Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer

This is an interventional treatment trial for Estrogen Receptor-negative Breast Cancer Read More

Inclusion Criteria:

• Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative (=< 10%), progesterone receptor (PR) negative (=< 10%) and human epidermal growth factor receptor 2 (HER2) normal (=< 10% of cells) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
• Be receiving first-line therapy for metastatic disease
• Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration
• OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL
• Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of 21 days prior to study treatment
• Bilirubin =< 1.5 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
• Alkaline phosphatase =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
• Platelets > 100,000 cells/mm^3
• Hemoglobin > 9.0 g/dL
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable
• If of childbearing potential must have a negative pregnancy test and use an effective method to avoid pregnancy for the duration of the trial and for at least 6 months after completion of study therapy
• Pre-existing peripheral neuropathy, if present, must be < grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version 3.0)
• Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional standards and federal guidelines

Exclusion Criteria:

• Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane
• Central nervous system (CNS) metastases that are symptomatic and/or requiring steroids
• Pre-existing nephritic syndrome
• Serious intercurrent medical or psychiatric illness including serious active infection
• 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 must have a UPC ratio done that is < 1.0 to be eligible; if the UPC ratio is >= 1.0 then the patient should undergo a 24-hour urine collection which must demonstrate =< 1 g of protein in 24 hours for the patient to be eligible)
• Known hypersensitivity to any component of bevacizumab or to nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation)