Clinical Trial 18899

Cancer Type: Breast
Interventions:Aromasin (Exemestane); Exemestane

Study Type: Prevention
Phase of Study: Phase II
Investigators:

  • Nagi Kumar

Overview

Study Title

Alternative Dosing of Exemestane in Postmenopausal Women with Stage 0-II ER-Positive Breast Cancer: a Randomized Presurgical Trial

Summary

Exemestane has been approved as one of the treatments for breast cancer in postmenopausal women. It can be used for women whose breast cancer returns after treatment or as first treatment after surgery. Recently, exemestane has also been studied in healthy postmenopausal women to lower breast cancer risk. As part of this study, participants will receive exemestane, a medication that reduces estrogen levels. It is often taken daily by breast cancer patients after surgical removal of their tumors. The main goal of the study is to test whether giving a lower dose of this drug (by giving it less often than every day) can lower hormone levels as much as giving the drug daily and cause similar changes in breast cancers with fewer side effects.

Objective

Primary Objective: It has been shown that exemestane reduces estradiol levels both at the standard dose (25 mg/day) and at lower doses. We expect to achieve with 25 mg three times a week (M/W/F) and 25 mg/week similar effects in estradiol reductions to the standard dose of 25 mg daily. Non-inferiority of percent change in time of serum estradiol levels, adjusted for baseline levels, following four up to six weeks of exemestane 25 mg given three times per week or one time per week compared with exemestane 25 mg daily dosing. Secondary Objectives: - 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.

Inclusion Criteria

  • Postmenopausal women (postmenopausal: age >= 60 years, or amenorrhea >= 12 months, or bilateral oophorectomy, or in women with hysterectomy only follicle stimulating hormone [FSH] > 30 IU/L if less than 60 years old) with histologically confirmed estrogen receptor (ER) positive (>= 10%) primary breast cancer stage T(0-2), N(0-1), M(x); women with larger tumors who refuse chemotherapy (chemo) and/or endocrine neoadjuvant therapy can be eligible
  • Age less than or equal to 75 years
  • Eastern Cooperative Oncology Group (ECOG) performance status equal to or less than 1 (Karnofsky >= 70%)
  • Adequate organ and marrow function
  • Ability to understand and the willingness to sign a written informed consent document

  • Exclusion Criteria

  • Body mass index (BMI) less than 18.5 Kg/m^2
  • Previous treatment for breast cancer including chemotherapy and endocrine therapy
  • 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 coexisting 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 equal to or less than -4 either spine or hip), or presence of vertebral fracture
  • Use of hormone replacement therapy (HRT) in the last 30 days prior to the randomization
  • Use of any chemopreventive agents (selective estrogen receptor modulators [SERM]) in the last 3 months
  • Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer medication (rifampicin, phenytoin, carbamazepine, phenobarbital, and St. John's wort)