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