Clinical trial NCT00461773: Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer
Official title: Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hormone-Sensitive Breast Cancer
Breast Cancer
Keywords: Neoadjuvant treatment
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Novartis
name: Genentech, Inc.
First posted: 2007-04-18
Enrollment: 5
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Patients With Objective Tumor Response
timeFrame: Up to 18 weeks
Secondary outcomes:
measure: Breast Conservation
timeFrame: Up to 14 weeks
measure: Radiographic Tumor Response
timeFrame: 18 weeks
measure: Pathologic Complete Response
timeFrame: Up to 18 weeks
measure: Tumor Response With Biological Correlates
timeFrame: 2 weeks
measure: Drug Tolerability
timeFrame: Up to 18 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University, Yale Cancer Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Gina Chung, M.D.
role: PRINCIPAL_INVESTIGATOR
References: