A Double-Blind, Randomized Phase 2b Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo When Administered in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Breast Cancer

Inclusion Criteria

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