Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer

Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer

The purpose of this study is to evaluate the objective response rate of a combination of letrozole (Femara) and bevacizumab (Avastin) given preoperatively to postmenopausal patients with hormone sensitive breast cancer.

Inclusion Criteria:

• Histologically confirmed operable or potentially operable invasive breast adenocarcinoma that is clinically palpable and measurable
• Age ≥ 18 years
• Clinical Stage T2-4, N0-3, M0 (Stage II-III)
• Postmenopausal defined as Age ≥ 60 years and/or Age >45 years with amenorrhea 12 months with an intact uterus and/or History of bilateral oophorectomy and/or FSH and estradiol levels in postmenopausal range
• ECOG PS 0, 1
• Unifocal disease
• ER and/or PR positive
• Adequate hematological, renal, and hepatic functions Absolute neutrophil count ≥ 1,500/µL Platelet count ≥ 100,000/µL creatinine ≤ 1.5 mg/dL Serum total bilirubin ≤ 1.5 mg/dL Alkaline phosphatase ≤ 3X the ULN for the reference lab SGOT/SGPT ≤ 3X the ULN for the reference lab
• Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
• Use of effective means of contraception (men and women) in subjects of child-bearing potential

Exclusion Criteria:

• Prior history of and/or therapy for invasive breast cancer (includes chemotherapy, radiation, hormonal therapy including AIs, tamoxifen, raloxifene, fulvestrant or any other antiestrogen/SERM)
• Clinically significant cardiovascular disease, EF <50%
• Known CNS disease
• History of deep vein thrombosis or pulmonary embolism
• 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).
• Presence of non-healing wound or fracture
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• 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 (see Appendix E)
• History of myocardial infarction or unstable angina within 12 months prior to study enrollment
• Any history of stroke or transient ischemic attack at any time
• 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 Day 0
• Core biopsy or other minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
• Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential is mandatory
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
• Known hypersensitivity to any component of bevacizumab or letrozole
• Inability to comply with study and/or follow-up procedures