Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer
Condition: Hormone-Sensitive Breast Cancer; Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Letrozole; Bevacizumab
Intervention description: Letrozole 2.5 mg po qd; bevacizumab 10 mg/kg IV
Intervention MeSH terms: Bevacizumab; Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoadjuvant treatment

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