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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03018249
• Collaborator: NRG Oncology (Other)
• Enrollment: 50
• Locations: 234
• Arms: 2
• Actual Duration (Months): 41
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 3 Endometrial Endometrioid Adenocarcinoma	Drug: Entinostat; Procedure: Hysterectomy; Other: Laboratory Biomarker Analysis; Drug: Medroxyprogesterone Acetate	Early Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: Oct 11, 2017
• Actual Primary Completion Date: Apr 18, 2018
• Actual Study Completion Date: Mar 12, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (medroxyprogesterone acetate, hysterectomy) Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.	Procedure: Hysterectomy; Undergo hysterectomy; Other Names: Hysterectomy NOS ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Medroxyprogesterone Acetate; Given IM; Other Names: Amen Aragest Ciclotal Clinofem Clinovir Cycrin Depo-Clinovir Depo-Provera Depot-Medroxyprogestereone Acetate Farlutal G-Farlutal Gestapuran Hysron Lutoral Medroxyprogesterone 17-Acetate Medroxyprogesteroni Acetas Methylacetoxyprogesterone Metipregnone MPA Nadigest Nadigest (vet) Nidaxin Nidaxin (vet) Oragest Perlutex Prodasone Provera Sodelut G Veramix
Experimental: Arm II (medroxyprogesterone acetate, entinostat, hysterectomy) Patients receive medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.	Drug: Entinostat; Given PO; Other Names: HDAC inhibitor SNDX-275 MS 27-275 MS-275 SNDX-275 ; Procedure: Hysterectomy; Undergo hysterectomy; Other Names: Hysterectomy NOS ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Medroxyprogesterone Acetate; Given IM; Other Names: Amen Aragest Ciclotal Clinofem Clinovir Cycrin Depo-Clinovir Depo-Provera Depot-Medroxyprogestereone Acetate Farlutal G-Farlutal Gestapuran Hysron Lutoral Medroxyprogesterone 17-Acetate Medroxyprogesteroni Acetas Methylacetoxyprogesterone Metipregnone MPA Nadigest Nadigest (vet) Nidaxin Nidaxin (vet) Oragest Perlutex Prodasone Provera Sodelut G Veramix

Outcome Measures

Primary Outcome Measures

1. Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score) [Specimens were collected at hysterectomy on day 21-24 and analyzed in batch.]

   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.

Secondary Outcome Measures

1. Percentage of Participants With a Histologic Response [Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.]

   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).

2. Percent of Participants With a Ki67 Response [Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.]

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

3. The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE) [Up to 45 days after surgery]

   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.

Other Outcome Measures

1. Mean Post-treatment Tumor Estrogen Receptor Score [Up to 3 years]

2. Co-expression of PR, Ki67, and p21 [Up to 3 years]

   Will be compared between the arms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have a histologically proven diagnosis of endometrioid endometrial adenocarcinoma by endometrial curettage or biopsy within 8 weeks prior to registration; central pathology review will be required as part of the study but not for registration purposes

• History/physical examination within 42 +/- 5 days of planned surgical procedure (18-21 days from day 1); further protocol-specific assessments

• The trial is open only to women with primary endometrioid adenocarcinoma of the uterine corpus (all histologic grades and stages) who are planned and appropriate for primary surgical treatment to include removal of the uterine corpus via any surgical modality; the patient must be considered a suitable surgical candidate

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3 within 28 days prior to registration

• Formalin-fixed, paraffin-embedded tumor tissue from the biopsy or curettage must be submitted along with the corresponding pathology report

• Platelets >= 100,000/ul

• Granulocytes (ANC) >= 1,500/ul

• Creatinine =< 1.6 mg/dl

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limits of normal

• Bilirubin within institutional normal limits

• The patient must provide study-specific informed consent and authorization permitting release of personal health information prior to study entry

• Any patients of childbearing potential must have a negative pregnancy test

Exclusion Criteria:

• Patients with any non-endometrioid histology (such as serous, clear cell, or carcinosarcoma)

• Patients who have received prior progestin or anti-estrogen therapy during the 3 months before the diagnosis of endometrioid adenocarcinoma of the uterine corpus is established; estrogen therapy alone is allowed

• Patients with ECOG performance grade of 4

• Patients with history of thrombophlebitis within the past 2 years or ongoing thromboembolic disorders

• Patients who have previously received systemic, radiation or other treatment for uterine cancer

• Patients for whom formalin-fixed, paraffin-embedded tumor tissue from the biopsy or curettage is unavailable

• Patients must not have previously received a non Food and Drug Administration (FDA) approved histone deacetylase (HDAC) inhibitor in a clinical trial setting (entinostat, belinostat)

• Patients must not be currently taking or have ever taken vorinostat (Zolinza, Merck), panobinostat (Farydak, Novartis) or romidepsin (Istodax, Gloucester Pharmaceuticals)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas	United States	71913
2	John Muir Medical Center-Concord Campus	Concord	California	United States	94520
3	John Muir Medical Center-Walnut Creek	Walnut Creek	California	United States	94598
4	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
5	University of Colorado Hospital	Aurora	Colorado	United States	80045
6	Boulder Community Hospital	Boulder	Colorado	United States	80301
7	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
8	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
9	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
10	Denver Health Medical Center	Denver	Colorado	United States	80204
11	National Jewish Health-Main Campus	Denver	Colorado	United States	80206
12	The Women's Imaging Center	Denver	Colorado	United States	80209
13	Porter Adventist Hospital	Denver	Colorado	United States	80210
14	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
15	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
16	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
17	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
18	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
19	Rose Medical Center	Denver	Colorado	United States	80220
20	Mercy Medical Center	Durango	Colorado	United States	81301
21	Southwest Oncology PC	Durango	Colorado	United States	81301
22	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado	United States	80113
23	Swedish Medical Center	Englewood	Colorado	United States	80113
24	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
25	National Jewish Health-Western Hematology Oncology	Golden	Colorado	United States	80401
26	North Colorado Medical Center	Greeley	Colorado	United States	80631
27	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
28	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
29	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
30	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
31	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
32	Longmont United Hospital	Longmont	Colorado	United States	80501
33	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
34	McKee Medical Center	Loveland	Colorado	United States	80539
35	Parker Adventist Hospital	Parker	Colorado	United States	80138
36	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
37	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
38	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
39	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado	United States	80260
40	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
41	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
42	Beebe Medical Center	Lewes	Delaware	United States	19958
43	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
44	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
45	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
46	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
47	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
48	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware	United States	19973
49	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
50	Sacred Heart Hospital	Pensacola	Florida	United States	32504
51	Kootenai Medical Center	Coeur d'Alene	Idaho	United States	83814
52	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
53	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
54	Northwestern University	Chicago	Illinois	United States	60611
55	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
56	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois	United States	60045
57	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
58	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois	United States	60451
59	University of Chicago Medicine-Orland Park	Orland Park	Illinois	United States	60462
60	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
61	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
62	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
63	Alegent Health Mercy Hospital	Council Bluffs	Iowa	United States	51503
64	Greater Regional Medical Center	Creston	Iowa	United States	50801
65	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
66	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
67	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
68	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
69	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
70	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas	United States	66205
71	Flaget Memorial Hospital	Bardstown	Kentucky	United States	40004
72	Commonwealth Cancer Center-Corbin	Corbin	Kentucky	United States	40701
73	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky	United States	40504
74	Saint Joseph Hospital East	Lexington	Kentucky	United States	40509
75	Saint Joseph London	London	Kentucky	United States	40741
76	Jewish Hospital	Louisville	Kentucky	United States	40202
77	Saints Mary and Elizabeth Hospital	Louisville	Kentucky	United States	40215
78	Jewish Hospital Medical Center Northeast	Louisville	Kentucky	United States	40245
79	Jewish Hospital Medical Center South	Shepherdsville	Kentucky	United States	40165
80	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
81	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
82	Willis-Knighton Medical and Cancer Center	Shreveport	Louisiana	United States	71103
83	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
84	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
85	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
86	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
87	Unity Hospital	Fridley	Minnesota	United States	55432
88	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota	United States	55369
89	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
90	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
91	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
92	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
93	Health Partners Inc	Minneapolis	Minnesota	United States	55454
94	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
95	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
96	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
97	Regions Hospital	Saint Paul	Minnesota	United States	55101
98	United Hospital	Saint Paul	Minnesota	United States	55102
99	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
100	Lakeview Hospital	Stillwater	Minnesota	United States	55082
101	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
102	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
103	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
104	Fairview Lakes Medical Center	Wyoming	Minnesota	United States	55092
105	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri	United States	63011
106	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
107	Cox Cancer Center Branson	Branson	Missouri	United States	65616
108	Freeman Health System	Joplin	Missouri	United States	64804
109	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
110	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
111	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
112	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
113	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
114	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
115	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
116	CoxHealth South Hospital	Springfield	Missouri	United States	65807
117	Mercy Hospital Washington	Washington	Missouri	United States	63090
118	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
119	Billings Clinic Cancer Center	Billings	Montana	United States	59101
120	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
121	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
122	Great Falls Clinic	Great Falls	Montana	United States	59405
123	Saint Peter's Community Hospital	Helena	Montana	United States	59601
124	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
125	Community Medical Hospital	Missoula	Montana	United States	59804
126	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
127	Heartland Hematology and Oncology	Kearney	Nebraska	United States	68845
128	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
129	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska	United States	68510
130	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
131	Hematology and Oncology Consultants PC	Omaha	Nebraska	United States	68122
132	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
133	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
134	Creighton University Medical Center	Omaha	Nebraska	United States	68131
135	Midlands Community Hospital	Papillion	Nebraska	United States	68046
136	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
137	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
138	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
139	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
140	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
141	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
142	University of Rochester	Rochester	New York	United States	14642
143	Duke University Medical Center	Durham	North Carolina	United States	27710
144	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
145	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
146	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
147	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
148	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
149	TriHealth Cancer Institute-Westside	Cincinnati	Ohio	United States	45247
150	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio	United States	45255
151	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
152	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
153	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
154	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
155	Grant Medical Center	Columbus	Ohio	United States	43215
156	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
157	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
158	Doctors Hospital	Columbus	Ohio	United States	43228
159	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
160	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
161	Grady Memorial Hospital	Delaware	Ohio	United States	43015
162	Fairfield Medical Center	Lancaster	Ohio	United States	43130
163	OhioHealth Mansfield Hospital	Mansfield	Ohio	United States	44903
164	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
165	OhioHealth Marion General Hospital	Marion	Ohio	United States	43302
166	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
167	Licking Memorial Hospital	Newark	Ohio	United States	43055
168	Newark Radiation Oncology	Newark	Ohio	United States	43055
169	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
170	Saint Ann's Hospital	Westerville	Ohio	United States	43081
171	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
172	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
173	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
174	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
175	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
176	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania	United States	15009
177	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
178	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
179	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
180	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
181	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania	United States	15901
182	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
183	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
184	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania	United States	15132
185	UPMC-Coraopolis/Heritage Valley Radiation Oncology	Moon	Pennsylvania	United States	15108
186	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
187	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15213
188	UPMC-Saint Margaret	Pittsburgh	Pennsylvania	United States	15215
189	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
190	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
191	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania	United States	15237
192	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania	United States	15243
193	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania	United States	17901
194	Community Medical Center	Scranton	Pennsylvania	United States	18510
195	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania	United States	17870
196	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania	United States	16346
197	Geisinger Medical Group	State College	Pennsylvania	United States	16801
198	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania	United States	15401
199	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania	United States	15301
200	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
201	Women and Infants Hospital	Providence	Rhode Island	United States	02905
202	Prisma Health Cancer Institute - Laurens	Clinton	South Carolina	United States	29325
203	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
204	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
205	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
206	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
207	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
208	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
209	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
210	Prisma Health Cancer Institute - Spartanburg	Spartanburg	South Carolina	United States	29307
211	Memorial Hospital	Chattanooga	Tennessee	United States	37404
212	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee	United States	37067
213	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee	United States	37343
214	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee	United States	37204
215	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
216	Memorial GYN Plus	Ooltewah	Tennessee	United States	37363
217	Saint Joseph Regional Cancer Center	Bryan	Texas	United States	77802
218	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
219	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
220	Harrison Medical Center	Bremerton	Washington	United States	98310
221	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
222	Saint Elizabeth Hospital	Enumclaw	Washington	United States	98022
223	Saint Francis Hospital	Federal Way	Washington	United States	98003
224	Saint Clare Hospital	Lakewood	Washington	United States	98499
225	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
226	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
227	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
228	University of Washington Medical Center	Seattle	Washington	United States	98195
229	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington	United States	98405
230	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
231	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
232	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming	United States	82001
233	Billings Clinic-Cody	Cody	Wyoming	United States	82414
234	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Linda R Duska, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 20, 2018

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT03018249
• Other Study ID Numbers: NCI-2017-00058; NCI-2017-00058; NRG-GY011; NRG-GY011; NRG-GY011; U10CA180868
• First Posted: Jan 12, 2017
• Last Update Posted: Nov 16, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Adenocarcinoma; Carcinoma, Endometrioid; Medroxyprogesterone Acetate; Entinostat; Medroxyprogesterone; Histone Deacetylase Inhibitors

Study Results

Participant Flow

Recruitment Details	The study was open to accrual on 8/17/2017. The first patient was enrolled on October 11, 2017. The study closed to accrual 4 months later on 2/9/2018 after 50 patients were enrolled across 13 unique sites.

Arm/Group Title	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA	Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
Arm/Group Description	Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.	Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.
Period Title: Overall Study
STARTED	25	25
COMPLETED	23	23
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA	Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat	Total
Arm/Group Description	Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.	Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.	Total of all reporting groups
Overall Participants	25	25	50
Age, Customized (Count of Participants)
30-49 years	2 8%	2 8%	4 8%
50-59 years	7 28%	7 28%	14 28%
60-69 years	13 52%	13 52%	26 52%
70-99 years	3 12%	3 12%	6 12%
Sex: Female, Male (Count of Participants)
Female	25 100%	25 100%	50 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	25 100%	24 96%	49 98%
Unknown or Not Reported	0 0%	1 4%	1 2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 4%	2 8%	3 6%
White	23 92%	22 88%	45 90%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 4%	1 4%	2 4%
Participants with Endometrioid Cell Type Cancer (Count of Participants)
Count of Participants [Participants]	25 100%	25 100%	50 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA	Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
Arm/Group Description	Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.	Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.
Measure Participants	22	21
Mean (Standard Deviation) [units on a scale]	53.6 (64.8)	42.7 (49.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA, Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Percentage of Participants With a Histologic Response
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA	Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
Arm/Group Description	Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.	Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.
Measure Participants	22	20
Count of Participants [Participants]	16 64%	14 56%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA, Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; -25 to 30
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent of Participants With a Ki67 Response
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA	Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
Arm/Group Description	Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.	Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.
Measure Participants	22	20
Count of Participants [Participants]	15 60%	18 72%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA, Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.8
	Confidence Interval	(2-Sided) 95%; -16.7 to 45.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE)
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA	Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
Arm/Group Description	Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.	Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.
Measure Participants	23	23
Grade 1 AE	11 44%	9 36%
Grade 2 AE	4 16%	6 24%
Grade 3 AE	2 8%	2 8%
Grade 4 AE	0 0%	0 0%
Grade 5 AE	0 0%	0 0%

5. Other Pre-specified Outcome

Title	Mean Post-treatment Tumor Estrogen Receptor Score
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Co-expression of PR, Ki67, and p21
Description	Will be compared between the arms.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From initiation of treatment up to 45 days post-surgery
Adverse Event Reporting Description	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/Group Title	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA		Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
Arm/Group Description	Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.		Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.
All Cause Mortality
	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA		Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Serious Adverse Events
	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA		Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		1/23 (4.3%)
Blood and lymphatic system disorders
Thromboembolic Event	1/23 (4.3%)	1	1/23 (4.3%)	1
Skin and subcutaneous tissue disorders
Skin infection	0/23 (0%)	0	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA		Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/23 (60.9%)		16/23 (69.6%)
Blood and lymphatic system disorders
Anemia	3/23 (13%)		3/23 (13%)
Gastrointestinal disorders
Abdominal Pain	4/23 (17.4%)		8/23 (34.8%)
Constipation	5/23 (21.7%)		4/23 (17.4%)
Diarrhea	2/23 (8.7%)		4/23 (17.4%)
Dry Mouth	1/23 (4.3%)		2/23 (8.7%)
Nausea	2/23 (8.7%)		4/23 (17.4%)
General disorders
Edema Limbs	3/23 (13%)		2/23 (8.7%)
Fatigue	4/23 (17.4%)		8/23 (34.8%)
Injection Site Reaction	4/23 (17.4%)		5/23 (21.7%)
Pain	4/23 (17.4%)		4/23 (17.4%)
Investigations
Neutrophil Count Decreased	0/23 (0%)		2/23 (8.7%)
Platelet Count Decreased	0/23 (0%)		3/23 (13%)
Metabolism and nutrition disorders
Anorexia	2/23 (8.7%)		3/23 (13%)
Hypocalcemia	1/23 (4.3%)		2/23 (8.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/23 (8.7%)		1/23 (4.3%)
Nervous system disorders
Dysgeusia	0/23 (0%)		3/23 (13%)
Headache	3/23 (13%)		1/23 (4.3%)
Psychiatric disorders
Depression	0/23 (0%)		2/23 (8.7%)
Insomnia	1/23 (4.3%)		2/23 (8.7%)
Renal and urinary disorders
Urinary Incontinence	2/23 (8.7%)		0/23 (0%)
Reproductive system and breast disorders
Pelvic Pain	2/23 (8.7%)		2/23 (8.7%)
Vaginal Discharge	1/23 (4.3%)		4/23 (17.4%)
Vaginal Hemorrhage	1/23 (4.3%)		4/23 (17.4%)
Respiratory, thoracic and mediastinal disorders
Cough	1/23 (4.3%)		5/23 (21.7%)
Dyspnea	1/23 (4.3%)		5/23 (21.7%)
Skin and subcutaneous tissue disorders
Alopecia	1/23 (4.3%)		2/23 (8.7%)
Vascular disorders
Hypertension	1/23 (4.3%)		2/23 (8.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.