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