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Megestrol in Treating Patients With Endometrial Neoplasia or Endometrial Hyperplasia

Information source: Gynecologic Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: High Grade Squamous Intraepithelial Neoplasia; Stage 0 Uterine Corpus Cancer

Intervention: Biopsy (Procedure); Laboratory Biomarker Analysis (Other); Megestrol Acetate (Drug); Pharmacological Study (Other); Quality-of-Life Assessment (Other); Therapeutic Conventional Surgery (Procedure)

Phase: Phase 2

Status: Terminated

Sponsored by: Gynecologic Oncology Group

Official(s) and/or principal investigator(s):
Michael Method, Principal Investigator, Affiliation: Gynecologic Oncology Group

Summary

This randomized phase II trial is studying how well megestrol works in treating patients with endometrial neoplasia or endometrial hyperplasia. Estrogen can cause the growth of endometrial cancer cells. Hormone therapy using megestrol may fight endometrial cancer by blocking the use of estrogen by the abnormal cells.

Clinical Details

Official title: A Randomized Phase II Evaluation of Continuous Progestin Therapy vs. Sequential Progestin Therapy in the Treatment of Endometrial Intraepithelial Neoplasia (EIN) From a Referred Cohort of Atypical Endometrial Hyperplasia (AEH) or EIN Patients That Desire Uterine Preservation

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Number of patients who experience a response as determined by a central blinded review of the three post treatment endometrial

Secondary outcome: Change in quality of life (QOL) evaluated using the Hospital Anxiety and Depression Scale (HADS) and the two items on bleeding and weight gain

Detailed description: PRIMARY OBJECTIVES: I. To determine the frequency of complete remission by a central pathology review panel in diagnosed endometrial intraepithelial neoplasia (EIN) patients treated for 24 weeks with oral continuous versus interrupted progestin therapy. SECONDARY OBJECTIVES: I. To evaluate whether quality of life is superior in patients who take continuous megestrol versus sequential megestrol by evaluating mood, concerns about weight changes and bleeding. TERTIARY: I. To assess the expression levels of PTEN using immunohistochemistry and to explore the association of PTEN expression levels with patient response to treatment. II. To assess the expression levels of the hormone receptors ER and PR using immunohistochemistry and to explore the association of ER/PR expression levels with patient response to treatment. III. To assess histomorphometry and karyometry characteristics of the pre-treatment biopsy in this patient population. IV. To identify patterns of protein and glycoprotein expression associated with invasive cancer in serum specimens obtained from patients with a diagnosis of atypical endometrial hyperplasia (AEH) or EIN. V. To assess differences in plasma concentrations of megestrol acetate HPLC in this patient population. VI. To assess patient compliance to their treatment regimen using HPLC. 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Patients must have a diagnosis of atypical endometrial hyperplasia (AEH) or

endometrial intraepithelial neoplasia (EIN) diagnosed by dilatation and curettage (D&C), Novak curettage, Vabra aspirate, or Pipelle endometrial biopsy at the enrolling institution within 12 weeks of enrollment

- Patients must desire uterine retention for duration of study (18 months or after 3rd

biopsy) if they remain EIN negative (-); patients are allowed to attempt pregnancy after their initial post-treatment biopsy without it being a major protocol violation

- Patients must have a GOG performance status of 0, 1, or 2

- White blood cell (WBC) >= 3000

- Platelets >= 100,000

- Granulocytes >= 1,500

- Creatinine =< 2

- Bilirubin =< 1. 5 x institutional upper limit normal

- Serum glutamic oxaloacetic transaminase (SGOT) =< 3 x institutional upper limit

normal

- Alkaline phosphatase =< 3 x institutional upper limit normal

- Patients of child-bearing potential must have a negative serum pregnancy test prior

to starting study drug and prior to each biopsy if capable of becoming pregnant (and at the discretion of the referring physician)

- Patients of childbearing potential must use appropriate non-hormonal contraception

while on study medication

- Patients who have met the pre-entry requirements

- Patients must have signed an approved informed consent and authorization permitting

release of personal health information Exclusion Criteria:

- Patients with a GOG performance status of 3 or 4

- Patients with recognized endometrial carcinoma

- Patients with current or prior history of breast cancer

- Patients with invasive malignancies, with the exception of nonmelanoma skin cancer

who had (or have) any evidence of the other cancer present within the past 5 years or whose previous cancer treatment contraindicates this protocol therapy

