Clinical trial NCT00503581
Conditions: High Grade Squamous Intraepithelial Neoplasia Stage 0 Uterine Corpus Cancer
Sponsor: Gynecologic Oncology Group
Start date: 2007-07-01; Completion date: 2012-07-01
Enrollment: 9 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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.

Arms: arm 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. arm 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. arm 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.
Interventions: intervention 1: Biopsy intervention 2: Laboratory Biomarker Analysis intervention 3: Megestrol Acetate intervention 4: Pharmacological Study intervention 5: Quality-of-Life Assessment intervention 6: Therapeutic Conventional Surgery
Intervention descriptions: intervention 1: Undergo biopsy intervention 2: Correlative studies intervention 3: given orally intervention 4: Correlative studies intervention 5: Ancillary studies intervention 6: undergo hysterectomy

Protocol documents: