Open Label Trial for Post-Menopausal Women With Newly Diagnosed Operable Breast Cancer
Open Label Trial for Post-Menopausal Women With Newly Diagnosed Operable Breast Cancer
The purpose of this study is to determine pathological response to a maximum of 18 weeks of
 neoadjuvant therapy using a combination of letrozole and Bevacizumab in post-menopausal women
 with pathologically confirmed invasive ductal cancer or invasive lobular cancer of the breast
 whose tumors are hormone positive.
This is an open label, single arm, and Phase II study of the combination of Letrozole and
 Bevacizumab in patients with newly diagnosed breast cancer. Patients meeting the eligibility
 criteria and who have signed the consent form will start Letrozole 2.5 mg by mouth a day and
 Bevacizumab 15 mg per Kg IV every 3 weeks for 18 weeks (24 weeks if still responding at week
 18 if approved by the PI). After neoadjuvant therapy, participants will undergo surgical
 treatment and will receive adjuvant therapy according to the treating physician.
Inclusion Criteria:

 -  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
 cytotoxic chemotherapy.

 -  Hypertension must be controlled (<150/100 mmHg).

 -  Ejection Fraction > 50%.

 -  No history of thrombosis during the previous year.

 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 II or greater congestive heart failure see
 Appendix G)

 -  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
 requirements.

 -  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.