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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endometrial Neoplasms

Uterine Neoplasms

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Ovarian Diseases

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Genital Diseases, Female

Genital Diseases

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Medroxyprogesterone

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Contraceptives, Oral, Hormonal

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Contraceptive Agents, Hormonal

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Enzyme Inhibitors

Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.

Patients receive medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.

Hysterectomy

Laboratory Biomarker Analysis

Linda R Duska

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.

Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer

A Randomized Surgical Window Pilot Investigation of the Relationship of Short Term Medroxyprogesterone Acetate (NSC #26386) Compared to Medroxyprogesterone Acetate Plus Entinostat (NSC #706995) on the Morphologic, Biochemical, and Molecular Changes in Primary Endometrioid Adenocarcinoma of the Uterine Corpus

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.

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).

A response was defined as a decrease in Ki-67 protein expression in tumor from pre- to post-treatment.

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.

NRG Oncology

National Cancer Institute (NCI)

There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. No AEs were reported.

Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA

Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.

Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat

Total

30-49 years

50-59 years

60-69 years

70-99 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Participants with Endometrioid Cell Type Cancer

Linda Gedeon for Virginia Filiaci, PhD

Randomized, treated, evaluable specimen. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.

Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)

Randomized, treated, evaluable pre and post treatment specimen available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.

Percentage of Participants With a Histologic Response

Randomized, treated, evaluable pre and post treatment specimens available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer	NCT03018249	FIGO Grade 1 En... FIGO Grade 2 En... FIGO Grade 3 En...	Entinostat Hysterectomy Laboratory Biom... Medroxyprogeste...	18 Years -	National Cancer Institute (NCI)
Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer	NCT03018249	FIGO Grade 1 En... FIGO Grade 2 En... FIGO Grade 3 En...	Entinostat Hysterectomy Laboratory Biom... Medroxyprogeste...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for figo grade 3 endometrial endometrioid adenocarcinoma