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

Yale University1 site in 1 country5 target enrollmentMarch 2007

ConditionsHormone-Sensitive Breast Cancer Breast Cancer

InterventionsBevacizumab Letrozole

DrugsLetrozole Bevacizumab

Overview

Phase: Phase 2
Intervention: Bevacizumab
Conditions: Hormone-Sensitive Breast Cancer
Sponsor: Yale University
Enrollment: 5
Locations: 1
Primary Endpoint: Number of Patients With Objective Tumor Response
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

March 2007

End Date

May 2010

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Yale University

Responsible Party

Sponsor

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)

Arms & Interventions

bevacizumab

brief exposure bevacizumab

Intervention: Bevacizumab

bevacizumab and letrozole

brief exposure bevacizumab and letrozole

Intervention: Letrozole

bevacizumab and letrozole

brief exposure bevacizumab and letrozole

Intervention: Bevacizumab

Outcomes

Primary Outcomes

Number of Patients With Objective Tumor Response

Time Frame: Up to 18 weeks

Clinical objective tumor response with 14 weeks of Neoadjuvant Letrozole combined with Bevacizumab was assessed using the following categories: Complete Response (CR): tumor is no longer visible. Partial response (PR): ≥ 50% decrease from baseline in the product of two perpendicular diameters, no new lesions. Progressive disease (PD): ≥ 25% increase of the product of two perpendicular diameters or new lesions. Stable Disease (SD): Neither CR, PR, or PD criteria met. Clinical tumor assessment was performed at baseline and every 2 weeks until week 18 prior to definitive surgery.