This randomized surgical window trial evaluates the effect of adding entinostat to medroxyprogesterone acetate before surgery works on progesterone receptors on endometrioid endometrial tumors. Medroxyprogesterone acetate is a progesterone, a hormone produced by body normally. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving medroxyprogesterone acetate with or without entinostat may effect tumors from endometrioid endometrial cancer.
PRIMARY OBJECTIVES: I. To determine whether the addition of the histone deacetylase inhibitor, entinostat, in combination with medroxyprogesterone acetate in the pre-operative setting results in up-regulation of activated progesterone receptors (PR) compared to medroxyprogesterone acetate alone. SECONDARY OBJECTIVES: I. To assess the response rate (as measured by cellular morphology and proliferation) and change in activated receptor levels with the addition of entinostat at the time of hysterectomy. OUTLINE: Two arms were randomly allocated to eligible patients with equal probability. ARM I: Patients receive medroxyprogesterone acetate intramuscularly (IM) on day 1 and undergo hysterectomy between days 21-24. ARM II: Patients receive medroxyprogesterone acetate IM on day 1 and entinostat orally (PO) on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
50
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas, United States
John Muir Medical Center-Concord Campus
Concord, California, United States
John Muir Medical Center-Walnut Creek
Walnut Creek, California, United States
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado, United States
University of Colorado Hospital
Aurora, Colorado, United States
Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)
The H-score is defined as the percent cells staining positive (0-100) multiplied by the staining intensity (0, 1, 2 or 3) measured in the tumor by immunohistochemistry and averaged over 3 reviewers. This score can range from 0 to 300. In general, PRs are expected to decrease in response to medroxyprogesterone acetate. It was hypothesized that entinostat would mitigate the decrease in PR relative to the medroxyprogesterone acetate only arm post treatment. Higher PR H-scores post treatment in the arm with entinostat relative to the medroxyprogesterone alone arm would be consistent with this hypothesis. Arm II was thought to result in higher scores which was expected to have a more favorable outcome when treated with MPA therapy.
Time frame: Specimens were collected at hysterectomy on day 21-24 and analyzed in batch.
Percentage of Participants With a Histologic Response
Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. A histologic response was defined as either the absence of identifiable adenocarcinoma in the hysterectomy specimen section (complete) or, subjectively, as the presence of a complex proliferation of glands that retain the architectural characteristics of adenocarcinoma, but with features of secretion, decreased nuclear stratification, or the presence of eosinophilic, squamous or mucinous metaplasia, when this was absent in the initial sample (partial).
Time frame: Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.
Percent of Participants With a Ki67 Response
A response was defined as a decrease in Ki-67 protein expression in tumor from pre- to post-treatment.
Time frame: Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.
The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE)
Maximum grade of physician assessed adverse events reported during treatment and up to 45 days after surgery. Grades start with 1 which is considered mild through grade 5 which is death. Participants on this study had adverse event grades up to grade 3 which is considered moderately severe.
Time frame: Up to 45 days after surgery
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Boulder Community Hospital
Boulder, Colorado, United States
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