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

NCT ID: NCT03300557

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-15
• Study Completion Date: 2025-08-14

Brief Summary

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.

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.

Conditions

Atypical Hyperplasia; Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia; Endometrial Carcinoma; FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Exemestane

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pharmacokinetic Study

Intervention Type: OTHER

Correlative studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Exemestane

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pharmacokinetic Study

Correlative studies

Intervention Type: OTHER

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

Aromasin; FCE-24304; PHARMACOKINETIC; PK Study

Eligibility Criteria

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)

• Minimum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Britt K Erickson

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

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

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2017-01782

Identifier Type: REGISTRY

Identifier Source: secondary_id

UW17010

Identifier Type: -

Identifier Source: secondary_id

N01-CN-2012-00033

Identifier Type: -

Identifier Source: secondary_id

2016LS183 / UWI17010/UAB1788

Identifier Type: OTHER

Identifier Source: secondary_id

UWI2016-08-01

Identifier Type: OTHER

Identifier Source: secondary_id

N01CN00033

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014520

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2017-01782

Identifier Type: -

Identifier Source: org_study_id