Study Title

A Randomized, Controlled Phase II Evaluation of Megestrol (MEGACE) in Different Dose and Sequence in the Treatment of Endometrial Intraepithelial Neoplasia (EIN) from Referred Cohort of Atypical Endometrial Hyperplasia (AEH) or EIN.

Study Objectives

• To determine the frequency of remission of atypical endometrial hyperplasia or endometrial intraepithelial neoplasia following treatment with continuous versus interrupted progestin therapy compared to no progestin treatment
• To determine the frequency of complete emission of endometrial intraepithelial neoplasia following treatment with continuous versus interrupted progestin therapy compared to no progestin treatment
• To evaluate the differences between the outcome assessments based on a re-evaluation endometrial biopsy done prior to hysterectomy and the hysterectomy specimen
• To evaluate whether endometrial thickness measured by ultrasound correlates with the hyperplasia or neoplasia or invasive cancer
• To examine tissue response to megestrol
• To examine hormone receptor (estrogen receptor and progesterone receptor) response to megestrol
• To examine patterns of serum protein and glycoprotein content associated with invasive cancer

Study Requirements

This study seeks to evaluate precancerous lesions of the endometrium with a 12-week course of a progestational agent in a continuous or cyclic treatment regimen prior to hysterectomy. Eligible patients will have an endometrial biopsy, a history and physical examination, blood tests, a transvaginal ultrasound, and a serum pregnancy test within defined time periods prior to enrollment in this study.

Patients with atypical endometrial hyperplasia or endometrial intraepithelial neoplasia will be randomized to one of the three following therapy groups in the study: Group 1 patients will take megestrol continuously for 12 weeks and then have a hysterectomy; Group 2 will take megestrol in an interrupted fashion for 12 weeks before having a hysterectomy; Group 3 patients will have a hysterectomy without any intervening treatment. Blood tests and an endometrial biopsy will be performed an intervals during the course of the study.

Inclusion Criteria

• Patients with a diagnosis of atypical endometrial hyperplasia or endometrial intraepithelial neoplasia diagnosed by D&C or endometrial biopsy
• Patients must have adequate hematologic, renal and hepatic function
• Patients of child-bearing potential must have a negative serum pregnancy test within 14 days of enrollment and must use appropriate non-hormonal contraception while participating in the study

Exclusion Criteria

• Patients with recognized endometrial carcinoma
• Patients who are considered inoperable
• Patients with current or prior history of breast cancer
• Patients with invasive malignancies
• Patients who have received prior radiotherapy or chemotherapy to any portion of the abdominal cavity or pelvis
• Patients who are pregnant or lactating
• Patients with a history of thrombophlebitis, thromboembolic phenomena or cerebrovascular disorders