A Phase II Open Label Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination With Bevacizumab in Post-Menopausal Women With Newly Diagnosed Operable Breast Cancer
- Pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of
the breast, T2-T4 / T4a-c / N0-2 / M0, with positive estrogen and/or progesterone
receptors. Patients with inflammatory breast cancer will not be included (Stage
IIIb). Patients previously treated patients with no measurable disease or patients
with metastatic disease will be excluded.
- 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 (see Appendix B - consent form).
- Females 60 years of age (postmenopausal).
- Be ambulatory (outpatient) and have an ECOG PS <2 (Appendix F).
- Patients must have measurable disease by mammogram and/or breast ultrasound. 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 2.0 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%.
- No history of thrombosis during the previous year.
- 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 II or greater congestive heart failure see
- History of myocardial infarction within 6 months
- History of stroke within 6 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, fine needle aspirations or core biopsies within 7 days
prior to Day 0
- Pregnant (positive pregnancy test) or lactating
- Urine protein: creatinine ratio 1.0 at screening. 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 cured basal cell
carcinoma of skin and carcinoma in-situ of uterine cervix.
- Patients with metastatic disease.