Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03018249
Other study ID # NCI-2017-00058
Secondary ID NCI-2017-00058NR
Status Completed
Phase Early Phase 1
First received
Last updated
Start date October 11, 2017
Est. completion date March 12, 2021

Study information

Verified date November 2021
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 50
Est. completion date March 12, 2021
Est. primary completion date April 18, 2018
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility 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)

Study Design


Intervention

Drug:
Entinostat
Given PO
Procedure:
Hysterectomy
Undergo hysterectomy
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Medroxyprogesterone Acetate
Given IM

Locations

Country Name City State
United States Abington Memorial Hospital Abington Pennsylvania
United States Women's Cancer Care Associates LLC Albany New York
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States Community Hospital of Anaconda Anaconda Montana
United States Rocky Mountain Cancer Centers-Aurora Aurora Colorado
United States University of Colorado Hospital Aurora Colorado
United States Saint Louis Cancer and Breast Institute-Ballwin Ballwin Missouri
United States Greater Baltimore Medical Center Baltimore Maryland
United States Flaget Memorial Hospital Bardstown Kentucky
United States UPMC-Heritage Valley Health System Beaver Beaver Pennsylvania
United States Strecker Cancer Center-Belpre Belpre Ohio
United States Billings Clinic Cancer Center Billings Montana
United States Central Care Cancer Center - Bolivar Bolivar Missouri
United States Boulder Community Hospital Boulder Colorado
United States Rocky Mountain Cancer Centers-Boulder Boulder Colorado
United States Bozeman Deaconess Hospital Bozeman Montana
United States Cox Cancer Center Branson Branson Missouri
United States Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington
United States Harrison Medical Center Bremerton Washington
United States State University of New York Downstate Medical Center Brooklyn New York
United States Saint Joseph Regional Cancer Center Bryan Texas
United States Roswell Park Cancer Institute Buffalo New York
United States Highline Medical Center-Main Campus Burien Washington
United States Fairview Ridges Hospital Burnsville Minnesota
United States Christiana Care Health System-Concord Health Center Chadds Ford Pennsylvania
United States University of Virginia Cancer Center Charlottesville Virginia
United States Memorial Hospital Chattanooga Tennessee
United States Cheyenne Regional Medical Center-West Cheyenne Wyoming
United States Northwestern University Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States Adena Regional Medical Center Chillicothe Ohio
United States Bethesda North Hospital Cincinnati Ohio
United States Good Samaritan Hospital - Cincinnati Cincinnati Ohio
United States TriHealth Cancer Institute-Anderson Cincinnati Ohio
United States TriHealth Cancer Institute-Westside Cincinnati Ohio
United States Prisma Health Cancer Institute - Laurens Clinton South Carolina
United States Medical Oncology and Hematology Associates-West Des Moines Clive Iowa
United States Mercy Cancer Center-West Lakes Clive Iowa
United States Billings Clinic-Cody Cody Wyoming
United States Kootenai Medical Center Coeur d'Alene Idaho
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado
United States Columbus Oncology and Hematology Associates Inc Columbus Ohio
United States Doctors Hospital Columbus Ohio
United States Grant Medical Center Columbus Ohio
United States Mount Carmel East Hospital Columbus Ohio
United States Mount Carmel Health Center West Columbus Ohio
United States Ohio State University Comprehensive Cancer Center Columbus Ohio
United States Riverside Methodist Hospital Columbus Ohio
United States The Mark H Zangmeister Center Columbus Ohio
United States John Muir Medical Center-Concord Campus Concord California
United States Mercy Hospital Coon Rapids Minnesota
United States Commonwealth Cancer Center-Corbin Corbin Kentucky
United States Alegent Health Mercy Hospital Council Bluffs Iowa
United States Greater Regional Medical Center Creston Iowa
United States Geisinger Medical Center Danville Pennsylvania
United States Delaware Health Center-Grady Cancer Center Delaware Ohio
United States Delaware Radiation Oncology Delaware Ohio
United States Grady Memorial Hospital Delaware Ohio
United States Colorado Blood Cancer Institute Denver Colorado
United States Denver Health Medical Center Denver Colorado
United States National Jewish Health-Main Campus Denver Colorado
United States Porter Adventist Hospital Denver Colorado
United States Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado
United States Rocky Mountain Cancer Centers-Midtown Denver Colorado
United States Rocky Mountain Cancer Centers-Rose Denver Colorado
United States Rose Medical Center Denver Colorado
United States SCL Health Saint Joseph Hospital Denver Colorado
United States The Women's Imaging Center Denver Colorado
United States Medical Oncology and Hematology Associates-Laurel Des Moines Iowa
United States Mercy Medical Center - Des Moines Des Moines Iowa
United States Mercy Medical Center Durango Colorado
United States Southwest Oncology PC Durango Colorado
United States Duke University Medical Center Durham North Carolina
United States Prisma Health Cancer Institute - Easley Easley South Carolina
United States Fairview Southdale Hospital Edina Minnesota
United States Mountain Blue Cancer Care Center - Swedish Englewood Colorado
United States Swedish Medical Center Englewood Colorado
United States Saint Elizabeth Hospital Enumclaw Washington
United States Saint Francis Hospital Federal Way Washington
United States Parkview Hospital Randallia Fort Wayne Indiana
United States Vanderbilt-Ingram Cancer Center Cool Springs Franklin Tennessee
United States Unity Hospital Fridley Minnesota
United States Mountain Blue Cancer Care Center Golden Colorado
United States National Jewish Health-Western Hematology Oncology Golden Colorado
United States CHI Health Saint Francis Grand Island Nebraska
United States Benefis Healthcare- Sletten Cancer Institute Great Falls Montana
United States Great Falls Clinic Great Falls Montana
United States North Colorado Medical Center Greeley Colorado
United States UPMC Cancer Centers - Arnold Palmer Pavilion Greensburg Pennsylvania
United States Prisma Health Cancer Institute - Butternut Greenville South Carolina
United States Prisma Health Cancer Institute - Eastside Greenville South Carolina
United States Prisma Health Cancer Institute - Faris Greenville South Carolina
United States Prisma Health Greenville Memorial Hospital Greenville South Carolina
United States Prisma Health Cancer Institute - Greer Greer South Carolina
United States Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania
United States Saint Peter's Community Hospital Helena Montana
United States Pulmonary Medicine Center of Chattanooga-Hixson Hixson Tennessee
United States CHI Saint Vincent Cancer Center Hot Springs Hot Springs Arkansas
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States UPMC-Johnstown/John P. Murtha Regional Cancer Center Johnstown Pennsylvania
United States Freeman Health System Joplin Missouri
United States Mercy Hospital Joplin Joplin Missouri
United States Kalispell Regional Medical Center Kalispell Montana
United States University of Kansas Cancer Center Kansas City Kansas
United States CHI Health Good Samaritan Kearney Nebraska
United States Heartland Hematology and Oncology Kearney Nebraska
United States Northwestern Medicine Lake Forest Hospital Lake Forest Illinois
United States Rocky Mountain Cancer Centers-Lakewood Lakewood Colorado
United States Saint Anthony Hospital Lakewood Colorado
United States Saint Clare Hospital Lakewood Washington
United States Fairfield Medical Center Lancaster Ohio
United States Women's Cancer Center of Nevada Las Vegas Nevada
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States Beebe Medical Center Lewes Delaware
United States Geisinger Medical Oncology-Lewisburg Lewisburg Pennsylvania
United States Lewistown Hospital Lewistown Pennsylvania
United States Saint Joseph Hospital East Lexington Kentucky
United States Saint Joseph Radiation Oncology Resource Center Lexington Kentucky
United States Saint Elizabeth Regional Medical Center Lincoln Nebraska
United States Littleton Adventist Hospital Littleton Colorado
United States Rocky Mountain Cancer Centers-Littleton Littleton Colorado
United States Saint Joseph London London Kentucky
United States Rocky Mountain Cancer Centers-Sky Ridge Lone Tree Colorado
