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 PainOverall 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.
-
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
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