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

Yale University

Status and phase: Terminated; Phase 2

Conditions: Breast Cancer; Hormone-Sensitive Breast Cancer

Treatments: Drug: Letrozole; Drug: Bevacizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00461773

0609001793

Details and patient eligibility

About

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.

Enrollment: 5 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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5 participants in 2 patient groups

bevacizumab

Active Comparator group

Description:

brief exposure bevacizumab

Treatment:

Drug: Bevacizumab

bevacizumab and letrozole

Active Comparator group

Description:

brief exposure bevacizumab and letrozole

Treatment:

Drug: Bevacizumab

Drug: Letrozole