Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

Conditions:Breast Cancer, Cancer, Cancer, Postmenopausal Syndrome, Women's Studies
Therapuetic Areas:Endocrinology, Oncology, Reproductive
Age Range:Any - 75
Start Date:December 6, 2016

Use our guide to learn which trials are right for you!

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

This randomized phase IIb trial studies how well alternative dosing of exemestane before
surgery works in treating in postmenopausal patients with stage 0-II estrogen positive breast
cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming
back. The use of exemestane may treat early stage (stage 0-II) breast cancer. Comparing the
exemestane standard dose regimen versus two alternative, less frequent dose regimens may
decrease undesirable symptoms and have similar efficacy in reducing serum estradiol.


I. 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.


I. To assess safety and toxicity. II. To support the preventive activity of exemestane we
will investigate the change in Ki-67 and progesterone receptor (PgR) levels in tumor cells
and the adjacent intraepithelial neoplasia or benign histologic structures.

III. To assess possible association of estradiol level with tissue and circulating

IV. To investigate possible pharmacogenetic markers. V. To assess drug levels on tissue
samples. VI. To investigate tissue and circulating proteomics profiling.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive exemestane orally (PO) once daily (QD) on days 1-7.

ARM II: Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo
PO QD on days 2, 4, 6, and 7.

ARM III: Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7.

In all arms, courses repeat every 7 days for 4-6 weeks in the absence of disease progression
or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.

After completion of study treatment, patients are followed up at 20-30 days.

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] in the menopausal levels as per local institutional guidelines if < 60
years old) with histologically-confirmed estrogen receptor (ER)-positive (>= 10%)
primary breast cancer stage cT0-2, cN0-1, Mx; women with larger tumors who refuse
chemotherapy (chemo) and/or endocrine neoadjuvant therapy can be eligible

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

- Leukocytes >= 3,000/microliter

- Absolute neutrophil count >= 1,500/microliter

- Platelets >= 100,000/microliter

- Total bilirubin =< 2 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 1.5 x institutional ULN

- Serum creatinine =< 1.5 times institutional ULN

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Body mass index (BMI) < 18.5 Kg/m^2

- Previous treatment for breast cancer including chemotherapy, endocrine therapy and
radiotherapy; women with prior ductal breast carcinoma in situ (DCIS) who were treated
with surgery only and whose treatment ended >= 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 invasive 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 systemic hormone replacement therapy (HRT) in the last 30 days prior to the
randomization; the use of non-systemic estrogen (such as vaginal estrogen use) is

- Use of any chemopreventive agents (selective estrogen receptor modulators [SERM]) in
the last 3 months

- Concomitant use of CYP3A4 inducer medication (rifampicin, phenytoin, carbamazepine,
phenobarbital, and St. John's wort)
We found this trial at
New York, New York 10032
Principal Investigator: Katherine D. Crew
Phone: 212-305-1732
New York, NY
Click here to add this to my saved trials
Genoa, 16128
Principal Investigator: Andrea Decensi
Phone: 39-010 5634501
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Powel H. Brown
Phone: 713-792-4509
Houston, TX
Click here to add this to my saved trials
Tampa, Florida 33612
Principal Investigator: Nagi B. Kumar
Phone: 813-745-6885
Tampa, FL
Click here to add this to my saved trials