einstein Cancer Center

The Bronx, New York, 10461, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Providence Cancer Center

Spokane, Washington, 99204, United States

Location

Local Institution

Buenos Aires, Buenos Aires, 1180AAX, Argentina

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Buenos Aires, Buenos Aires, 1650, Argentina

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Capital Federal, Buenos Aires, 1417, Argentina

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Capital Federal, Buenos Aires, 1425, Argentina

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Salzburg, 5020, Austria

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Vienna, 1090, Austria

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Bordeaux, 33000, France

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Saint-Herblain, 44805, France

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Düsseldorf, 40235, Germany

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Erlangen, 91054, Germany

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Jena, 07743, Germany

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Bangalore, Karnataka, 560029, India

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Trivandrum, Kerala, 695011, India

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Pune, Maharashtra, 411001, India

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New Delhi, National Capital Territory of Delhi, 110 095, India

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Bhopal, 462001, India

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Hyderabad, 500 004, India

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Mumbai, 400012, India

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Vellore, 632004, India

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Bologna, 40138, Italy

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Lima, Lima Province, 34, Peru

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Lima, Lima Province, LIMA 11, Peru

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Callao, Provincia Constitucional del Callao, 2, Peru

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Cebu City, 6000, Philippines

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Davao City, 8000, Philippines

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Quezon City, 1114, Philippines

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Kazan', 420029, Russia

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Moscow, 129128, Russia

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Saint Petersburg, 197022, Russia

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Singapore, 308433, Singapore

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Seoul, 135-710, South Korea

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Seoul, 135-720, South Korea

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Barcelona, 08035, Spain

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Jaén, 23007, Spain

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Lleida, 25198, Spain

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Taipei, 100, Taiwan

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Taipei, 11217, Taiwan

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Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

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Coventry, Warwickshire, CV22DX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27312051 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ixabepilone; Epothilones; Paclitaxel; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2007
• First Posted: April 3, 2007
• Study Start: October 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: February 24, 2016
• Results First Posted: April 4, 2011

Record last verified: 2016-01

Locations

SG (1); DE (3); ES (3); PH (3); IT (1); IN (8); PE (3); GB (2); AR (4); RU (3); KR (2); TW (2); US (10); AU (2); FR (2)