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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
Undergo biopsy
Undergo curettage
Undergo hysterectomy
Given PO
Given PO
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
RECRUITINGUniversity of New Mexico Cancer Center
Albuquerque, New Mexico, United States
RECRUITINGUniversity of Utah Sugarhouse Health Center
Salt Lake City, Utah, United States
NOT_YET_RECRUITINGUniversity of Virginia Cancer Center
Charlottesville, Virginia, United States
NOT_YET_RECRUITINGTissue response to progestin therapy
Will be determined by a change in the percentage in the expression of the proliferative marker Ki-67 comparing the pretreatment diagnostic biopsy to the posttreatment hysterectomy specimen. Immunohistochemical evaluation of Ki-67 protein expression will be determined as a continuous variable using the percent of cells staining positive in the nucleus
Time frame: From the time of pre treatment diagnostic biopsy to the time of post treatment hysterectomy specimen
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