A Phase II, Randomized, Open Label Trial of Pre-operative (Neoadjuvant)Letrozole (Femara) vs. Letrozole in Combination With Avastin in Post Menopausal Women With Newly Diagnosed Operable Breast Cancer
Inclusion Criteria:
All patients must meet the following criteria to be eligible for study entry:
- Pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of
the breast, T2-T3 / T4a-c / N0-2 / M0, with positive estrogen and/or progesterone
receptors, and Her-2-neu negative. Patients with inflammatory breast cancer will not
be included (T4d). Patients previously treated patients with no measurable disease
or patients with metastatic disease will be excluded.
- Give written informed consent prior to study specific screening procedures, with the
understanding that the patient has the right to withdraw from the study at any time,
without prejudice.
- Patients must be postmenopausal, defined as one of the following:
- Patients > 50 years of age with no spontaneous menses for at least 12 months,
- Bilateral oophorectomy
- Be ambulatory (outpatient) and have an ECOG PS <1.
- Patients must have measurable disease by mammogram and/or breast ultrasound (in
special cases a dedicated breast MRI may be clinically indicated). The target lesion
must not have been previously irradiated.
- No prior chemotherapy.
- Patients must have adequate organ and marrow function as defined as follows:
absolute neutrophil count > 1,500/mm3, hemoglobin > 8.0 g/dl, platelets > 75,000/mm3,
total bilirubin < 2 mg/dl, serum creatinine < 2 mg/dl, Transaminases (AST, ALT) may
be up to 2 x institutional upper limit of normal. In addition < 1 gr of protein in
24 hr urine collection and urine protein/creatinine ratio < 1.0.
- No life threatening parenchymal disease or rapidly progressing disease warranting
cytotoxic chemotherapy.
- Hypertension must be controlled (<150/100 mmHg).
- Ejection Fraction > 50% by echocardiogram. (LVEF greater than 75% at baseline should
be reviewed and/or the test repeated as it may be falsely elevated).
- No history of thrombosis during the previous 12 months.
Exclusion Criteria:
- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than this sponsor-investigator
Bevacizumab cancer study.
- Uncontrolled high blood pressure (>150/100 mmHg).
- Unstable angina
- New York Heart Association (NYHA) Grade III or greater congestive heart failure
- History of myocardial infarction or unstable angina within 12 months
- History of stroke or TIA within 12 months
- Clinically significant peripheral vascular disease
- History of a bleeding disorder
- Presence of central nervous system or brain metastases
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course
of the study
- Minor surgical procedures (excluding fine needle aspirations or core biopsies) within
5 days prior to Day 0
- Pregnant (positive pregnancy test) or lactating
- Urine protein: creatinine ratio greater than or equal to 1.0 at screening or patients
demonstrating > 1 gr of protein in 24 hr urine collection within 4 weeks prior to
study entry will not participate in the trial.
- 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
- Unwilling or unable to comply with the protocol for the duration of the study.
- Psychiatric illness/social situations that would limit compliance with study
requirements.
- History of another malignancy within the last five years except non-melanoma skin
cancer and carcinoma in-situ of uterine cervix.
- Patients with metastatic disease.