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

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ClinicalTrials.gov Identifier: NCT00877500
Recruitment Status : Active, not recruiting
First Posted : April 7, 2009
Last Update Posted : May 20, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Bilateral Breast Carcinoma HER2/Neu Negative Invasive Breast Carcinoma Other: Best Practice Drug: Ixabepilone Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To investigate the genomic (transcriptional profiles) and proteomic (pathway activation) features that distinguish tumors that do not achieve a pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) and correlate these features with outcome in the presence and absence of adjuvant ixabepilone.

II. To evaluate the presence of circulating tumor cells (CTCs) at baseline (before chemotherapy starts; if radiation is used, after radiation ends), during and after ixabepilone therapy or during observation.

SECONDARY OBJECTIVES:

I. To collect serial blood samples for future pharmacogenomic studies. II. To determine if the addition of adjuvant ixabepilone will improve recurrence-free survival in patients that have significant residual HER 2/neu-negative breast cancer after NST.

III. To assess the toxicity of adjuvant ixabepilone in this group of patients.

OUTLINE: Participants are randomized to 1 of 2 groups.

GROUP I (IXABEPILONE): Participants receive ixabepilone intravenously (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.

GROUP II (STANDARD OF CARE): Participants receive standard of care for 18 weeks.

After completion of study treatment, participants are followed up every 3 months for 2 years and every 6 months for 3 years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Randomized Study of Ixabepilone vs. Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2/Neu-Negative Breast Cancer
Actual Study Start Date : March 30, 2009
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : April 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Ixabepilone

Arm Intervention/treatment
Experimental: Group I (ixabepilone)
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
Given IV
Other Names:
  • (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

Active Comparator: Group II (standard of care)
Participants receive standard of care for 18 weeks.
Other: Best Practice
Receive standard of care
Other Names:
  • standard of care
  • standard therapy




Primary Outcome Measures :
  1. Genomic (transcriptional profiles) and proteomic (pathway activation) features that distinguish tumors [ Time Frame: Up to 5 years ]
    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.

  2. Significant circulating tumor cells (CTCs) [ Time Frame: At 18 weeks ]
    Presence of any cell per 7.5 ml of whole blood.


Secondary Outcome Measures :
  1. Incidence of adverse events in each group [ Time Frame: Up to 5 years ]
    Chi-square tests of independence and generalized logistic regression models will be used.

  2. Recurrence-free survival [ Time Frame: Up to 5 years ]
    Will be estimated non-parametrically using the Kaplan-Meier product limit method. Cox proportional hazards regression models will be used to model recurrence-free survival as a function of treatment group.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
  • All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP will be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The principal investigator (PI) will immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00877500


Locations
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United States, Illinois
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453-2699
United States, Texas
Lyndon Baines Johnson General Hospital
Houston, Texas, United States, 77026-1967
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Funda Meric-Bernstam M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00877500     History of Changes
Other Study ID Numbers: 2008-0435
NCI-2018-01849 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2008-0435 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: April 7, 2009    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Epothilones
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents