Randomized, open label, multicentric phase III trial evaluating the benefit of a sequential regimen associating FEC100 and Ixabepilone in adjuvant treatment of non metastatic, poor prognosis breast cancer defined as triple-negative tumor (HER2 negative - ER negative - PR negative) or HER2 negative and PR negative tumor; in node positive or node negative patients. - TavIx

Phase 1

Conditions: MedDRA version: 9.1 Level: LLT Classification code 10006192 Term: Breast cancer NOS
non-metastatic operable breast cancer

Registration Number: EUCTR2006-006494-24-FR

Lead Sponsor: Fédérationa Nationale des Centres de Lutte Contre le Cancer

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 2500

Inclusion Criteria

- Women aged from 18 to 70 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,
- Beginning of chemotherapeutic treatment no later than day 42 after the initial surgery,
- Node positive disease (positive sentinel node or positive axillary clearance) (N+)
or node negative disease (N-) with the following criteria : SBR II / III and pT>20mm,
- Patient presenting one of the following criteria :
- for N+ patients: triple negative tumor [HER2 negative and ER negative and PR negative] or [HER2 negative and PR negative status],
- for N- patients: triple negative tumor only [HER2 negative and ER negative and PR negative]
HER 2 negativity is defined as IHC 0, or IHC 1+, or [IHC 2+ and FISH or CISH negative].
Hormonal receptor (progesterone and estrogen receptors) negativity is defined as a rate <10% in immunohistochemistry.
All tumors will be centrally analysed before randomization by a regional web of reference pathologists to assess final diagnosis of HER2 expression and hormonal receptor status.
- No clinically or radiologically detectable metastases (M0),
- No peripheral neuropathy > 1,
- WHO Performance status (ECOG) of 0 or 1,
- Adequate recovery from recent surgery (at least one week must have elapsed from the time of a minor surgery (excluding breast biopsy); at least three weeks for major surgery),
- Adequate hematological function (neutrophil count = 2x109/l,
platelet count = 100x 109/l, Hemoglobin > 9g/dl),
- Adequate hepatic function: ASAT and ALAT = 1.5 ULN, alkaline phosphatase = 2.5 ULN, total bilirubin = 1.5 ULN,
- Adequate renal function: serum creatinine = 1.5 ULN,
- Patients accepting contraception intake during the overall length of treatment if of childbearing potential,
- Adequate cardiac function, LEVF value > 50% by Muga scan or echocardiography,
- Signed written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Bilateral breast cancer or patient with controlateral DCIS,
- Any metastatic impairment, including homolateral sub-clavicular node involvement, regardless of its type,
- Any tumor = T4a (UICC1987) (cutaneous invasion, deep adherence, inflammatory breast cancer),
- HER2 overexpression defined as [IHC 3+] or [IHC 2+ and FISH or CISH positive],
- Any clinically or radiologically suspect and non-explored damage to the controlateral breast,
- Any chemotherapy, hormonal therapy or radiotherapy before surgery,
- Concomittant treatment with the following strong inhibitors of CYP3A4 from 72 hours prior to the initiation of study therapy until end of treatment with ixabepilone or docetaxel: amiodarone, clarithromycin, amprenavir, delavirdine, voriconazole erythromycin, fluconazole, itraconazole, ketoconazole, indinavir, nelfinavir, ritonavir, and saquinavir.
- Previous cancer (excepted cutaneous baso-cellular epithelioma or uterin pheripheral ephitelioma) in the preceding 5 years, including invasive controlateral breast cancer,
- Patients already included in another therapeutic trial involving an experimental drug,
- Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study,
- LEVF < 50% (MUGA scan or echocardiography),
- Clinically significant cardiovascular disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension (>150/90), myocardial infaction or cerebral vascular accidents) within 6 months prior to randomization,
- Known prior severe hypersensitivity reactions to agents containing Cremophor EL,
- Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 8 weeks after treatment completion,
- Women who are pregnant or breastfeeding. Adequate birth control measures should be taken during study treatment phase,
- Women with a positive pregnancy test en enrollment or prior to study drug administration,
- Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial,
- Individual deprived of liberty or placed under the authority of a tutor.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of this trial is to evaluate the benefit from the sequential administration of 3 FEC100 followed by 3 cycles of Ixabepilone versus standard epirubicin + docetaxel based protocol on the disease-free survival at 5 years.;<br> Secondary Objective: – Efficacy:<br> – Toxicity<br> - Biology<br><br> ;<br> Primary end point(s): Disease free survival rate (DFS) at 5 years.<br><br> The relapse will be defined as :<br> - a local or regional relapse<br> - a metastatic relapse,<br> - a contraloteral breast cancer,<br> - or a death of any cause.<br><br> The DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first.<br>

Secondary Outcome Measures

Name	Time	Method

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