A Phase III, Multicenter, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy Regimens in Subjects With Previously Treated Metastatic Breast Cancer
- Signed informed consent form.
- ≥ 18 years of age.
- Histologically confirmed carcinoma of the breast with measurable or non-measurable
metastatic disease that has progressed (patients with a history of brain metastasis
are eligible for study participation [USA only], as long as their brain metastases
have been treated and they have no evidence of progression or hemorrhage after
treatment and no ongoing requirement for dexamethasone).
- Progression of disease during or following administration of one
(non-investigational) chemotherapy regimen administered in the first-line setting.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- For women of childbearing potential, use of an effective means of non-hormonal
- Life expectancy ≥ 3 months.
- Willingness and capacity to comply with study and follow-up procedures.
- Prior hormonal therapy only as treatment for metastatic disease without chemotherapy.
Patients must have received chemotherapy for their metastatic disease in the
first-line setting. Hormone therapy alone is not allowed.
- For subjects who have received prior anthracycline-based therapy, documentation of
left ventricular ejection fraction < 50% by either multiple gated acquisition (MUGA)
or echocardiogram (ECHO).
- Treatment with more than one prior cytotoxic regimen for metastatic breast cancer
- HER2-positive status (patients who have unknown HER2 status, and for whom
determination of HER2 status is not possible, are eligible for this study).
- Unknown estrogen receptor (ER) and progesterone receptor (PR) status.
- Radiation therapy other than for palliation or brain metastasis, biologic therapy, or
chemotherapy for MBC within 21 days prior to Day 0 (Day 1 of Cycle 1 of treatment).
- Prior therapy with bevacizumab or other vascular endothelial growth factor (VEGF)
- Untreated brain metastasis.
- Inadequately controlled hypertension.
- Unstable angina.
- New York Heart Association Grade II or greater congestive heart failure (CHF).
- History of myocardial infarction within 6 months prior to Day 0 (the day of the first
- History of stroke or transient ischemic attack within 6 months prior to Day 0.
- Clinically significant peripheral vascular disease.
- Evidence of bleeding diathesis or coagulopathy.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0; anticipation of need for major elective surgical procedure during the
- Minor surgical procedures, fine-needle aspirations, or core biopsies within 7 days
prior to Day 0.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0.
- Serious, non-healing wound, ulcer, or bone fracture.
- History of anaphylactic reaction to monoclonal antibody therapy not controlled with
- History of other malignancies within 5 years of Day 0, except for tumors with a
negligible risk for metastasis or death, such as adequately controlled basal cell
carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- inadequate organ function.
- Pregnancy (positive serum pregnancy test) or lactation.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or renders the subject at high risk from treatment