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

• Status: Completed
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this study is to determine the efficacy and safety of sorafenib in the neoadjuvant setting in patients with primary breast cancer

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: German Breast Group
• Collaborator: Bayer
• Treatments: Niacinamide; Sorafenib

Criteria

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)