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

Status: Active

Description

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.

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 (>= 60 years of age or with follicle stimulating hormone [FSH] > 30 IU/L if age 45-59); 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 Food and Drug Administration (FDA) 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)

Locations & Contacts

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: In review
Contact: Rebecca Christian Arend
Phone: 205-934-4986
Email: rarend@uabmc.edu

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Britt K. Erickson
Phone: 612-626-6283
Email: bkeric@umn.edu

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Howard H. Bailey
Phone: 608-263-8624
Email: hhb@medicine.wisc.edu

Italy

Genoa
Galliera Hospital
Status: Approved
Contact: Andrea De Censi
Phone: 39 010 5634501
Email: andrea.decensi@galliera.it

Trial Objectives and Outline

PRIMARY OBJECTIVES:

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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Britt K. Erickson

Trial IDs

Primary ID 2016LS183 / UWI17010/UAB1788
Secondary IDs UWI2016-08-01, NCI-2017-01782, N01-CN-2012-00033
Clinicaltrials.gov ID NCT03300557