randomized phase ii study of preoperative letrozole (femara) in combination with avastin in hormone receptor positive breast cancer

Conditions: Hormone-Sensitive Breast Cancer; Breast Cancer

Summary: 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.


Eligibility criteria:
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

Keywords: neoadjuvant treatment