This pilot phase IIa trial studies how well exemestane works in treating patients with complex atypical hyperplasia of the endometrium/endometrial intraepithelial neoplasia or low grade endometrial cancer. Exemestane may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: I. To determine if there is a decrease in proliferation index, measured by Ki-67 expression, in complex atypical hyperplasia (CAH)/endometrial intraepithelial neoplasia (EIN) or low grade (grade 1 and grade 2) endometrial cancer cells from baseline to post-exemestane treatment. SECONDARY OBJECTIVES: I. Circulating serum estradiol and progesterone. II. Pathological response (regression of CAH/EIN or low grade \[grade 1 and grade 2\] endometrial carcinoma). III. Tissue biomarkers. IV. Deoxyribonucleic acid (DNA) mutational analysis through next generation sequencing and methylation status of endometrial tumor. V. Protein markers via tampon recovery before and after treatment. VI. DNA markers via tampon recovery. VII. Safety and adverse effects of treatment. VIII. Comparison of Ki-67 expression changes between study subjects and a historical cohort. IX. Evaluation of the levels of exemestane in the plasma samples pre and post treatment. OUTLINE: Patients receive exemestane orally (PO) once daily (QD) over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43. After completion of study treatment, patients with unresolved adverse events on day of surgery are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
40
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Change in Tumor Proliferation
Will be measured by change in Ki-67 expression. Will evaluate the change from baseline to post-exposure in absolute change in percent Ki-67 using one-sample Student's t-test or Wilcoxon signed-rank test, as appropriate.
Time frame: Baseline up to 2 months
Changes in Circulating Serum Estradiol
Circulating serum estradiol pre and post treatment to determine the effect of daily dose of 25mg of exemestane for 21-42 days.
Time frame: Baseline up to 2 months
Changes in Circulating Serum Progesterone
Circulating serum progesterone pre and post treatment to determine the effect of daily dose of 25mg of exemestane for 21-42 days.
Time frame: Baseline up to 2 months
Percent of Participants by Pathological Response Class at 2 Months
This measure assesses change in categories in pathological response. As pathological response is an ordered categorical variable with classes of No visible lesion, CAH/EIN, Grade I, Grade II, and Grade III in this study, a change in class from baseline to time of surgery represents a decrease or increase in disease severity.
Time frame: Up to 2 months
Change From Baseline in Percent of Cells Positive for Tissue Markers
Assessment of change from baseline for apoptosis (cleaved caspase 3), proliferation (cyclin D1), insulin pathway (pAKT, IGF-1R), and endocrine regulation (estrogen receptor/progesterone receptor/androgen receptor). The units for absolute change in is % Positive.
Time frame: Up to 2 months
Deoxyribonucleic Acid (DNA) Mutational Analysis
Will be analyzed by next generation sequencing.
Time frame: Up to 2 months
Protein Markers
Perform pre- and post-treatment proteomic analysis of vaginal proteins from tampon recovery to identify biomarkers that may predict response to exemestane treatment.
Time frame: Up to 2 months
Ki-67 Expression With Historic Controls
Will compare Ki-67 expression between participants samples and historically matched samples.
Time frame: Up to 2 months
Plasma Levels of Exemestane
Will evaluate plasma levels of exemestane pre and post treatment.
Time frame: Up to 2 months
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