Ixabepilone in Treating Participants With Significant Residual Disease of HER2/Neu Negative Invasive Breast Cancer After Systemic Therapy

NCT00877500 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2008-0435NCI-2018-01849
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well ixabepilone compared with standard of care works in treating patients with HER2/Neu negative breast cancer that remains after undergoing systemic therapy. Ixabepilone works by blocking cell division which may cause cancer cell death.

Conditions

Bilateral Breast Carcinoma; HER2/Neu Negative; Invasive Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Genomic (transcriptional profiles) and proteomic (pathway activation) features that distinguish tumors

  RPPA will be used to objectively quantify (phospho)protein expression. Functional activation of the pathway will be defined as an increase in phosphorylation of at least one half of the components of each pathway above the median RPPA quantified activation across the entire tumor set. Data will be analyzed for the presence of clusters based on differential protein expression by using available methods with the R statistical software package. A variety of unsupervised clustering methods (including hierarchical clustering, K-means, independent component analysis, mutual information, and gene shaving) will be used to classify the samples into statistically similar groups.

  Up to 5 years

• Significant circulating tumor cells (CTCs)

  Presence of any cell per 7.5 ml of whole blood.

  At 18 weeks

Secondary Outcomes (2)

• Incidence of adverse events in each group

  Up to 5 years

• Recurrence-free survival

  Up to 5 years

Study Arms (2)

Group I (ixabepilone)

EXPERIMENTAL

Participants receive ixabepilone IV over 3 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Ixabepilone

Group II (standard of care)

ACTIVE COMPARATOR

Participants receive standard of care for 18 weeks.

Other: Best Practice

Interventions

Best Practice OTHER

Receive standard of care

Also known as: standard of care, standard therapy

Group II (standard of care)

Ixabepilone DRUG

Given IV

Also known as: (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione, Azaepothilone B, BMS 247550, BMS-247550, BMS247550, Epothilone, Epothilone-B BMS 247550, Ixempra

Group I (ixabepilone)

Eligibility Criteria

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

You may qualify if:

• Patients with histologic confirmation of invasive HER2/neu-negative breast cancer (immunohistochemistry \[IHC\] 0-1+ or fluorescence in situ hybridization \[FISH\]-negative) that have received complete anthracycline and taxane neoadjuvant systemic therapy and that at the time of surgery are expected to have significant residual disease. Therapy should include at least 4 cycles of an anthracycline-based regimen (adriamycin-cytoxan \[AC\], 5-fluorouracil/adriamycin/intravenous \[IV\] cyclophosphamide \[FAC\], fluorouracil-epirubicin-IV cytoxan \[FEC\]) and 12 weeks of a taxane-based regimen (weekly paclitaxel, every 3-week docetaxel).
• Patients who did not complete therapy due to disease progression are eligible.
• Patients with bilateral breast cancers are eligible.
• Patients should have a Karnofsky performance scale of \>= 70%.
• Peripheral granulocyte count of \>= 1500/mm\^3.
• Platelet count \>= 100000 mm\^3.
• Bilirubin within normal laboratory values.
• Alkaline phosphatase may be up to 1.5 x upper limit of normal (ULN) of the institution.
• Transaminases (alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\]) may be up to 1.5 x upper limit of normal (ULN) of the institution.
• Creatinine levels within normal range.
• Negative serum pregnancy test for a woman of childbearing potential.
• Women of childbearing potential (WOCP) must use a reliable and appropriate contraceptive method during the study and 6 months after chemotherapy is completed. Women of childbearing potential (WOCBP) are women who are not menopausal for 12 months or had no previous surgical sterilization.
• Patients must agree to have study tissue collections and blood sample collections.
• Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.
• Patients should have their surgical tissues evaluated for residual cancer burden (RCB) and be used for correlative studies.

You may not qualify if:

• Patients whose tumors express HER2 protein or have HER2/neu gene amplification.
• Patients with a history of other invasive malignancies diagnosed and treated within the previous 5 years, except non-melanoma skin cancer and non-invasive cervical cancer.
• Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper gastrointestinal \[GI\] tract ulceration).
• Patients with a pre-existing peripheral neuropathy \> grade 1.
• Evidence of distant metastases.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453-2699, United States

Location

Lyndon Baines Johnson General Hospital

Houston, Texas, 77026-1967, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Gonzalez-Angulo AM, Lei X, Alvarez RH, Green MC, Murray JL, Valero V, Koenig KB, Ibrahim NK, Litton JK, Nair L, Krishnamurthy S, Hortobagyi GN, Meric-Bernstam F. Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer. Clin Breast Cancer. 2015 Oct;15(5):325-31. doi: 10.1016/j.clbc.2015.03.004. Epub 2015 Mar 24.

  PMID: 25913905 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

Practice Guidelines as Topic; Standard of Care; ixabepilone; Epothilones

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Funda Meric-Bernstam

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 6, 2009
• First Posted: April 7, 2009
• Study Start: March 30, 2009
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (3)