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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00866905
First received: March 19, 2009
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Breast Cancer
Drug: Ixabepilone
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER2-Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • To evaluate the pathologic complete response (pCR) rate following neoadjuvant treatment with six cycles of ixabepilone and cyclophosphamide in HER2-negative locally advanced breast cancer [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To characterize the safety and tolerability of the neoadjuvant combination of ixabepilone and cyclophosphamide [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • To determine the disease-free survival (DFS) following neoadjuvant treatment with the combination of ixabepilone and cyclophosphamide [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To determine the overall survival (OS) following neoadjuvant treatment with the combination of ixabepilone and cyclophosphamide [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To evaluate the clinical response rate (clinical complete response [cCR] + clinical partial response [cPR]) to neoadjuvant treatment with the combination of ixabepilone and cyclophosphamide [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To evaluate the Oncotype DX score in predicting the efficacy of neoadjuvant ixabepilone/cyclophosphamide [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 168
Study Start Date: April 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 wound
  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 treatment.
  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 disease.
  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 requirements.
  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 -
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866905

Locations
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
Investigators
Study Chair: Denise A Yardley, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00866905     History of Changes
Other Study ID Numbers: SCRI BRE 133
Study First Received: March 19, 2009
Last Updated: April 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by SCRI Development Innovations, LLC:
Breast Cancer
Ixabepilone
Ixempra
Cyclophosphamide
Cytoxan
Neoadjuvant Therapy

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

ClinicalTrials.gov processed this record on July 26, 2014