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

The study is being conducted to compare progression-free survival in patients treated with sorafenib and gemcitabine/capecitabine versus patients treated with placebo and gemcitabine/capecitabine for locally advanced or metastatic breast cancer that has progressed during or following treatment with a bevacizumab-containing regimen.


Eligibility Criteria:
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.