Browse EPPT > UWI2016-08-01
Exemestane in Treating Patients With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer

The following datasets contain the data available for EPPT UWI2016-08-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Files	Description
Data Dictionary (PDF - 612.5 KB)	1. The Enhanced Person dataset contains all relevant information from every dataset received (except the ae dataset). Each record represents one person and contains updated variable names, formats, and labels. All information coming from non-person-based datasets has been converted into a person-based format.
Data Dictionary (PDF - 61.8 KB)	2. The Adverse Events dataset contains adverse event information, including onset date, grade of severity, attribution to the study agent, and outcome. This version of the dataset includes updated variable names, formats, and labels.

Raw Datasets

These 37 datasets contain the raw form data received, excluding PII.

Show these datasets

Files	Description
Data Dictionary (PDF - 38.5 KB)	1. The Administration Intervention dataset contains intervention Administration
Data Dictionary (PDF - 56.6 KB)	2. The Adverse Events dataset contains adverse events that occurred during the study.
Data Dictionary (PDF - 40.7 KB)	3. The Agent Interruption dataset contains study agent interruption
Data Dictionary (PDF - 106.9 KB)	4. The Alcohol Questionnaire (Baseline) dataset contains alcohol baseline questionnaire
Data Dictionary (PDF - 46.0 KB)	5. The Alcohol Questionnaire (Follow-Up) dataset contains alcohol follow-up questionnaire
Data Dictionary (PDF - 50.3 KB)	6. The Baseline Symptoms dataset contains baseline symptoms
Data Dictionary (PDF - 42.0 KB)	7. The Blood Chemistry dataset contains blood chemistry results
Data Dictionary (PDF - 40.1 KB)	8. The Blood Hematology dataset contains blood hematology results
Data Dictionary (PDF - 40.1 KB)	9. The Blood Specimen Acquisition dataset contains blood samples
Data Dictionary (PDF - 38.2 KB)	10. The Clinical Pathology dataset contains clinical pathology
Data Dictionary (PDF - 47.7 KB)	11. The Compliance dataset contains study compliance
Data Dictionary (PDF - 42.3 KB)	12. The Concomitant Medications dataset contains concomitant medication
Data Dictionary (PDF - 46.5 KB)	13. The Exclusion Criteria V2 dataset contains exclusion criteria
Data Dictionary (PDF - 46.5 KB)	14. The Exclusion Criteria V3 dataset contains exclusion criteria
Data Dictionary (PDF - 46.5 KB)	15. The Exclusion Criteria V4 dataset contains exclusion criteria
Data Dictionary (PDF - 46.6 KB)	16. The Exclusion Criteria V5 dataset contains exclusion criteria
Data Dictionary (PDF - 40.4 KB)	17. The Inclusion Criteria V2 dataset contains inclusion criteria
Data Dictionary (PDF - 40.4 KB)	18. The Inclusion Criteria V3 dataset contains inclusion criteria
Data Dictionary (PDF - 40.4 KB)	19. The Inclusion Criteria V4 dataset contains inclusion criteria
Data Dictionary (PDF - 40.5 KB)	20. The Inclusion Criteria V6 dataset contains inclusion criteria
Data Dictionary (PDF - 39.0 KB)	21. The MDS dataset contains MDS
Data Dictionary (PDF - 37.3 KB)	22. The Medical And Surgical History (Baseline Section 1) dataset contains body systems normal and allergies
Data Dictionary (PDF - 31.9 KB)	23. The Medical And Surgical History (Baseline Section 2) dataset contains body system statuses
Data Dictionary (PDF - 31.4 KB)	24. The Medical And Surgical History (Baseline Section 3) dataset contains other body system statuses
Data Dictionary (PDF - 30.8 KB)	25. The Medical And Surgical History (Baseline Section 4) dataset contains diagnosis and date
Data Dictionary (PDF - 40.1 KB)	26. The Off Study dataset contains off study
Data Dictionary (PDF - 39.0 KB)	27. The Participant Contact dataset contains telephone contact
Data Dictionary (PDF - 45.4 KB)	28. The Physical Exam (Section 1) dataset contains physical exam ECOG
Data Dictionary (PDF - 37.9 KB)	29. The Physical Exam (Section 2) dataset contains physical exam of other body systems
Data Dictionary (PDF - 39.1 KB)	30. The Physical Exam (Section 3) dataset contains physical exam of body systems
Data Dictionary (PDF - 44.6 KB)	31. The Registration dataset contains registration
Data Dictionary (PDF - 42.1 KB)	32. The Screening dataset contains screening
Data Dictionary (PDF - 41.0 KB)	33. The Tissue Specimen Acquisition dataset contains tissue sample
Data Dictionary (PDF - 120.1 KB)	34. The Tobacco Questionnaire (Baseline) dataset contains tobacco baseline questionnaire
Data Dictionary (PDF - 103.6 KB)	35. The Tobacco Questionnaire (Follow-Up) dataset contains tobacco follow-up questionnaire
Data Dictionary (PDF - 33.2 KB)	36. The Verification dataset contains verication
Data Dictionary (PDF - 54.3 KB)	37. The Vital Signs dataset contains vitals

