1st or 2nd line mbc (metastatic breast cancer) with previous avastin (bevacizumab) therapy

Conditions: Breast Cancer

Summary: 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.

Keywords: breast cancer