Abraxane, Avastin, and Gemcitabine as First-Line Therapy for Patients With Metastatic Breast Cancer

This is a phase 2, single arm study. Participants will be treated with combination Gemzar, Abraxane and Avastin therapy until disease progression. Each treatment cycle is 28 days.

Inclusion criteria

• Patients must either be:

• treatment-naïve with newly diagnosed her2neu non-overexpressing (non amplified) metastatic (Stage IV) breast cancer, or
• HER2/neu-negative patients with metastasis diagnosed 6 or more months after completing primary systemic treatment (neoadjuvant, adjuvant chemotherapy).
• No previous chemotherapy regimen for metastatic breast cancer.
• 18 years of age or older.
• Measurable disease as defined by RECIST criteria or evaluable disease.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• Life expectancy greater than 3 months.
• For female (or male) patients, either pre- or post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control for the duration of the study
• Provide written informed consent before any study-related procedure not part of normal medical care is conducted
• Willing and able to comply with the protocol requirement
• Laboratory parameters as follows:

• Neutrophils: 1.5 x109/L or greater
• Platelets: 100 x109/L or greater
• Hemoglobin: ≥ 9.0 g/dL
• Serum Creatinine: ≤ 1.5mg/dL
• Bilirubin: ≤ ULN, except when caused by metastatic disease
• Alanine transaminase (ALT)/Aspartate transaminase (AST): ≤ 2.5 times the upper limit of the normal range (ULN) except when caused by metastatic disease
• Urine protein creatinine (UPC) ratio < 1.0 at screening.

Exclusion criteria

• Previous treatment with gemcitabine.
• History of Gastrointestinal Bleeding in the previous 3 months.
• Chemotherapy within 4 weeks prior to enrollment.
• Radiation therapy or evidence of acute effects of radiation therapy within 2 weeks prior to enrollment.
• Any major surgery within 4 weeks prior to enrollment.
• Presence of central nervous system or brain metastases.
• Urine protein: creatinine ratio ≥ 1.0 at screening.
• Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
• A prior history of hypertensive crisis or hypertensive encephalopathy.
• Peripheral neuropathy > grade I.
• Clinical AIDS or known positive HIV serology
• No concurrent clinically evident malignancy is allowed except inactive non-melanoma skin cancer and inactive cervical cancer diagnosed or other cancer for which the patient has been disease-free for five years.
• Unstable angina.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction within 6 months.
• History of stroke within 6 months.
• 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 enrollment, 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 enrollment.
• Pregnant (positive pregnancy test) or lactating.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment
• Serious, non-healing wound, ulcer, or bone fracture
• Inability to comply with study and/or follow-up procedures
• Participants with serious medical or psychiatric illness that would render chemotherapy unsafe are ineligible.
• Participants cannot have been in another experimental drug study other than a Bevacizumab cancer study within 4 weeks of the first infusion of these study medications.