Trial 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.

Trial with one potential dose level:

• 25mg Exemestane daily for 21-42 days before surgery

Enrollment Statistics

Target Enrollment: 40

Total Enrollment: 46

• 40 people were at dose level 1: 25mg Exemestane (40 of 46)
  • 40 people completed the study
• 6 people did not participate in study (6 of 46)
  • 6 people were ineligible

Total Study Population Demographics:

• Age:
• Mean: 63
• SD: 6.4
• Self-identified race:
• White: 39 (97.5%)
• Asian: 1 (2.5%)
• Black: 0 (0%)
• Self-identified ethnicity:
• Non-Hispanic: 40 (100%)
• Hispanic: 0 (0%)
• BMI:
• Mean: 40.3
• SD: 9.8
• Preoperative diagnosis:
• EIN/CAH: 11 (27.5%)
• Grade 1: 26 (65%)
• Grade 2: 3 (7.5%)

Eligibility Criteria

Inclusion Criteria

1. 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
2. No prior treatment for CAH/EIN/EC
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
5. Hemoglobin ≥ 9 g/dL
6. Serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5 × institutional upper limit of normal (ULN)
7. Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ 1 x ULN
8. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
9. White blood cell (WBC) ≥ 3000/mcl
10. Platelets ≥ 100,000/mcl
11. Able and willing to take oral medications
12. Ability to understand and the willingness to sign a written informed consent document
13. Body mass index (BMI) > 20

Exclusion Criteria

1. 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)
2. Not a surgical candidate or surgery is not scheduled within 43 days from starting the study drug
3. Receiving any other investigational agents
4. Any gastrointestinal condition causing malabsorption or obstruction (e.g. celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome)
5. 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
6. 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
7. 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
8. Known hypersensitivity to exemestane or its excipients
9. Known intercurrent illness or psychiatric illness/social situations that will limit compliance with study requirements
10. Evidence or high suspicion of metastatic disease at enrollment
11. 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)
12. 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)

Schema

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Results/Findings:

Thirty-eight participants had evaluable specimens for both pre- and post-treatment Ki-67 analysis. There was no tissue available for analysis for two participants. Median Ki-67 score decreased from 40.7% [IQR (33.9, 50.3)] at baseline to 18.1% [IQR (8.8, 31.8)] after exemestane treatment. This represents a median absolute change from baseline of -20.4% [IQR (-29.9, -6.7), P < 0.001]. In total, the percentage of Ki67 in tumor cells declined in 31 participants and increased in seven participants. There were no outstanding features identified for the participants in whom Ki-67 increased. Specifically, compliance with dosing, tumor grade, BMI, and ER/PR positivity in those with increased Ki-67 was similar to that of the entire cohort. Age and BMI were not associated with the change in Ki-67. Preoperative diagnosis was correlated with Ki-67 decrease, with greater decreases seen in participants with CAH/EIN and grade 1 tumors compared with grade 2 tumors (r = 0.38, P = 0.019).