MEtronomic TrEatment Option in Advanced bReast cAncer

Inclusion Criteria

• Histologically or cytologically confirmed HER2-negative locally advanced or metastatic (stage IV) breast cancer.
• Maximum of one prior line of chemotherapy for advanced or metastatic breast cancer.
• Measurable or non-measurable, but radiologically evaluable (except for skin lesions), disease according to RECIST 1.1 criteria.
• Female aged 18 years or older.
• Life expectancy > 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• ER-positive disease by local laboratory, determined on most recent available tissue (latest biopsy of metastatic lesion, otherwise prior biopsy or surgical specimen).
• If previously treated with a taxane in the neoadjuvant or adjuvant setting, the period from end of treatment to disease recurrence must have been > 12 months (> 365 days).
• Radiation therapy, if given and regardless of site, must be completed at least 2 weeks prior to randomization.
• Normal hematologic status,
• Absolute neutrophil count ≥1000/mm3 (1.0 × 109/L),
• Platelets ≥ 100 × 109/L,
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Normal renal function: serum creatinine ≤ 1.5 ULN or calculated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault formula.
• Normal liver function:
• Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (< 3 × ULN) is allowed.
• Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN.
• Women of child bearing potential must have documented negative pregnancy test within 2 weeks prior to randomization and agree to acceptable birth control (non-hormonal) during and up to 6 months after trial therapy.
• Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to starting screening procedures and randomization.
• The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.

Exclusion Criteria

• More than one prior line of chemotherapy for advanced or metastatic breast cancer
• Previous treatment for advanced or metastatic disease with taxanes, or capecitabine or vinorelbine or oral cyclophosphamide.
• More than 2 lines of previous endocrine therapy for locally advanced or metastatic breast cancer.
• Known active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of Central Nervous System (CNS) metastases or spinal cord compression are eligible if they are clinically and radiologically stable for at least 4 weeks before first dose of trial treatment and have not required high-dose steroid treatment in the last 4 weeks).
• Peripheral neuropathy grade 2 or higher (CTCAE version 4.0).
• Significant uncontrolled cardiac disease (i.e. unstable angina, myocardial infarction within prior 6 months), patients classified as having a New York Heart Association (NYHA) class III or IV congestive heart failure.
• Pregnant or lactating.
• Prior history of non-breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder).
• Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol.
• Contraindications or known hypersensitivity to the trial medication or excipients.
• The use of any anti-cancer investigational agents within 30 days prior to expected start of trial treatment.