Women with previously untreated primary breast cancer. MedDRA version: 9.1 Level: LLT Classification code 10057654 Term: Breast cancer female
Conditions
Interventions
Trade Name: Nexavar
Product Code: BAY 43-9006
Pharmaceutical Form: Tablet
Sponsors
GBG Forschungs GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent for all study procedures including an additional core biopsy after the first 4 cycles of EC must be obtained and documented according to the local regulatory requirements; - Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer the investigator has to decide prospectively which side will be evaluated for the primary endpoint; - 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. The following tumor stages are eligible: Locally advanced tumors with cT4 or cT3 or Tumors with cT2 cN+ In patients with multifocal or multicentric breast cancer, the largest lesion should be measured; - Age >= 18 years - Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment; - Negative HER-2/neu status - Karnofsky Performance status index >=80%; - Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to registration. Results must be above the normal limit of the institution and above 55%; - Laboratory requirements: (within 14 days prior to registration) Absolute neutrophile count (ANC) >= 2,0 x 10^9/L and Platelets >= 100 x 10^9/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 1,5 x UNL associated with alkaline phosphatase > 2,5 x UNL are not eligible for the study Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - 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. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intra uterine contraceptive devices, sterilization) during study treatment; - Pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI criteria; - 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 within past six months, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (systolic blood pressure >150 mm Hg or > 90 mmHg diastolic blood pressure under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease Thrombotic or embolic events including transient ischemic attacks within the past six months 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 including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent Major surgery, open biopsy or significant traumatic injury within 28 days of first dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: • to establish the most feasible regimen of EC-P (P-EC) with sorafenib ;Secondary Objective: Secondary objectives: • Safety of preoperative regimen • pCR rate at surgery • Determine clinical response rate • Histopathological axillary nodal status after neoadjuvant therapy • Correlate baseline and change in tumor and serum genetic, gene expression and proteomic patterns with clinical and pathological response ;Primary end point(s): The regimen with the highest cumulative dose of sorafenib. Any grade I-IV toxicity (CTCAE v3.0), treatment discontinuation, dose-modification. Any complete response in the breast and axilla defined as no invasive residuals documented according to histopathologic analyses of tumor samples after neoadjuvant and Sorafenib therapy at time of surgery. Any response (complete, partial response) or status of stable disease after sorafenib therapy according to WHO criteria. Any complete response documented according to histopathologic analyses of axillary nodal samples after neoadjuvant and Sorafenib therapy at time of surgery (ypN0) irrespective of the residuals in the breast. Analysis of tumor samples obtained before, during and after neoadjuvant and Sorafenib therapy. | — |
Countries
Germany
Outcome results
None listed