Megestrol in Treating Patients With Endometrial Neoplasia or Endometrial Hyperplasia

NCT ID: NCT00503581

Last Updated: 2020-11-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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High Grade Squamous Intraepithelial Neoplasia Stage 0 Uterine Corpus Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Regimen 1 (megestrol acetate, surgery)

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.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Megestrol Acetate

Intervention Type DRUG

given orally

Pharmacological Study

Intervention Type OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

undergo hysterectomy

Regimen 2 (megestrol acetate, surgery)

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.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Megestrol Acetate

Intervention Type DRUG

given orally

Pharmacological Study

Intervention Type OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

undergo hysterectomy

Regimen 3 (surgery/biopsy)

(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.

Group Type ACTIVE_COMPARATOR

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

undergo hysterectomy

Interventions

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Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Megestrol Acetate

given orally

Intervention Type DRUG

Pharmacological Study

Correlative studies

Intervention Type OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Therapeutic Conventional Surgery

undergo hysterectomy

Intervention Type PROCEDURE

Other Intervention Names

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Bx 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate 17.alpha.-Acetoxy-6-methylpregna-4,6-diene-3,20-dione 6-Dehydro-6-methyl-17.alpha.-acetoxyprogesterone 6-Methyl-6-dehydro-17.alpha.-acetoxyprogesterone BDH 1298 BDH-1298 Maygace Megace Megestat Megestil Niagestin Ovaban Pallace SC-10363 Quality of Life Assessment

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Gynecologic Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Method

Role: PRINCIPAL_INVESTIGATOR

Gynecologic Oncology Group

Locations

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Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

Olive View-University of California Los Angeles Medical Center

Sylmar, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Site Status

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Site Status

Memorial University Medical Center

Savannah, Georgia, United States

Site Status

Saint Anthony's Health

Alton, Illinois, United States

Site Status

Rush - Copley Medical Center

Aurora, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Joliet Oncology-Hematology Associates Limited

Joliet, Illinois, United States

Site Status

Good Samaritan Regional Health Center

Mount Vernon, Illinois, United States

Site Status

Carle Clinic-Urbana Main

Urbana, Illinois, United States

Site Status

Elkhart Clinic

Elkhart, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Elkhart

Elkhart, Indiana, United States

Site Status

Elkhart General Hospital

Elkhart, Indiana, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Community Howard Regional Health

Kokomo, Indiana, United States

Site Status

IU Health La Porte Hospital

La Porte, Indiana, United States

Site Status

Franciscan Saint Anthony Health-Michigan City

Michigan City, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, United States

Site Status

Saint Joseph Regional Medical Center-Mishawaka

Mishawaka, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Plymouth

Plymouth, Indiana, United States

Site Status

Memorial Hospital of South Bend

South Bend, Indiana, United States

Site Status

Michiana Hematology Oncology PC-South Bend

South Bend, Indiana, United States

Site Status

South Bend Clinic

South Bend, Indiana, United States

Site Status

Northern Indiana Cancer Research Consortium CCOP

South Bend, Indiana, United States

Site Status

Michiana Hematology Oncology-PC Westville

Westville, Indiana, United States

Site Status

Gynecologic Oncology of West Michigan PLLC

Grand Rapids, Michigan, United States

Site Status

Michiana Hematology Oncology PC-Niles

Niles, Michigan, United States

Site Status

Lakeland Hospital

Saint Joseph, Michigan, United States

Site Status

Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Site Status

Southeast Missouri Hospital

Cape Girardeau, Missouri, United States

Site Status

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Site Status

Mercy Hospital Springfield

Springfield, Missouri, United States

Site Status

Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield

Springfield, Missouri, United States

Site Status

Saint Louis Cancer and Breast Institute-South City

St Louis, Missouri, United States

Site Status

Saint John's Mercy Medical Center

St Louis, Missouri, United States

Site Status

Saint Louis-Cape Girardeau CCOP

St Louis, Missouri, United States

Site Status

Women's Cancer Center of Nevada

Las Vegas, Nevada, United States

Site Status

State University of New York Downstate Medical Center

Brooklyn, New York, United States

Site Status

Montefiore Medical Center-Einstein Campus

The Bronx, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

FirstHealth of the Carolinas-Moore Regional Hosiptal

Pinehurst, North Carolina, United States

Site Status

Mount Carmel Health Center West

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Cancer Care Associates-Midtown

Tulsa, Oklahoma, United States

Site Status

Tulsa Cancer Institute

Tulsa, Oklahoma, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Columbia Saint Mary's Hospital - Ozaukee

Mequon, Wisconsin, United States

Site Status

Columbia Saint Mary's Water Tower Medical Commons

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2009-00594

Identifier Type: REGISTRY

Identifier Source: secondary_id

GOG-0224

Identifier Type: -

Identifier Source: secondary_id

CDR0000555427

Identifier Type: -

Identifier Source: secondary_id

GOG-0224

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0224

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0224

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA101165

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GOG-0224

Identifier Type: -

Identifier Source: org_study_id