Phase IB/II Trial Combining Vinorelbine With Sorafenib as First-Line Treatment in Patients With Metastatic Breast Cancer

Inclusion Criteria: * Women affected by histologically proven metastatic breast cancer. * Tumor not susceptible to therapy with trastuzumab, defined as FISH negative for HER-2 amplification or immunohistochemistry 0-1+ for HER-2 expression. * Female, age ≥ 18. * Documented measurable disease by appropriate radiologic imaging according to RECIST criteria (see Appendix E). Lesions in previously irradiated areas are not considered measurable disease, unless progression has been documented post-radiation. * ECOG performance status 0-1 (see Appendix B) * Life expectancy \> 6 months. * Adequate bone marrow function, as indicated by: * Hemoglobin ≥ 90 g/L * Neutrophils ≥ 1.5 x 109/L * Platelets ≥ 100 x 109/L * Adequate renal function, as indicated by serum creatinine ≤1.5 times the upper limit of normal and/or Creatinine Clearance calculated as \>50% lower normal limit, or estimated as ≥ 50 ml/min (Appendix C). * Adequate liver function, as indicated by: * bilirubin ≤ 1.5 times upper normal limit; * AST and ALT ≤ 2 times upper normal limit. * Left ventricular ejection fraction (LVEF) ≥50% as measured by either multigated acquisition (MUGA) scan or echocardiogram (ECHO). * No therapy for breast cancer in the 4 weeks preceding the therapy start. * Women of childbearing potential must be using adequate contraception and have a negative pregnancy test at the time of enrollment. * Patient able to understand and give written informed consent. Exclusion Criteria: * Patients with locally advanced breast cancer or stage IIIb only. * Presence of only non-measurable disease. * Previous (neo)adjuvant chemotherapy with vinorelbine. * Any previous anti-angiogenic therapy. * Any previous chemotherapy for metastatic breast cancer. Previous hormonal treatments or radiotherapy for metastatic disease are allowed. * Radiotherapy, chemotherapy or hormonal therapy for breast cancer in the last 4 weeks prior to starting the study treatment. * Major surgery within 4 weeks of first study treatment, or minor surgery (including placement of an access device) within 7 days of therapy start. * Presence of life-threatening disease or central nervous system localizations. * Evidence of HER-2 positive breast cancer, defined as FISH-positive for amplification or score 3+ by immunohistochemistry. * Any other possibly active primary tumor, except basal cell carcinoma of the skin, or carcinoma in situ of the cervix. * Clinically significant hepatic disease with respect to hepatitis B, hepatitis C, cirrhosis or other liver diseases. * Uncontrolled bacterial, viral or fungal infection. * Previous history of ischemic disease. * Patients with previous history of thrombo-embolic events, or with documented risk factors for thrombotic disease other than cancer. * History of gross hemorrhage within the past 6 months (e.g., hemoptysis or hematuria requiring medical intervention). * Uncontrolled hypertension. * Other serious medical conditions, such as uncontrolled cardiac disease, severe pulmonary disease, uncontrolled diabetes. * Patient exhibiting confusion or disorientation. * Any condition (medical, social, psychological, geographical) that would prevent adequate follow-up. * Patient is pregnant, or is breast-feeding, or is unwilling to use adequate contraception. * Failure to give informed consent.