Phase 2b Study of Taxol Plus Sorafenib or Placebo in Patients With Advanced Breast Cancer

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the breast

  * Locally recurrent or metastatic disease

    * Locally recurrent disease not amenable to resection with curative intent
* Measurable or evaluable disease
* No HER-2 overexpression (defined as positive for gene amplification by FISH or 3+ overexpression by IHC)

  * No unknown HER-2 status
* No active brain metastases

  * Patients with neurological symptoms and known brain metastases treated with definitive therapy must undergo contrast CT scan or brain MRI to exclude active brain metastasis

    * Previously treated brain metastases allowed provided at least 3 months since prior definitive therapy (including steroids) AND no evidence of disease
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Male or female
* Menopausal status not specified
* ECOG performance status 0-1
* Not pregnant or nursing for ≥ 2 weeks after completion of study therapy
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study therapy
* Hemoglobin ≥ 9.0 g/dL
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
* ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
* INR ≤ 1.5 and aPTT within normal limits

  * Anticoagulation therapy (e.g., warfarin or heparin) allowed

    * Stable INR required for patients on warfarin
* Creatinine ≤ 1.5 times the ULN
* Able to swallow and retain oral medication
* More than 4 weeks since prior significant traumatic injury
* No evidence or history of bleeding diathesis or coagulopathy
* No serious nonhealing wound, ulcer, or bone fracture
* No substance abuse or medical, psychological, or social condition that would interfere with study participation or evaluation of study results
* No pre-existing peripheral neuropathy ≥ grade 2
* No clinically significant cardiac disease, including any of the following:

  * New York Heart Association class II-IV congestive heart failure
  * Unstable angina (i.e., angina symptoms at rest) or new-onset angina within the past 3 months
  * Myocardial infarction within the past 6 months
* No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
* No uncontrolled hypertension (i.e., systolic blood pressure \[BP\] \> 150 mm Hg or diastolic BP \> 90 mm Hg despite optimal medical management)
* No thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident, including transient ischemic attacks within the past 6 months
* No pulmonary hemorrhage or bleeding event \> grade 2 within the past 4 weeks
* No other hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks
* No active clinically serious infection \> grade 2
* No known HIV infection or chronic hepatitis B or C
* No other prior or concurrent cancer except carcinoma in situ of the cervix, treated basal cell skin cancer, superficial bladder tumors (e.g., Ta and Tis), or any cancer curatively treated for \> 5 years
* No known or suspected allergy to sorafenib tosylate or hypersensitivity to paclitaxel or drugs using the vehicle Cremophor

PRIOR CONCURRENT THERAPY:

* More than 12 months since prior adjuvant or neoadjuvant taxane therapy
* At least 3 weeks since other prior adjuvant chemotherapy
* At least 3 weeks since prior hormonal therapy for locally recurrent or metastatic disease
* No prior chemotherapy for locally recurrent or metastatic breast cancer
* More than 4 weeks since prior major surgery or open biopsy
* At least 3 weeks since prior radiotherapy

  * Previously irradiated area must not be the only site of disease
* More than 30 days or 5 half-lives, whichever is longer, since prior investigational drug

  * No prior or concurrent bevacizumab or any other licensed or investigational drugs that target VEGF or VEGF-receptor
* More than 3 weeks since prior and no concurrent Hypericum perforatum (St. John's wort ) or rifampin (rifampicin)
* No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
* No concurrent irinotecan hydrochloride or doxorubicin hydrochloride
* No other concurrent anticancer therapy (i.e., chemotherapy, radiotherapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
* No concurrent nonconventional therapies (e.g., herbal)
* No concurrent palliative radiotherapy