Megestrol in Treating Patients With Endometrial Neoplasia or Endometrial Hyperplasia

High Grade Squamous Intraepithelial Neoplasia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00503581
• Other study ID #: GOG-0224
• Secondary ID: NCI-2009-00594GO
• Status: Terminated
• Phase: Phase 2
• Start date: July 2007

Study information

• Verified date: October 2020
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma in Situ
• Endometrial Hyperplasia
• High Grade Squamous Intraepithelial Neoplasia
• Hyperplasia
• Neoplasms
• Stage 0 Uterine Corpus Cancer

Intervention

Procedure:
• Biopsy
Undergo biopsy

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Megestrol Acetate
given orally

Other:
• Pharmacological Study
Correlative studies
• Quality-of-Life Assessment
Ancillary studies

Procedure:
• Therapeutic Conventional Surgery
undergo hysterectomy

Locations

Country	Name	City	State
United States	Saint Anthony's Health	Alton	Illinois
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	State University of New York Downstate Medical Center	Brooklyn	New York
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Northwestern University	Chicago	Illinois
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Gynecologic Oncology of West Michigan PLLC	Grand Rapids	Michigan
United States	Hartford Hospital	Hartford	Connecticut
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois
United States	Community Howard Regional Health	Kokomo	Indiana
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Columbia Saint Mary's Water Tower Medical Commons	Milwaukee	Wisconsin
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Michiana Hematology Oncology PC-Niles	Niles	Michigan
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	FirstHealth of the Carolinas-Moore Regional Hosiptal	Pinehurst	North Carolina
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Lakeland Hospital	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Memorial University Medical Center	Savannah	Georgia
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium CCOP	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield	Springfield	Missouri
United States	Olive View-University of California Los Angeles Medical Center	Sylmar	California
United States	Cancer Care Associates-Midtown	Tulsa	Oklahoma
United States	Tulsa Cancer Institute	Tulsa	Oklahoma
United States	Carle Clinic-Urbana Main	Urbana	Illinois
United States	Michiana Hematology Oncology-PC Westville	Westville	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Who Experience a Response as Determined by a Central Blinded Review of the Three Post Treatment Endometrial	Treated and eligible participants. This study had 0 participants that completed treatment, therefore no analysis was done. Study closed prior to completion. Central blinded review was not performed for any participants in the study.	Up to 12 months after completion of treatment
Secondary	Change in Quality of Life (QOL) Evaluated Using the Hospital Anxiety and Depression Scale (HADS) and the Two Items on Bleeding and Weight Gain	Eligible and Treated patients. This study had 0 participants that completed study.	Baseline to up to 12 months