Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER-2 Negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00866905
Recruitment Status : Completed
First Posted : March 23, 2009
Results First Posted : November 27, 2014
Last Update Posted : December 31, 2014
Bristol-Myers Squibb
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:

We propose to evaluate ixabepilone in combination with cyclophosphamide for the neoadjuvant treatment of locally advanced breast cancer. In this regimen, ixabepilone is substituted for docetaxel, since preclinical and clinical

studies suggest that ixabepilone is more active than either docetaxel or paclitaxel. The combination of ixabepilone and cyclophosphamide could further improve the efficacy of non-anthracycline neoadjuvant therapy.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Ixabepilone Drug: Cyclophosphamide Phase 2

Detailed Description:
In this study, patients with early stage, HER2-negative breast cancer will receive neoadjuvant treatment with ixabepilone and cyclophosphamide given every three weeks for a total of six cycles. Following surgery patients with hormone receptor-positive tumors will receive anti-estrogen treatment. Patients may receive local regional radiation therapy after surgery per institutional guidelines at the investigator's discretion. Baseline tumor tissue and tumor tissue removed at the time of surgery will be tested by Oncotype Detailed Description (DX) assay to determine whether it is predictive of response to this neoadjuvant treatment regimen. This study will be one of the first investigations of the combination of ixabepilone and cyclophosphamide as neoadjuvant treatment for HER2-negative breast cancer. It will examine this treatment regimen for potential advantages gained from substitution of ixabepilone for a taxane and use of non-anthracycline agents.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 168 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER2-Negative Breast Cancer
Study Start Date : April 2009
Actual Primary Completion Date : July 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Ixabepilone/Cyclophosphamide
Systemic Therapy followed by surgery and possible radiation therapy
Drug: Ixabepilone
40 mg/m2 IV infusion over 3 hours on day 1 of a 21 day cycle for 6 cycles
Other Names:
  • Systemic therapy
  • Ixempra
Drug: Cyclophosphamide
600 mg/m2 IV infusion per institutional guidelines on day 1 of a 21 day cycle for 6 cycles
Other Names:
  • Systemic therapy
  • Cytoxan

Primary Outcome Measures :
  1. Pathologic Complete Response Rate (pCR) [ Time Frame: 6 months ]
    Pathologic complete response (pCR) rate will be evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 following neoadjuvant treatment with six (21-day) cycles of ixabepilone and cyclophosphamide

Secondary Outcome Measures :
  1. Absence of Grade-4 Non-hematologic Toxicity Excluding, Alopecia, Nausea, Vomiting and Bone Pain [ Time Frame: 3 months ]
    Non hematologic treatment-related grade 4 toxicities measured according to RECIST v1.1

  2. Overall Survival [ Time Frame: 36 months ]
    Overall survival (OS) determined as the time between day 1 cycle 1 to the date of death from any cause.

  3. Disease Free Survival [ Time Frame: 36 Months ]
    Defined as the time between Day 1 Cycle 1, and date of first documented recurrence, initiation of additional chemotherapy, or death.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female patients, age ≥18 years.
  2. Histologically confirmed invasive adenocarcinoma of the breast.
  3. Primary palpable disease confined to a breast and axilla on

    physical examination. For patients without clinically suspicious

    axillary adenopathy, the primary tumor must be larger than 2 cm

    in diameter by physical exam or imaging studies (clinical T2-T3,

    N0-N1, M0). For patients with clinically suspicious axillary

    adenopathy, the primary breast tumor can be any size (clinical

    T1-3, N1-2, M0). (T1N0M0 lesions are excluded.)

  4. Patients without clearly defined palpable breast mass or axillary

    lymph nodes but radiographically measurable tumor masses are

    acceptable. Accepted procedures for measuring breast disease

    are mammography, MRI, and breast ultrasound. This will need to

    be re-evaluated after 3 cycles and prior to surgery.

  5. Eastern Cooperative Oncology Group performance status (ECOG

    PS) 0-2.

  6. No metastatic disease, as documented by complete staging workup

    • 6 weeks prior to initiation of study treatment.
  7. No previous treatment for breast cancer.
  8. HER2-negative tumor status. HER2-negative is defined as:

    • Immunohistochemical (IHC) 0, IHC 1+ OR
    • IHC 2+ or IHC 3+ must be confirmed as FISH (fluorescence in situ

    hybridization) negative (defined by ratio <2.2).

  9. Adequate hematologic function with:

    • Absolute neutrophil count (ANC) >1500/μL.
    • Platelets ≥100,000/μL.
    • Hemoglobin ≥10 g/dL.
  10. Adequate hepatic function with:

    • Serum bilirubin ≤ the institutional upper limit of normal (ULN).
    • Aspartate aminotransferase (AST) ≤2.5 x institutional ULN.
    • Alanine aminotransferase (ALT) ≤2.5 x institutional ULN.
  11. Adequate renal function with serum creatinine ≤1.5 x ULN.
  12. Estrogen and progesterone receptor status in the primary tumor

    known or pending at the time of study registration.

  13. Knowledge of the investigational nature of the study and ability to

    provide consent for study participation.

  14. For patients who had, or will have sentinel lymph node and/or

    axillary dissection prior to initiation of study treatment, completion

    at least 4 weeks prior to starting study treatment and well-healed


  15. Bilateral, synchronous breast cancer is allowed if one primary

    tumor meets the inclusion criteria.

  16. Sufficient archived breast tumor specimen available at baseline

for the Oncotype DX assay.

Exclusion Criteria:

  1. Inflammatory breast cancer.
  2. Peripheral neuropathy (motor or sensory) ≥ grade 1 by the

    Common Terminology Criteria for Adverse Events version 3.0

    (CTCAE v 3.0).

  3. Prior radiation that included ≥30% of major bone marrow containing

    areas (pelvis, lumbar, spine).

  4. Chronic use of cytochrome P450 (CYP) 3A4 inhibitors and use of

    the following strong CYP3A4 inhibitors: ketoconazole,

    itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir,

    telithromycin, ritonavir, amprenavir, indinavir, nelfinavir,

    delavirdine, and voriconazole. Use of these agents should be

    discontinued at least 72 hours prior to initiation of study treatment.

  5. Chemotherapy within 5 years of starting study treatment except

    for low doses of agents used for anti-inflammatory indications

    such as rheumatoid arthritis, psoriasis, and connective tissue

    disorders. Although such doses and schedules cannot result in

    myelosuppression, patients must discontinue this therapy while

    they are receiving study treatment.

  6. Known or suspected hypersensitivity to Cremophor®EL

    (polyoxyethylated castor oil) or a drug formulated in

    Cremophor®EL such as paclitaxel, or any other agent given in the

    course of this study.

  7. Pregnancy or breast-feeding. A negative serum pregnancy test

    within 7 days prior to first study treatment (Day 1, Cycle 1) for all

    women of childbearing potential is required. Patients of

    childbearing potential must agree to use a birth control method

    that is approved by their study physician while receiving study

    treatment and for 3 weeks after their last dose of study treatment.

    Patients must agree to not breast-feed while receiving study


  8. Concurrent treatment with an ovarian hormonal replacement

    therapy or with hormonal agents such as raloxifene, tamoxifen or

    other selective estrogen receptor modulator (SERM). Patients

    must have discontinued use of such agents prior to beginning

    study treatment.

  9. History of malignancy treated with curative intent within the

    previous 5 years with the exception of skin cancer, cervical

    carcinoma in situ, or follicular thyroid cancer. Patients with

    previous invasive cancers (including breast cancer) are eligible if

    the treatment was completed more than 5 years prior to initiating

    current study treatment, and there is no evidence of recurrent


  10. Uncontrolled intercurrent illness including (but not limited to)

    ongoing or active infection.

  11. Chronic treatment with corticosteroid unless treatment was begun

    >6 months prior to study treatment and is at a low dose (≤20 mg

    methylprednisolone or equivalent).

  12. Use of any investigational agent within 30 days of administration

    of the first dose of study drug.

  13. Requirement for radiation therapy concurrent with neoadjuvant

    study chemotherapy.

  14. Concurrent treatment with any anti-cancer therapy other than

    those agents used in this study.

  15. Inability or unwillingness to comply with study procedures

    including follow-up visits.

  16. Mental condition or psychiatric disorder that would prevent patient

    comprehension of the nature, scope, and possible consequences

    of the study or that would limit compliance with study


  17. Any other disease(s), metabolic dysfunction, or findings from a

physical examination or clinical laboratory test result that would

cause reasonable suspicion of a disease or condition that

contraindicates the use of study drugs, that may affect the

interpretation of the results, or that renders the patient at high risk

from treatment complications

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 identifier (NCT number): NCT00866905

United States, Florida
Aventura Medical Center
Aventura, Florida, United States, 33180
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Watson Clinic Center for Cancer Care and Research
Lakeland, Florida, United States, 33805
United States, Georgia
Medical Oncology Associates of Augusta
Augusta, Georgia, United States, 30901
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Maine
Mercy Hospital
Portland, Maine, United States, 04101
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Hematology Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
Cancer Centers of Southwest Oklahoma
Lawton, Oklahoma, United States, 73505
United States, South Carolina
South Carolina Oncology Associates, PA
Columbia, South Carolina, United States, 29210
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Family Cancer Center
Collierville, Tennessee, United States, 38017
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
South Texas Oncology and Hematology
San Antonio, Texas, United States, 78258
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23235
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bristol-Myers Squibb
Study Chair: Denise A Yardley, M.D. SCRI Development Innovations, LLC

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00866905     History of Changes
Other Study ID Numbers: SCRI BRE 133
First Posted: March 23, 2009    Key Record Dates
Results First Posted: November 27, 2014
Last Update Posted: December 31, 2014
Last Verified: December 2014

Keywords provided by SCRI Development Innovations, LLC:
Breast Cancer
Neoadjuvant Therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators