Progestins for the Treatment of Endometrial Cancer or Precancers of the Uterus Before Surgery, The Pro-Window Trial

This phase II trial tests compares the effect of progestins, megestrol acetate to micronized progesterone, in treating patients with endometrial cancer and precancers of the uterus (atypical endometrial hyperplasia) before surgery. Progestins, similar to the natural hormone progesterone, are approved drugs used in birth control and hormone replacement pills, and some can treat uterine endometrial cancers. In the initial comparison of this rotating umbrella trial, megestrol acetate, a progestin, will be compared to micronized progesterone, a form of natural progesterone that is a hormone produced by body normally. Hormone therapy using megestrol acetate and micronized progesterone may be effective in treating patients with endometrial cancer or atypical endometrial hyperplasia before surgery, and understanding the tissue effects of each agent on the malignant endometrium will uncover novel mechanistic and biomarker data to understand how best to advanced hormone therapy for endometrial cancer.

PRIMARY OBJECTIVES: I. Perform an adaptive, master protocol, surgical window of opportunity rotating umbrella trial to assess the effectiveness of progestins in tissues from women with newly diagnosed endometrial cancer or atypical endometrial hyperplasia. II. Establish biomarkers and molecular signatures of progestin efficacy in patients with endometrial cancer. OUTLINE: Patients are randomized to 1 of 2 arms in the initial comparison. ARM I: Patients undergo biopsy or curettage and then receive megestrol acetate orally (PO) twice daily (BID) 21-24 days prior to standard of care (SOC) hysterectomy on study. ARM II: Patients undergo biopsy or curettage and then receive micronized progesterone PO once daily (QD) beginning 21-24 days prior to SOC hysterectomy on study. After completion of study treatment, patients are followed up at 30-45 days after surgery.