Neoadjuvant Chemotherapy Including Sorafenib in Women With Previously Untreated Primary Breast Cancer (SOFIA)

Inclusion Criteria:

• Unilateral or bilateral primary carcinoma of the breast,
• Tumor lesion in the breast with a palpable size of >= 2 cm. The lesion has to be measurable in two-dimensions preferably by sonography. In case of inflammatory disease the extent of inflammation can be used as measurable lesion;
• Patients should have stages of disease in which adjuvant chemotherapy would be considered.
• Women of childbearing potential must have a negative serum pregnancy test
• Negative HER-2/neu status
• Karnofsky Performance status index >= 80%;
• Normal cardiac function
• Laboratory requirements:

Absolute neutrophile count (ANC) >= 2,0 x 109/L and Platelets >= 100 x 109/L and Hemoglobin >= 10 g/dL (>= 6.2 mmol/L) INR ≤ 1.5 ULN and PTT ≤ 1.5 ULN within 14 days prior to enrolment ASAT or ALAT < 2.5 x ULN Alkaline phosphatase ≤ 5 UNL. Patients with ASAT and/or ALAT > 1,5 x UNL associated with alkaline phosphatase > 2,5 x UNL are not eligible for the study Total bilirubin < 1 X UNL Creatinine ≤ 175 µmol/L (2 mg/dl). The calculated creatinine clearance should be ≥ 60 mL/min.

Paraffin tumor tissue block and each one serum and one plasma sample centrally made available

• Complete staging work-up within 3 months prior to registration.
• Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or a cooperating center.

Exclusion Criteria:

• Patients with low or moderate risk, which are only doubtful candidates for adjuvant chemotherapy and do not fulfil the inclusion criteria No. 5.
• Evidence of distant metastasis;
• Prior chemotherapy for any malignancy;
• Prior radiation therapy for breast cancer;
• Preexisting rhagades at hand and feet and other skin problems (e.g. psoriasis)
• Pregnant or lactating patients.
• Pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI criteria; 7. Concurrent treatment with: Chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (< 20 mg methylprednisolone or equivalent); Sex hormones. Prior treatment must be stopped before study entry; Patients with increased risk of bleeding due to concurrent therapeutic or prophylactic anticoagulative treatment. Low dose of coumarines are permitted.

Other experimental drugs or any other anti-cancer therapy; Drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days or their expected need 8. Other serious illness or medical condition:

• Previous malignant disease without being disease-free of less than 5 years (except CIS of the Cervix and non-melanomatous skin cancer)
• Known or suspected congestive heart failure (≥NYHA II) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease
• Thrombotic or embolic events
• Hemorrhage/bleeding event ≥ Grade 3 within 4 weeks prior study entry
• Evidence or history of bleeding diathesis or coagulopathy
• History of significant neurological or psychiatric disorders
• Patients with seizure disorders requiring medication such as steroids or antiepileptics
• Currently active infection
• History of HIV infection or chronic hepatitis B or C
• Serious non healing wound, ulcer or bone fracture
• Patients with prior immunosuppressive treatment
• Severe pulmonary condition/illness
• Disease significantly affecting gastrointestinal function,
• Patients with severe liver disease
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
• Definite contraindications for the use of corticosteroids
• Inadequate general condition (not fit for anthracycline/taxane-containing chemotherapy)