- Patients who have received prior radiotherapy to any portion of the abdominal cavity

or pelvis are excluded

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor are

excluded

- Patients who are pregnant or lactating

- Patients with a history of thrombophlebitis, thromboembolic phenomena, or

cerebrovascular disorders within the past 5 years

- Patients under 18 years of age

Locations and Contacts

Kaiser Permanente Los Angeles Medical Center, Los Angeles, California 90027, United States

Olive View-University of California Los Angeles Medical Center, Sylmar, California 91342, United States

Hartford Hospital, Hartford, Connecticut 06102, United States

Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, United States

The Hospital of Central Connecticut, New Britain, Connecticut 06050, United States

Memorial University Medical Center, Savannah, Georgia 31404, United States

Saint Anthony's Health, Alton, Illinois 62002, United States

Rush - Copley Medical Center, Aurora, Illinois 60504, United States

Northwestern University, Chicago, Illinois 60611, United States

Joliet Oncology-Hematology Associates Limited, Joliet, Illinois 60435, United States

Good Samaritan Regional Health Center, Mount Vernon, Illinois 62864, United States

Carle Clinic-Urbana Main, Urbana, Illinois 61801, United States

Elkhart Clinic, Elkhart, Indiana 46514-2098, United States

Elkhart General Hospital, Elkhart, Indiana 46515, United States

Michiana Hematology Oncology PC-Elkhart, Elkhart, Indiana 46514, United States

Indiana University/Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, United States

Community Howard Regional Health, Kokomo, Indiana 46904, United States

IU Health La Porte Hospital, La Porte, Indiana 46350, United States

Franciscan Saint Anthony Health-Michigan City, Michigan City, Indiana 46360, United States

Michiana Hematology Oncology PC-Mishawaka, Mishawaka, Indiana 46545, United States

Saint Joseph Regional Medical Center-Mishawaka, Mishawaka, Indiana 46545, United States

Michiana Hematology Oncology PC-Plymouth, Plymouth, Indiana 46563, United States

Memorial Hospital of South Bend, South Bend, Indiana 46601, United States

Michiana Hematology Oncology PC-South Bend, South Bend, Indiana 46601, United States

Northern Indiana Cancer Research Consortium CCOP, South Bend, Indiana 46628, United States

South Bend Clinic, South Bend, Indiana 46617, United States

Michiana Hematology Oncology-PC Westville, Westville, Indiana 46391, United States

Gynecologic Oncology of West Michigan PLLC, Grand Rapids, Michigan 49546, United States

Michiana Hematology Oncology PC-Niles, Niles, Michigan 49120, United States

Marie Yeager Cancer Center, Saint Joseph, Michigan 49085, United States

Lakeland Hospital, St. Joseph, Michigan 49085, United States

Saint Francis Medical Center, Cape Girardeau, Missouri 63703, United States

Southeast Missouri Hospital, Cape Girardeau, Missouri 63701, United States

Saint John's Mercy Medical Center, Saint Louis, Missouri 63141, United States

Saint Louis Cancer and Breast Institute-South City, Saint Louis, Missouri 63109, United States

Saint Louis-Cape Girardeau CCOP, Saint Louis, Missouri 63141, United States

Mercy Hospital Springfield, Springfield, Missouri 65804, United States

Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield, Springfield, Missouri 65804, United States

Women's Cancer Center of Nevada, Las Vegas, Nevada 89169, United States

Montefiore Medical Center-Einstein Campus, Bronx, New York 10461, United States

State University of New York Downstate Medical Center, Brooklyn, New York 11203, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

FirstHealth of the Carolinas-Moore Regional Hosiptal, Pinehurst, North Carolina 28374, United States

Mount Carmel Health Center West, Columbus, Ohio 43222, United States

University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States

Cancer Care Associates-Midtown, Tulsa, Oklahoma 74104, United States

Tulsa Cancer Institute, Tulsa, Oklahoma 74146, United States

Virginia Commonwealth University/Massey Cancer Center, Richmond, Virginia 23298, United States

Columbia Saint Mary's Hospital - Ozaukee, Mequon, Wisconsin 53097, United States

Columbia Saint Mary's Water Tower Medical Commons, Milwaukee, Wisconsin 53211, United States

Additional Information

Starting date: July 2007
Last updated: May 27, 2015

Page last updated: August 23, 2015

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