a study evaluating the efficacy and safety of bevacizumab in combination with chemotherapy in untreated metastatic breast cancer (ribbon 1)

Conditions: Metastatic Breast Cancer

Summary: this is a phase iii, multicenter, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of bevacizumab in combination with chemotherapy compared with chemotherapy alone in subjects with previously untreated metastatic breast cancer.

this study includes a blinded treatment phase, an optional open-label post-progression phase, and a survival follow-up phase. during the blinded treatment phase, patients receive chemotherapy and study drug (bevacizumab or placebo) every 3 weeks until disease progression, treatment-limiting toxicity, or death due to any cause. the optional open-label post-progression phase consists of chemotherapy treatment (per investigator discretion) and optional treatment with open-label bevacizumab. patients who complete the study or who discontinue from treatment (regardless of participation in the optional open-label post-progression phase) will be followed for survival and subsequent anti-cancer therapies every 4 months until death, withdrawal of consent, loss to follow-up, or study termination. patients who discontinue from treatment during the blinded treatment phase for reasons other than disease progression will have tumor assessments every 9 weeks until documented disease progression or death.

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. * signed informed consent form. * age ≥ 18 years. * for women of childbearing potential, use of accepted and effective method of non-hormonal contraception. * eastern cooperative oncology group (ecog) performance status of 0 or 1. * ability and capacity to comply with study and follow-up procedures. * for anthracycline cohort only: adequate left ventricular function at study entry, defined as a left ventricular ejection fraction (lvef) ≥ 50% by either multigated acquisition (muga) scan scan or echocardiography (echo). * for subjects who have received recent radiation therapy, recovery prior to baseline (day 0) from any significant (grade ≥ 3) acute toxicity. exclusion criteria: * unknown human epidermal growth factor receptor 2 (her2) status or known her2-positive status. * prior chemotherapy for locally recurrent or metastatic disease. * prior hormonal therapy less than 1 week prior to day 0. * prior adjuvant or neoadjuvant chemotherapy within 12 months prior to day 0. * for anthracycline cohort only: prior anthracycline as part of neoadjuvant or adjuvant therapy for localized breast cancer. * investigational therapy within 28 days of day 0. * major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, or anticipation of need for major surgical procedure during the course of the study. * minor surgical procedures, such as fine needle aspirations or core biopsies, within 7 days prior to day 0. * prior therapy with bevacizumab, sorafenib, sunitinib, or other vascular endothelial growth factor (vegf) pathway-targeted therapy. * known brain or other central nervous system (cns) metastases. * blood pressure of \> 150/100 mmhg. * unstable angina. * new york heart association (nyha) grade ii or greater congestive heart failure (chf). * history of myocardial infarction within 6 months prior to day 0. * 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. * 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. * pregnancy (positive serum pregnancy test) or lactation. * inadequate organ function, as evidenced by any of the following laboratory values: absolute neutrophil count \ 1.5 mg/dl; alkaline phosphatase, ast, and/or alt \> 2x upper limit of normal (uln) (\> 5x uln in subjects with known liver or, for alkaline phosphatase elevations, bone involvement); alkaline phosphatase \> 2x uln (\> 7x uln in subjects with known bone involvement); serum creatinine \> 2.0 mg/dl; partial thromboplastin time (ptt) and/or either international normalized ratio (inr) or prothrombin time (pt) \> 1.5x upper limit of normal (except for subjects receiving anti-coagulation therapy); urine protein/creatinine ratio \> 1.0 at screening for u.s. subjects, or urine dipstick for proteinuria \>/= 1+ at screening followed by 24-hour urine collection demonstrating \> 1 g protein/24 hr for ex-u.s. subjects. * uncontrolled serious medical or psychiatric illness. * active infection requiring intravenous (iv) antibiotics at day 0. * 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 (subjects with a history of bilateral breast cancer will be eligible).