Sorafenib and Paclitaxel in Treating Patients With Metastatic Breast Cancer

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically* confirmed breast cancer

  • Stage IV (metastatic) disease

    • Radiographic evidence of metastases NOTE: *Histological confirmation of the actual metastasis is not required.

• Measurable disease by RECIST criteria defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (i.e., physical examination, CT scan, MRI, or x-ray) or ≥ 10 mm by spiral CT scan

  • No prior radiotherapy unless growth has been documented following radiotherapy

• Primary tumor or metastatic tumor HER2-negative, defined as the following:

  • Immunohistochemistry of 0 or 1+ OR the equivalent, if an automated quantitative assay is used
  • HER2 fluorescent in situ hybridization (FISH) assay negative as defined by a HER2:chromosome 17 centromeric probe ratio < 1.8 (or < 2.2 if immunohistochemistry is less than 3+ or equivalent) OR equivalent values for negative FISH assays that do not normalize to chromosome 17
• Hormone-receptor positive (estrogen receptor-[ER] or progesterone receptor [PgR]-positive) disease or hormone receptor-negative (ER- or PgR-negative) disease
• Tumor block from initial breast cancer primary or a biopsy of a metastatic site must be available for correlative studies
• Brain metastases allowed provided the patient is stable after completion of treatment (i.e., surgery and/or radiotherapy), asymptomatic, and off steroids with 2 consecutive stable brain scans at least 4 weeks after radiotherapy

Exclusion criteria:

• Bone-only or other nonmeasurable-only disease
• Newly diagnosed brain metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status 0-1
• Life expectancy > 6 months
• Menopausal status not specified
• WBC ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT transaminases ≤ 2.5 times ULN (< 5 times ULN if liver involvement)
• Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min
• INR < 1.5 OR PT/PTT normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to and during (women and men) and for at least 3 months after (men) study therapy
• Able to swallow and absorb oral medications

Exclusion criteria:

• Active or uncontrolled medical illness (e.g., active infection > CTCAE grade 2), including any of the following:

  • HIV or chronic hepatitis B or C
  • Uncontrolled diabetes
  • NYHA class II-IV uncompensated congestive heart failure
  • Unstable angina (anginal symptoms at rest)
  • New onset angina (i.e., began within the past 3 months)
  • Coronary artery disease
• Myocardial infarction within the past 6 months
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Evidence of bleeding diathesis or coagulopathy
• Pulmonary hemorrhage/bleeding event > CTCAE grade 2 within 4 weeks of first dose of study drug
• Any other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of first study drug
• Thrombotic or embolic events (i.e., cerebrovascular accident), including transient ischemic attacks within the past 6 months
• Hypertension that cannot be controlled with medication to ≤ 150/90 mm Hg
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate
• Prior invasive cancer other than breast cancer except nonmelanoma skin cancer
• Chronic nonhealing wound or ulcer

PRIOR CONCURRENT THERAPY:

• No more than 1 prior chemotherapy regimen for metastatic breast cancer (MBC)

• At least 3 weeks since prior hormonal therapy for MBC or adjuvant or neoadjuvant chemotherapy

  • More than 1 year since adjuvant paclitaxel
• At least 4 weeks since major thoracic, abdominal, or pelvic surgery and recovered
• At least 3 weeks since prior and no concurrent investigational drugs
• Concurrent bisphosphonates allowed
• Concurrent anticoagulation agents (i.e., warfarin or heparin) allowed
• No anticipated need for or concurrent radiotherapy
• No concurrent Hypericum perforatum (St. John wort) or rifampin (rifampicin)
• No other concurrent anti-neoplastic drugs