United States Longmont United Hospital Longmont Colorado
United States Rocky Mountain Cancer Centers-Longmont Longmont Colorado
United States Jewish Hospital Louisville Kentucky
United States Jewish Hospital Medical Center Northeast Louisville Kentucky
United States Saints Mary and Elizabeth Hospital Louisville Kentucky
United States McKee Medical Center Loveland Colorado
United States OhioHealth Mansfield Hospital Mansfield Ohio
United States Fairview Clinics and Surgery Center Maple Grove Maple Grove Minnesota
United States Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota
United States Saint John's Hospital - Healtheast Maplewood Minnesota
United States Marietta Memorial Hospital Marietta Ohio
United States OhioHealth Marion General Hospital Marion Ohio
United States UPMC Cancer Center at UPMC McKeesport McKeesport Pennsylvania
United States Abbott-Northwestern Hospital Minneapolis Minnesota
United States Health Partners Inc Minneapolis Minnesota
United States Hennepin County Medical Center Minneapolis Minnesota
United States Community Medical Hospital Missoula Montana
United States UPMC-Coraopolis/Heritage Valley Radiation Oncology Moon Pennsylvania
United States Good Samaritan Regional Health Center Mount Vernon Illinois
United States Knox Community Hospital Mount Vernon Ohio
United States Vanderbilt Breast Center at One Hundred Oaks Nashville Tennessee
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States UC Comprehensive Cancer Center at Silver Cross New Lenox Illinois
United States Louisiana State University Health Science Center New Orleans Louisiana
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Cancer Center of Western Wisconsin New Richmond Wisconsin
United States New Ulm Medical Center New Ulm Minnesota
United States Christiana Care Health System-Christiana Hospital Newark Delaware
United States Delaware Clinical and Laboratory Physicians PA Newark Delaware
United States Helen F Graham Cancer Center Newark Delaware
United States Licking Memorial Hospital Newark Ohio
United States Medical Oncology Hematology Consultants PA Newark Delaware
United States Newark Radiation Oncology Newark Ohio
United States Mercy Hospital Oklahoma City Oklahoma City Oklahoma
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Alegent Health Bergan Mercy Medical Center Omaha Nebraska
United States Alegent Health Immanuel Medical Center Omaha Nebraska
United States Alegent Health Lakeside Hospital Omaha Nebraska
United States Creighton University Medical Center Omaha Nebraska
United States Hematology and Oncology Consultants PC Omaha Nebraska
United States Memorial GYN Plus Ooltewah Tennessee
United States University of Chicago Medicine-Orland Park Orland Park Illinois
United States Midlands Community Hospital Papillion Nebraska
United States Parker Adventist Hospital Parker Colorado
United States Rocky Mountain Cancer Centers-Parker Parker Colorado
United States Sacred Heart Hospital Pensacola Florida
United States University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania
United States UPMC-Magee Womens Hospital Pittsburgh Pennsylvania
United States UPMC-Passavant Hospital Pittsburgh Pennsylvania
United States UPMC-Presbyterian Hospital Pittsburgh Pennsylvania
United States UPMC-Saint Clair Hospital Cancer Center Pittsburgh Pennsylvania
United States UPMC-Saint Margaret Pittsburgh Pennsylvania
United States UPMC-Shadyside Hospital Pittsburgh Pennsylvania
United States Southern Ohio Medical Center Portsmouth Ohio
United States Kootenai Cancer Center Post Falls Idaho
United States Geisinger Cancer Services-Pottsville Pottsville Pennsylvania
United States Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington
United States Women and Infants Hospital Providence Rhode Island
United States Rocky Mountain Cancer Centers - Pueblo Pueblo Colorado
United States Saint Mary Corwin Medical Center Pueblo Colorado
United States Beebe Health Campus Rehoboth Beach Delaware
United States North Memorial Medical Health Center Robbinsdale Minnesota
United States University of Rochester Rochester New York
United States Delbert Day Cancer Institute at PCRMC Rolla Missouri
United States Mercy Clinic-Rolla-Cancer and Hematology Rolla Missouri
United States Heartland Regional Medical Center Saint Joseph Missouri
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri
United States Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota
United States Regions Hospital Saint Paul Minnesota
United States United Hospital Saint Paul Minnesota
United States Kootenai Cancer Clinic Sandpoint Idaho
United States Community Medical Center Scranton Pennsylvania
United States TidalHealth Nanticoke / Allen Cancer Center Seaford Delaware
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States Seattle Cancer Care Alliance Seattle Washington
United States University of Washington Medical Center Seattle Washington
United States Geisinger Medical Oncology-Selinsgrove Selinsgrove Pennsylvania
United States Prisma Health Cancer Institute - Seneca Seneca South Carolina
United States UPMC Cancer Center at UPMC Northwest Seneca Pennsylvania
United States Saint Francis Regional Medical Center Shakopee Minnesota
United States Jewish Hospital Medical Center South Shepherdsville Kentucky
United States Welch Cancer Center Sheridan Wyoming
United States Willis-Knighton Medical and Cancer Center Shreveport Louisiana
United States Prisma Health Cancer Institute - Spartanburg Spartanburg South Carolina
United States CoxHealth South Hospital Springfield Missouri
United States Mercy Hospital Springfield Springfield Missouri
United States Geisinger Medical Group State College Pennsylvania
United States Lakeview Hospital Stillwater Minnesota
United States Franciscan Research Center-Northwest Medical Plaza Tacoma Washington
United States Northwest Medical Specialties PLLC Tacoma Washington
United States National Jewish Health-Northern Hematology Oncology Thornton Colorado
United States Rocky Mountain Cancer Centers-Thornton Thornton Colorado
United States Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma
United States UPMC Uniontown Hospital Radiation Oncology Uniontown Pennsylvania
United States Ridgeview Medical Center Waconia Minnesota
United States John Muir Medical Center-Walnut Creek Walnut Creek California
United States Mercy Hospital Washington Washington Missouri
United States UPMC Washington Hospital Radiation Oncology Washington Pennsylvania
United States Mercy Medical Center-West Lakes West Des Moines Iowa
United States Saint Ann's Hospital Westerville Ohio
United States University of Kansas Hospital-Westwood Cancer Center Westwood Kansas
United States SCL Health Lutheran Medical Center Wheat Ridge Colorado
United States Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania
United States Rice Memorial Hospital Willmar Minnesota
United States Christiana Care Health System-Wilmington Hospital Wilmington Delaware
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota
United States Fairview Lakes Medical Center Wyoming Minnesota
United States Genesis Healthcare System Cancer Care Center Zanesville Ohio

Sponsors (2)

Lead Sponsor Collaborator
National Cancer Institute (NCI) NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Mean Post-treatment Tumor Estrogen Receptor Score Up to 3 years
Other Co-expression of PR, Ki67, and p21 Will be compared between the arms. Up to 3 years
Primary 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. Specimens were collected at hysterectomy on day 21-24 and analyzed in batch.
Secondary 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). Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.
Secondary 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. Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.
Secondary 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. Up to 45 days after surgery
See also
  Status Clinical Trial Phase
Active, not recruiting NCT02397083 - Levonorgestrel-Releasing Intrauterine System With or Without Everolimus in Treating Patients With Atypical Hyperplasia or Stage IA Grade 1 Endometrial Cancer Phase 2
Recruiting NCT04604613 - Prediction of Recurrence Among Low Risk Endometrial Cancer Patients
Active, not recruiting NCT03300557 - Exemestane in Treating Patients With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer Phase 2
Recruiting NCT04092270 - A Study Combining the Peposertib (M3814) Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer Phase 1
Recruiting NCT05538897 - Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers Phase 1/Phase 2
Recruiting NCT06213571 - Remote Home-Based Exercise Program for Strength Training in Endometrial Cancer Survivors in Rural Areas N/A