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

Information source: SCRI Development Innovations, LLC
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Breast Cancer

Intervention: Ixabepilone (Drug); Cyclophosphamide (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: SCRI Development Innovations, LLC

Official(s) and/or principal investigator(s):
Denise A Yardley, M.D., Study Chair, Affiliation: SCRI Development Innovations, LLC

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.

Clinical Details

Official title: Phase II Study of Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER2-Negative Breast Cancer

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Pathologic Complete Response Rate (pCR)

Secondary outcome:

Absence of Grade-4 Non-hematologic Toxicity Excluding, Alopecia, Nausea, Vomiting and Bone Pain

Overall Survival

Disease Free Survival

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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.

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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

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Locations and Contacts

Aventura Medical Center, Aventura, Florida 33180, United States

Florida Cancer Specialists, Fort Myers, Florida 33901, United States

Watson Clinic Center for Cancer Care and Research, Lakeland, Florida 33805, United States

Medical Oncology Associates of Augusta, Augusta, Georgia 30901, United States

Northeast Georgia Medical Center, Gainesville, Georgia 30501, United States

Providence Medical Group, Terre Haute, Indiana 47802, United States

Mercy Hospital, Portland, Maine 04101, United States

Center for Cancer and Blood Disorders, Bethesda, Maryland 20817, United States

National Capital Clinical Research Consortium, Bethesda, Maryland 20817, United States

St. Louis Cancer Care, Chesterfield, Missouri 63017, United States

Methodist Cancer Center, Omaha, Nebraska 68114, United States

Hematology Oncology Associates of Northern NJ, Morristown, New Jersey 07960, United States

Oncology Hematology Care, Cincinnati, Ohio 45242, United States

Cancer Centers of Southwest Oklahoma, Lawton, Oklahoma 73505, United States

South Carolina Oncology Associates, PA, Columbia, South Carolina 29210, United States

Chattanooga Oncology Hematology Associates, Chattanooga, Tennessee 37404, United States

Family Cancer Center, Collierville, Tennessee 38017, United States

Tennessee Oncology, Nashville, Tennessee 37203, United States

South Texas Oncology and Hematology, San Antonio, Texas 78258, United States

Virginia Cancer Institute, Richmond, Virginia 23235, United States

Additional Information

Starting date: April 2009
Last updated: December 5, 2014

Page last updated: August 23, 2015

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