Safety and Efficacy Comparison of Docetaxel and Ixabepilone in Non Metastatic Poor Prognosis Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: cyclophosphamide; Docetaxel; epirubicin hydrochloride; fluorouracil; ixabepilone
Intervention description: 500 mg/m² every 3 weeks; 100 mg/m² every 3 weeks; 100 mg/m² every 3 weeks; 500 mg/m² every 3 weeks; 40 mg/m² every 3 weeks
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Fluorouracil; Epirubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 762.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Giving more than one
      drug (combination chemotherapy) and giving them after surgery may kill any tumor cells
      remaining after surgery. It is not yet known whether docetaxel is more effective than
      ixabepilone when given after surgery and combination chemotherapy in treating breast cancer.

      PURPOSE: This randomized phase III trial is studying giving combination chemotherapy followed
      by docetaxel or ixabepilone to compare how well they work in treating patients who have
      undergone surgery for nonmetastatic breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

        Inclusion criteria:

          -  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

        Exclusion criteria:

          -  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

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  Female

          -  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

        Exclusion criteria:

          -  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:

               -  Amiodarone

               -  Clarithromycin

               -  Amprenavir

               -  Delavirdine

               -  Voriconazole

               -  Erythromycin

               -  Fluconazole

               -  Itraconazole

               -  Ketoconazole

               -  Indinavir

               -  Nelfinavir

               -  Ritonavir

               -  Saquinavir

          -  No concurrent participation in another therapeutic trial involving an experimental
             drug