Primary Outcome Measures:
- To evaluate the efficacy in terms of pathologic response of the combination of bevacizumab with docetaxel/cyclophosphamide followed by doxorubicin in women with operable/locally advanced breast cancer in the neo-adjuvant setting. [ Time Frame: upon surgery ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To evaluate clinical response in breast and the axillary lymph nodes after the completion of chemotherapy and bevacizumab. [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
- To evaluate the tolerability of the combination of bevacizumab with docetaxel/cyclophosphamide followed by doxorubicin in women with locally advanced breast cancer in the neo-adjuvant setting. [ Time Frame: periodically ] [ Designated as safety issue: Yes ]
- To evaluate the safety of bevacizumab given post operatively in the adjuvant setting for 6 months. [ Time Frame: 1 year after start of treatment ] [ Designated as safety issue: Yes ]
- To study the correlation of pathologic response with selected biological markers in the breast and lymph nodes. [ Time Frame: at surgery ] [ Designated as safety issue: No ]
- The data collected from this study, such as response rate and safety information, will help design a phase III trial for final testing of the benefit of bevacizumab in this population. [ Time Frame: upon study completion ] [ Designated as safety issue: No ]
Intervention Details:
Drug: Bevacizumab/Avastin
IV 15mg/kg 21 days
Drug: Cyclophosphamide
500mg per meter squared, IV every 21 days
Drug: Doxorubicin
60 mg per meter squared, IV every 21 days
Prior to being enrolled in this study, they will undergo an evaluation to determine eligibility. The study doctor will obtain a complete medical history, complete a physical examination including blood pressure and heart rate. The doctor will also obtain a baseline ECG as well as blood tests (approximately two tablespoons of blood). In order to decrease the effects of food, exercise and the sleep/wake cycle variability, all blood samples must be taken between 8AM - 10AM and patients will need to fast (no food or drink) for 10 hours prior to the blood test. Patients will also need to strain from working out prior to the blood test. The study will ask for a list of current medications. Patients will not be eligible if they have a history of or now require long-term anticoagulant (blood thinner) therapy (i.e. Coumadin or anything patients may be taking to prevent blood clots) have an allergy to bevacizumab or any other drugs used in the study.
Many of the following evaluations are commonly done to determine diagnosis and/or stage of breast cancer and may have already had some of all of them done. If the following procedures were not done within three weeks, they will need to be done again prior to receiving any study therapy.
- Diagnosis of breast cancer by fine needle aspiration or core needle biopsy will be required for entry in this study.
- Clip Placement - a clip will be placed in the tumor during the core biopsies as a marker to assist surgeons at the time of surgery.
- Tumor Clip Placements - a caliper is similar to a ruler and is used to measure the tumor from the outside of the body instead of always having to use an ultrasound or MRI.
- Tumor Ultrasound - this is a non-invasive exam that uses sound waves to produce a picture of your tumor.
All study participants will be treated with bevacizumab 15 mg/kg plus docetaxel 75 mg/m2 and cyclophosphamide 500 mg/m2 every three weeks for a total of four treatments. Three weeks after the completion of this part of the treatment patients will start receiving doxorubicin 60 mg/m2 every three weeks for a total of four treatments. All these drugs will be given as intravenous infusion on the first day of each three-week period.
Patients will come in for every three week visits and have a physical exam including blood pressure and heart rate. Medications lists will be taken and any side effects that may have been experienced. Tumor caliper measurements will be done and blood will be drawn at each of these visits.
A mammogram and MUGA scan will be done again just prior to surgery. Patients will undergo tumor surgery approximately six months after treatment. Patients will need to visit the study physician one month after surgery for another physical examination including blood pressure and heart rate, an assessment of any side effects and a list of current medications.