Postmenopausal ER positive breast cancer, waiting for surgery. MedDRA version: 20.0 Level: LLT Classification code 10006190 Term: Breast cancer invasive NOS System Organ Class: 100000004864
Conditions
Interventions
Product Name: EXEMESTANE
Product Code: [EXEMESTANE]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EXEMESTANE
Current Sponsor code: EXEMESTANE
Concentration unit: mg milligram(s)
Concent
Sponsors
ISTITUTO EUROPEO DI ONCOLOGIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Postmenopausal women (postmenopausal: age >60 years, or amenorrhea = 12 months, or bilateral oophorectomy, or, in women with hysterectomy only, FSH in the menopausal levels as per local institutional guidelines if =65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: • BMI 2 years prior to enrollment are eligible for the trial. • Women who are planned to receive neoadjuvant therapy. • Participants may not be receiving investigational agents. • History of allergic reactions attributed to compounds of similar chemical or biologic composition to exemestane. • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. • Other co-existing malignancies (with the exclusion of basal cell carcinoma or skin squamous cell carcinoma) diagnosed during the last 2 years before randomization. • History of severe osteoporosis (T score < -4 either spine or hip), or presence of vertebral fracture • Use of HRT systemic in the last 30 days prior to the randomization. • Use of any chemopreventive agents (SERM) in the last 3 months. • Concomitant use of CYP3A4 inducer medication (rifampicin, phenytonin, carbamazepine, phenobarbital, and St. John’s wort)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Postmenopausal ER positive breast cancer, waiting for surgery.;Secondary Objective: To assess safety and toxicity. - To support the preventive activity of exemestane we will investigate the change in Ki-67 and PgR levels in tumor cells and the adjacent intraepithelial neoplasia or benign histologic structures. - To assess possible association of estradiol level with tissue and circulating biomarkers. - To investigate possible pharmacogenetic markers. - To assess drug levels on tissue samples. - To investigate tissue and circulating proteomics profiling. ;Primary end point(s): The primary endpoint is the percentage change of serum estradiol concentration from baseline and we will compare the median change and percentage changes among arms.;Timepoint(s) of evaluation of this end point: Enrollment period 24 months, treatment period 4-6 week. The analysis on the primary endpoint will be performed at the end of treatment completion of all participants. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Exemestane safety and toxicity will be evaluated at the clinic visit according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE) and by a self-administered Quality of Life questionnaire (MENQOL). • Change in Ki-67 expression comparing pre-treatment versus post-treatment specimen to compare the antiproliferative effect among the different dosages. • Serum drug measurements of exemestane and 17-dihydroxyexemestane at the end of treatment. • Additional validated method of estradiol measurement. This method has a lower detection limit (1 pg/ml) than the CLIA certified estradiol test (Quest) and will serve as a quality control since it has proven to more effectively detect estradiol concentrations at the very low level, which is characteristic of older postmenopausal women. • Serum concentrations of estrone, estrone-sulfate, will be measured by LC-MS/MS while androstenedione and testosterone will be measured by RIA. Sex hormone binding globulin serum levels will be measured by a chemiluminescent microparticle immunoassay (CMIA) on the ARCHITECT i System (Abbott Laboratories, Weisbaden, Germany). • Insulin and glucose concentrations will be measured with the Architect Immunoassay analyzer (Abbott Laboratories, Abbott Park, IL, US). • Adipokines: change in leptin and adiponectin serum concentrations will be analyzed and compared among the different treatments arms. These measurements will be performed by the use of commercially available enzyme linked immunoassays purchased from R&D systems (SPACE Import-Export Srl, Milan, Italy). • Measurement of breast tissue estradiol concentration in tumor and breast fat at time of surgery. • Centralized evaluation of ER, PgR, Her2 expression in tumor comparing pre-treatment levels (tru-cut biopsy) to post-treatment level expression (surgical specimen). Centralized evaluation of Ki-67 in adjacent intraepithelial neoplasia and or grossly benign tissue. • Drug measurements of exemestane and 17- | — |
Countries
Italy, United States
Contacts
Public ContactUfficio Studi Clinici e a Attività
Istituto Europeo di Oncologia
Outcome results
None listed