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

• Conditions: Bonadonna has demonstrated that the addition of adjuvant chemotherapy (CMF) in patients presenting a breast cancer with node involvement improved disease-free survival (DFS) as well as overall survival (OS). Recently, the mature results of taxane-based clinical trials have demonstrated the benefits of adding taxanes in the adjuvant setting, in terms of DFS and OS for patients with a breast cancer with node involvement or node negative (HER2 positive or negative patients).; MedDRA version: 9.1Level: LLTClassification code 10006192Term: Breast cancer NOS

• Registration Number: EUCTR2006-006494-24-BE
• Lead Sponsor: Fédération Nationale des Centres de Lutte Contre le Cancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-08-10
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 2500

Inclusion Criteria

1) Women aged from 18 to 70 years
2) Histologically proven invasive unilateral breast cancer (regardless of the type)
3) Initial clinical condition compatible with complete initial resection
4) No residual macro or microscopic tumor after surgical excision
5) Beginning of chemotherapeutic treatment no later than day 49 after the initial surgery
6) 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
7) Patient presenting one of the following criteria :
o for N+ patients: triple negative tumor [HER2 negative and ER negative and PR negative] or [HER2 negative and PR negative status],
o 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.
8) No clinically or radiologically detectable metastases (M0)
9) No peripheral neuropathy > 1
10) WHO Performance status (ECOG) of 0 or 1
11) 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)
12) Adequate hematological function (neutrophil count = 2x109/l
platelet count =100x 109/l, Hemoglobin > 9g/dl)
13) Adequate hepatic function: ASAT and ALAT = 1.5 ULN, alkaline phosphatase = 2.5 ULN, total bilirubin = 1.0 ULN
14) Adequate renal function: serum creatinine = 1.5 ULN
15) Patients accepting contraception intake during the overall length of treatment
if of childbearing potential
16) Adequate cardiac function, LEVF value = 50% by Muga scan or echocardiography,
17) Signed written informed consent.

Women of childbearing potential (WOCBP) must be using an adequate method
of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of chemotherapy in such a manner that the risk of pregnancy is minimized. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophrectomy) or is not postmenopausal [defined as amenorrhea = 12 consecutive months; or women on hormone replacement therapy (HRT)
with documented serum follicle stimulating hormone (FSH) level > 30 IU/l]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

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

1) Bilateral breast cancer or patient with controlateral DCIS
2) Any metastatic impairment, including homolateral sub-clavicular node involvement
regardless of its type
3) Any tumor ? T4a (UICC1987) (cutaneous invasion, deep adherence, inflammatory breast cancer)
4) HER2 overexpression defined as [IHC 3+] or [IHC 2+ and FISH or CISH positive]
5) Any clinically or radiologically suspect and non-explored damage to the controlateral breast
6) Any chemotherapy, hormonal therapy or radiotherapy before surgery
7) 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
8) Previous cancer (excepted cutaneous baso-cellular epithelioma or uterin peripheral ephitelioma) in the preceding 5 years, including invasive controlateral breast cancer
9) Patients already included in another therapeutic trial involving an experimental drug
10) Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study
11) LEVF < 50% (MUGA scan or echocardiography)
12) Clinically significant cardiovascular disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension (>150/90), myocardial infarction or cerebral vascular accidents) within 6 months prior to randomization
13) Known prior severe hypersensitivity reactions to agents containing Cremophor EL
14) 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
15) Women who are pregnant or breastfeeding. Adequate birth control measures should be taken during study treatment phase
16) Women with a positive pregnancy test en enrollment or prior to study drug administration,
17) 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
18) 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 <br>3 FEC100 followed by 3 cycles of Ixabepilone versus standard epirubicin + docetaxel based protocol on the disease-free survival at 5 years.;Secondary Objective: – Efficacy: <br>– Toxicity<br>- Biology<br>- Others : cost-effectiveness evaluations and assessment of the quality of life in both groups of patients<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>