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

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ClinicalTrials.gov Identifier: NCT03018249
Recruitment Status : Active, not recruiting
First Posted : January 12, 2017
Last Update Posted : September 6, 2019
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE January 11, 2017
First Posted Date  ICMJE January 12, 2017
Last Update Posted Date September 6, 2019
Actual Study Start Date  ICMJE August 25, 2017
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2018)
Mean post-treatment tumor progesterone receptor score [ Time Frame: Up to 3 years ]
The percent cells staining positive multiplied by the staining intensity will be compared between treatment arms to evaluate the association of the addition of entinostat treatment on tumor progesterone receptor expression. A treatment difference in the distribution of post-treatment progesterone receptor scores will be tested using a Mann-Whitney test. An analysis of covariance model could be used to test the treatment difference while adjusting for pre-treatment progesterone receptor scores or testing the mean post-treatment - pre-treatment differences could be compared between arms with a T test.
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
Mean post-treatment tumor progesterone receptor score [ Time Frame: Up to 3 years ]
The percent cells staining positive multiplied by the staining intensity will be compared between treatment arms to evaluate the association of the addition of entinostat treatment on tumor progesterone receptor expression. A treatment difference in the distribution of post-treatment progesterone receptor scores will be tested using a Mann-Whitney test. An analysis of covariance model could be used to test the treatment difference while adjusting for pre-treatment progesterone receptor scores or testing the mean post-treatment - pre-treatment differences could be compared between arms with a T
Change History Complete list of historical versions of study NCT03018249 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2018)
  • Proportion of patients with a histologic tumor response (complete or partial) [ Time Frame: Up to 3 years ]
    Will compare the difference in the proportion of patients with a histologic tumor response (complete or partial) between treatment arms.
  • Mean post-treatment tumor Ki67 score [ Time Frame: Up to 3 years ]
    The percent cells staining positive multiplied by the staining intensity will be compared between treatment arms. A treatment difference in the distribution of post-treatment tumor Ki67 scores will be tested using a Mann-Whitney test. An analysis of covariance model could be used to test the treatment difference while adjusting for pre-treatment tumor Ki67 scores or testing the mean post-treatment - pre-treatment differences could be compared between arms with a T test. A confidence interval around the estimate of the treatment difference in the proportion with a histologic response will be constructed. