Exemestane in Treating Patients With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer

Pilot Study of Daily Exemestane in Women With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer

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.

Study Overview

• Status: Completed
• Conditions: Endometrial Carcinoma; Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia; FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma; Atypical Hyperplasia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Other: Pharmacokinetic Study; Drug: Exemestane

Detailed Description

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
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females with a histologically proven CAH/ EIN or low grade (grade 1 or grade 2) endometrial carcinoma (EC) for which surgery is planned; the pathologic report from the referring facility will be used to determine pathologic eligibility; this report must be within 45 days of their baseline (pre-surgical) clinic visit
• No prior treatment for CAH/EIN/EC

• Post-menopausal confirmed with one the following criteria:

  • >= 60 years of age
  • Age 56 to 59 years of age with >= 2 years of amenorrhea
  • Age 56 to 59 years of age with < 2 years of amenorrhea and follicle stimulating hormone (FSH) within institutional post-menopausal range.
  • Age 45 to 55 years of age with FSH within institutional post-menopausal range. The Ki-67 expression changes based on menopausal status and specifically varies based on what phase of the menstrual cycle the sample is collected. Therefore, in order to eliminate this source of variability, only postmenopausal women will be included in this trial. In addition, exemestane is currently approved for use in post-menopausal women only.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Hemoglobin >= 9 g/dL
• Serum creatinine =< 1.5 x upper limit of normal or calculated creatinine clearance >= 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5 x institutional upper limit of normal (ULN)
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< 1 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• White blood cell (WBC) >= 3000/mcl
• Platelets >= 100,000/mcl
• Able and willing to take oral medications
• Ability to understand and the willingness to sign a written informed consent document
• Body mass index (BMI) > 20

Exclusion Criteria:

• Participants who had curatively treated invasive malignancies for which all treatments ended within 1 year prior to the study (with the exception of basal cell or squamous cell carcinoma of the skin)
• Not a surgical candidate or surgery is not scheduled within 43 days from starting the study drug
• Receiving any other investigational agents
• Any gastrointestinal condition causing malabsorption or obstruction (e.g. celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome)
• Has been on any hormonal treatment (including progestin-containing intrauterine device [IUD]) for CAH/EIN or low grade (grade 1 or grade 2) endometrial carcinoma in last 3 months
• Use hormone replacement therapy (including systemic or topical estrogen, progesterone, or testosterone based medication) or/and phytoestrogen supplements (i.e. black cohosh) or has been on progestin (including progestin containing IUD), tamoxifen or aromatase inhibitor within the prior 3 months
• Concomitant use of strong CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's wort as these may significantly reduce the availability of exemestane
• Known hypersensitivity to exemestane or its excipients
• Known intercurrent illness or psychiatric illness/social situations that will limit compliance with study requirements
• Evidence or high suspicion of metastatic disease at enrollment
• Women with severe bone density issues/osteoporosis (defined as any medical treatment for osteoporosis, and/or a T-score of -2.5 or lower, and/or history of fracture of the hip or spine)
• Unwilling or unable to undergo research biopsy during the baseline (pre-surgical) clinic visit, or inadequate research biopsy obtained during the baseline (pre-surgical) clinic visit (determined by the gynecologic oncologist at the time of the subject's pelvic exam)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (exemestane); Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Other: Pharmacokinetic Study; Correlative studies; Other Names: PHARMACOKINETIC; PK Study; Drug: Exemestane; Given PO; Other Names: Aromasin; FCE-24304

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Up to 2 months
Deoxyribonucleic Acid (DNA) Mutational Analysis	Will be analyzed by next generation sequencing.	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.	Up to 2 months
Ki-67 Expression With Historic Controls	Will compare Ki-67 expression between participants samples and historically matched samples.	Up to 2 months
Plasma Levels of Exemestane	Will evaluate plasma levels of exemestane pre and post treatment.	Up to 2 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Britt K Erickson, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): December 13, 2023
• Study Completion (Actual): August 14, 2025

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Endometrial Hyperplasia; Genetic Phenomena; Polymorphism, Genetic; Genetic Variation; exemestane; Pharmacogenomic Variants
• Other Study ID Numbers: NCI-2017-01782 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA014520 (U.S. NIH Grant/Contract); N01-CN-2012-00033; N01CN00033 (U.S. NIH Grant/Contract); UW17010; 2016LS183 / UWI17010/UAB1788 (Other Identifier: University of Wisconsin Carbone Cancer Center - University Hospital); UWI2016-08-01 (Other Identifier: DCP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No