Bevacizumab and Abraxane as Second-line Therapy in Triple Negative Metastatic Breast Cancer

A Phase II Trial of Bevacizumab and ABI-007 (Abraxane) as Second-line Therapy in Her-2 Negative, Hormone Receptor Negative Metastatic Breast Cancer

The purpose of this study is to determine whether the addition of bevacizumab to Abraxane as second-line therapy in Her-2 negative, hormone receptor negative metastatic breast cancer.

Inclusion Criteria:

• Female, aged 18 years or older and able to give informed consent.
• Histologically- or cytologically-proven adenocarcinoma of the breast at time of first diagnosis
• ECOG performance status 0 or 1
• Life expectancy > 12 weeks
• Stage IV disease and have at least one lesion measurable by standard RECIST criteria
• Disease progression after at least one prior chemotherapy regimen for metastatic disease or within 12 months of adjuvant chemotherapy initiation.
• All chemotherapy must be stopped > 2 weeks before enrollment.
• Primary or metastatic tumor must be negative for estrogen and progesterone receptor expression. Testing must be done in a CLIA-approved laboratory.
• Primary or metastatic tumor must have 0 or 1+ staining for HER2/neu identified immunohistochemically (IHC), by an approved method using one of the standard monoclonal or polyclonal antibodies (HercepTest, cb-11, PAb1, or TAB250), or if FISH status is known, it must be negative. Testing must be done in a CLIA-approved laboratory.
• Left ventricular ejection fraction must be >= institutional lower limit of normal as determined by MUGA or echocardiogram
• Patient must be able to comply with treatment and follow-up procedures:
• Adequate bone marrow, liver and renal function; Absolute neutrophil count >= 1500/mm3; Hemoglobin >= 10 g/dl; Platelet count >= 100,000/mm3; Creatinine <= 2.0; PTT and either INR or PT < 1.5x normal; Total bilirubin <= 1.5 X upper limit of normal; AST, ALT, and alkaline phosphatase <= 2 X upper limit of normal (or <= 5X upper limit of normal if known liver metastases)
• If female is of childbearing potential, pregnancy test must be negative and patient must be willing to use effective contraception while on treatment and for at least 3 months after the last dose of study medication

Exclusion Criteria:

• Prior treatment with VEGF targeted therapy
• Prior taxane therapy for metastatic disease or for adjuvant therapy within the previous 12 months
• History of prior cancer, excluding carcinoma in situ of the cervix and non-melanoma skin cancers
• Known CNS disease
• Inadequately controlled hypertension (defined as systolic blood pressure>150 and/or diastolic blood pressure>100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
• Serious, non-healing wound, ulcer or bone fracture
• Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio >1.0 at screening OR Urine dipstick for proteinuria >2+ (patients discovered to have >2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1g of protein in 24 hours to be eligible)
• Patients with active infection
• Women who are pregnant or lactating
• Radiation therapy within 3 weeks of study entry
• Patients with hypersensitivity to ABI-007, Chinese hamster ovary cell products, or other recombinant human antibodies
• Baseline neuropathy > grade 2
• Participation in an investigational study of an antineoplastic agent within 4 weeks of first infusion of this study.