Clinical Trials /

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

NCT03300557

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.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Exemestane in Treating Patients With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer
  • Official Title: Pilot Study of Daily Exemestane in Women With Complex Atypical Hyperplasia of the Endometrium / Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-01782
  • SECONDARY ID: NCI-2017-01782
  • SECONDARY ID: UW17010
  • SECONDARY ID: N01-CN-2012-00033
  • SECONDARY ID: 2016LS183 / UWI17010/UAB1788
  • SECONDARY ID: UWI2016-08-01
  • SECONDARY ID: N01CN00033
  • SECONDARY ID: P30CA014520
  • NCT ID: NCT03300557

Conditions

  • Atypical Hyperplasia
  • Endometrial Intraepithelial Neoplasia
  • FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
  • FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma

Interventions

DrugSynonymsArms
ExemestaneAromasin, FCE-24304Treatment (exemestane)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (exemestane)ExperimentalPatients 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.
  • Exemestane

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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:45 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in tumor proliferation
Time Frame:Baseline up to 7 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Changes in circulating serum estradiol
Time Frame:Baseline up to 7 months
Safety Issue:
Description:
Measure:Changes in circulating serum progesterone
Time Frame:Baseline up to 7 months
Safety Issue:
Description:
Measure:Pathological response to exemestane
Time Frame:Up to 7 months
Safety Issue:
Description:Will assess regression of complex atypical hyperplasia/endometrial intraepithelial neoplasia and low grade (grade 1 and grade 2) endometrial carcinoma.
Measure:Tissue marker analysis
Time Frame:Up to 7 months
Safety Issue:
Description:Will assess apoptosis (cleaved caspase 3), proliferation (cyclin D1), insulin pathway (pAKT, IGF-1R), and endocrine regulation (estrogen receptor/progesterone receptor/androgen receptor).
Measure:Deoxyribonucleic acid (DNA) mutational analysis
Time Frame:Up to 7 months
Safety Issue:
Description:Will be analyzed by next generation sequencing.
Measure:Methylation status of endometrial tumor
Time Frame:Up to 7 months
Safety Issue:
Description:
Measure:Protein and DNA markers
Time Frame:Up to 7 months
Safety Issue:
Description:Will be assessed via tampon recovery pre and post exemestane treatment.
Measure:Ki-67 expression
Time Frame:Up to 7 months
Safety Issue:
Description:Will compare Ki-67 expression between participants samples and historically matched samples.
Measure:Plasma levels of exemestane
Time Frame:Up to 7 months
Safety Issue:
Description:Will evaluate plasma levels of exemestane pre and post treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

December 9, 2019