Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer

• Status: Terminated
• Trial end date: 2010-05-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Collaborators: Genentech, Inc.; Novartis
• Treatments: Bevacizumab; Hormones; Letrozole

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