A Randomized, Controlled Phase II Evaluation of Megestrol (Megace®) in Different Dose and Sequence in the Treatment of Endometrial Intraepithelial Neoplasia (EIN) From a Referred Cohort of Atypical Endometrial Hyperplasia (AEH) or EIN
- To determine the frequency of complete of remission of a community biopsy diagnosis of
atypical endometrial hyperplasia (AEH) or endometrial intraepithelial neoplasia (EIN)
at the time of hysterectomy in patients treated with continuous versus interrupted
- To determine the frequency of complete remission of central pathology panel diagnosed
EIN patients treated with continuous versus interrupted progestin therapy. (Patients
who did not receive progestin treatment closed to accrual as of 8/3/2010)
- To compare the quality-of-life (mood, concerns about weight, and bleeding) of patients
treated with these regimens.
- To assess the expression levels of PTEN in tumor tissue and its association with
response in patients treated with these regimens.
- To assess the expression levels of hormone receptors, estrogen and progesterone, in
tumor tissue, and their association with response in patients treated with these
- To assess histomorphometry and karyometry characteristics of pre-treatment biopsy in
- To identify patterns of protein and glycoprotein expression associated with invasive
cancer in serum specimens obtained from patients with a diagnosis of AEH or EIN.
- To assess differences in plasma concentrations of megestrol acetate among these
patients using high-performance liquid chromatography (HPLC).
- To assess patient compliance to their treatment regimen using HPLC to determine plasma
concentrations of megestrol.
- To explore the correlation between megestrol concentrations using HPLC and
pharmacodynamic response as assessed in hysterectomy specimens.
OUTLINE: Patients are stratified according to the collection method of the initial/intake
biopsy (dilatation and curettage vs all other methods). Patients are randomized to 1 of the
following treatment regimens:
- Regimen 1: Patients receive oral megestrol twice daily every day for 24 weeks.
Approximately twelve weeks after treatment starts, clinical blood tests are obtained
and research serum and plasma collected. Twenty-four weeks constitutes one course of
treatment and a pill count is performed during the 12-week f/u visit and at the
completion of the treatment course to determine compliance. After progestin therapy the
patient has an induced-withdrawal bleed. Patients in this arm undergo a re-evaluation
biopsy and hysterectomy a minimum of two weeks and a maximum of eight weeks after
completing the megestrol treatment.
- Regimen 2: Patients receive oral megestrol twice daily for two weeks continuously
followed by no treatment for two weeks. This course is repeated for a total of 24
weeks. Approximately twelve weeks after treatment starts, clinical blood tests are
obtained and research serum and plasma collected. Twenty-four weeks constitutes one
course of treatment and a pill count is performed during the 12-week f/u visit and at
the completion of the treatment course to determine compliance. After progestin therapy
the patient has an induced-withdrawal bleed. Patients in this arm undergo a
re-evaluation biopsy and hysterectomy a minimum of two weeks and a maximum of eight
weeks after the megestrol treatment.
- Regimen 3 (Closed as of 6/3/2010): Patients do not receive megestrol. At the discretion
of the managing physician, patients undergo the re-evaluation biopsy and hysterectomy
anytime between 2-20 weeks after enrollment and randomization.
Patients undergo biopsy and blood sample collection periodically for immunological and
pharmacodynamic studies. Samples are analyzed for presence or absence of myoinvasion or deep
myoinvasion in hysterectomy specimens, hormone receptivity status, and to compare PTEN
status against treatment via karyometry or morphometry, expression of VEGF and tenascin-C
(TN-C) via ELISA, presence of TN-C fragmentation via western immunoblots, additional
biomarkers via proteomic analysis, protein and glycoprotein expression patterns via
electrophoresis and image analysis, and plasma megestrol concentrations via high-performance
liquid chromatography (HPLC).
Patients complete the Hospital Anxiety and Depression Scale (HADS) and two items on bleeding
and weight gain at baseline and periodically during study. A Treatment Decision Assessment
is completed at baseline, and for patients withdrawing from the study, a Study Withdraw
Assessment is also completed.
There will be no additional follow-up on this study after the patient's hysterectomy.
Allocation: Randomized, Primary Purpose: Treatment
Number of patients who have responded to their respective treatment as determined by their re-evaluation biopsy and hysterectomy specimens
Michael W. Method, MD, MPH
Michiana Hematology-Oncology, PC - South Bend
United States: Federal Government
|George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus||New Britain, Connecticut 06050|
|Memorial Hospital of South Bend||South Bend, Indiana 46601|
|CCOP - Cancer Research for the Ozarks||Springfield, Missouri 65807|
|CCOP - Northern Indiana CR Consortium||South Bend, Indiana 46601|
|Saint Joseph Regional Medical Center||South Bend, Indiana 46617|
|St. John's Regional Health Center||Springfield, Missouri 65804|
|SUNY Downstate Medical Center||Brooklyn, New York 11203|
|Albert Einstein Cancer Center at Albert Einstein College of Medicine||Bronx, New York 10461|
|Oklahoma University Cancer Institute||Oklahoma City, Oklahoma 73104|
|Virginia Commonwealth University Massey Cancer Center||Richmond, Virginia 23298-0037|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|Elkhart General Hospital||Elkhart, Indiana 46515|
|Howard Community Hospital||Kokomo, Indiana 46904|
|Lakeland Regional Cancer Care Center - St. Joseph||St. Joseph, Michigan 49085|
|Cancer Care Associates - Saint Francis Campus||Tulsa, Oklahoma 74136-1929|
|Center for Cancer Therapy at LaPorte Hospital and Health Services||La Porte, Indiana 46350|
|Michiana Hematology-Oncology, PC - Elkhart||Elkhart, Indiana 46514|
|Elkhart Clinic, LLC||Elkhart, Indiana 46514-2098|
|Michiana Hematology Oncology PC - La Porte||La Porte, Indiana 46350|
|Michiana Hematology-Oncology, PC - South Bend||Mishawaka, Indiana 46545-1470|
|Michiana Hematology Oncology PC - Plymouth||Plymouth, Indiana 46563|
|Lakeside Cancer Specialists, PLLC||Saint Joseph, Michigan 49085|
|FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center||Pinehurst, North Carolina 28374|
|Duke Cancer Institute||Durham, North Carolina 27710|
|Women's Cancer Center - La Canada||Las Vegas, Nevada 89169|
|Olive View - UCLA Medical Center Foundation||Sylmar, California 91342|