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
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,
- 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
- 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.
- 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
- 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.