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.
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 Atypical Hyperplasia /Endometrioid Intraepithelial Neoplasia
- FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
- FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma
Interventions
Drug | Synonyms | Arms |
---|
Exemestane | Aromasin, FCE-24304 | Treatment (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
Name | Type | Description | Interventions |
---|
Treatment (exemestane) | Experimental | 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. | |
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)
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: | Active, not recruiting |
Lead Sponsor: | National Cancer Institute (NCI) |
Last Updated
July 14, 2021