- To evaluate the benefit from sequential administration of 3 courses of combination chemotherapy (FEC100) followed by 3 courses of ixabepilone versus docetaxel on the 5-year disease-free survival of women with nonmetastatic, poor-prognosis breast cancer.
- To compare the 5-year distant metastasis-free survival.
- To compare the 5-year event-free survival.
- To compare the 5-year overall survival.
- To compare the safety profiles for the two chemotherapy regimens.
- To identify and/or validate predictive-gene expression profiles of clinical response/resistance to the two treatment regimens.
- To bank frozen and fixed tumor and frozen serum prospectively for future translational studies in both genomics and proteomics (transcriptome and proteome analyses, tissue array analyses).
- To compare the cost-effectiveness of these 2 regimens.
- To compare the quality-of-life of patients treated with these 2 regimens.
OUTLINE: This is a multicenter study. Patients are stratified according to participating center, menopausal status (pre- vs post-menopausal), and tumor hormone-receptor status (triple-negative vs progesterone-receptor negative, HER negative, and estrogen-receptor [ER] positive). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive epirubicin hydrochloride IV, fluorouracil IV, and cyclophosphamide IV every 3 weeks in courses 1-3 and docetaxel IV alone every 3 weeks in courses 4-6.
- Arm II: Patients receive treatment in courses 1-3 as in arm I and ixabepilone IV alone every 3 weeks in courses 4-6.
In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also complete a quality of life questionnaire periodically.
After completion of study treatment, patients are followed periodically for up to 10 years.
- Histologically proven invasive unilateral breast cancer (regardless of the type)
- Initial clinical condition compatible with complete initial resection
- No residual macro or microscopic tumor after surgical excision
- Node-positive disease (i.e., positive sentinel node or positive axillary clearance) (N+) or node-negative disease (-) meeting the following criteria :
- Stage II or III disease
- pT > 20 mm (T1-4)
- Patients must meet 1 of the following hormone-receptor criteria:
- Node-positive patients: triple-negative* tumor (HER2 negative, estrogen-receptor [ER] negative, and progesterone receptor [PR] negative) OR double-negative (HER2 negative, PR negative, and ER+)
- Node-negative patients: triple-negative* tumor only
- NOTE: *Hormone-receptor negativity is defined as ER < 10% and PR < 10% by IHC and HER2 negativity is defined as IHC 0-1+ OR IHC 2+ and FISH or CISH negative
- Must be able to begin chemotherapy no later than day 49 after the initial surgery
- Clinically or radiologically detectable metastases (M0)
- Bilateral breast cancer or contralateral ductal carcinoma in situ
- Any metastatic impairment, including homolateral subclavicular node involvement, regardless of its type
- Any tumor ≥ T4a (cutaneous invasion, deep adherence, inflammatory breast cancer)
- HER 2 overexpression defined as IHC 3+ OR IHC 2+ and FISH or CISH positive
- Any clinically or radiologically suspect and non-explored damage to the contralateral breast
- Pre- or postmenopausal
- ECOG performance status 0-1
- Peripheral neuropathy ≤ grade 1
- Neutrophil count ≥ 2,000/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin > 9 g/dL
- AST and ALT ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN
- Total bilirubin ≤ 1.0 times ULN
- Serum creatinine ≤ 1.5 times ULN
- LVEF ≥ 50% by MUGA scan or echocardiography
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for up to 8 weeks after completion of study treatment
- Previous cancer (except cutaneous baso-cellular epithelioma or uterine peripheral epithelioma) in the preceding 5 years, including invasive contralateral breast cancer
- Patients with any other concurrent severe and/or uncontrolled medical disease or infection that could compromise participation in the study
- Clinically significant cardiovascular disease within the past 6 months including any of the following:
- Unstable angina
- Congestive heart failure
- Uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg)
- Myocardial infarction
- Cerebral vascular accidents
- Known prior severe hypersensitivity reactions to agents containing Cremophor EL
- Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Patients deprived of liberty or placed under the authority of a tutor
PRIOR CONCURRENT THERAPY:
- At least 2 weeks since prior minor surgery (excluding breast biopsy) and adequately recovered
- At least 3 weeks since prior major surgery and adequately recovered
- No prior chemotherapy, hormonal therapy, or radiotherapy
- More than 72 hours since prior and no concurrent treatment with any of the following strong inhibitors of CYP3A4:
- No concurrent participation in another therapeutic trial involving an experimental drug
Last updated: 03/26/2012