1st or 2nd Line MBC (Metastatic Breast Cancer) With Previous Avastin (Bevacizumab) Therapy

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast.
• Measurable or evaluable locally advanced or metastatic disease.
• Age ≥18 years.
• Disease progression during or after treatment with a bevacizumab-containing regimen in the adjuvant or first-line metastatic setting.
• Patients must have discontinued chemotherapy at least 3 weeks prior to randomization.
• No more than one prior chemotherapy regimen for locally advanced or metastatic disease.
• Prior hormonal therapy allowed provided it has been discontinued prior to randomization.
• Prior radiation therapy is allowed but must be completed at least 3 weeks prior to randomization. Previously radiated area(s) must not be the only site of disease.
• ECOG Performance Status of 0 or 1.
• Adequate bone marrow, liver, and renal function
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization, and must agree to use adequate contraception prior to study entry, for the duration of study participation and 28 days after the last study drug dosing.
• Patients must be able and willing to sign a written informed consent.
• Patients must be able to swallow and retain oral medication.

Exclusion criteria

• Patients with breast cancer over-expressing human epidermal growth factor receptor 2 (HER-2) (gene amplification by FISH or 3+ over-expression by immunohistochemistry). Patients with unknown HER-2 status are not eligible.
• Patients with active brain metastases.
• Major surgery, open biopsy, or significant traumatic injury within 4 weeks of randomization.
• Prior use of gemcitabine/capecitabine or sorafenib.
• Evidence or history of bleeding diathesis or coagulopathy.
• Serious, non-healing wound, ulcer, or bone fracture.
• Substance abuse, or medical, psychological, or social condition that may interfere with the patient's participation in the study or evaluation of the study results.
• Use of cytochrome P450 enzyme-inducing anti-epileptic drugs is not allowed.
• Clinically significant cardiac disease
• Uncontrolled hypertension
• Thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event > NCI-CTCAE Grade 2 within 4 weeks of randomization.
• Any other hemorrhage/bleeding event ≥ NCI-CTCAE Grade 3 within 4 weeks of randomization.
• Active clinically serious infection > NCI-CTCAE Grade 2.
• Known HIV infection or chronic hepatitis B or C (the safety and effectiveness of sorafenib in this patient population have not been studied).
• Previous or concurrent cancer that is distinct in primary site or histology from breast cancer EXCEPT cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis] or any cancer curatively treated > 5 years prior to randomization.
• Known or suspected allergy to sorafenib or gemcitabine/capecitabine.
• Prior or concurrent use of St. John's Wort or rifampin (rifampicin) within 3 weeks of randomization.
• Concurrent anti-cancer therapy other than gemcitabine/capecitabine and sorafenib/placebo.
• Prior treatment with any agent that targets VEGF or VEGFR (licensed or investigational), except bevacizumab.
• Women who are pregnant or breast-feeding.
• Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, preceding randomization.
• Inability to comply with protocol and/or not willing or not available for follow-up assessments.
• Any condition which in the investigator's opinion makes the patient unsuitable for the study participation.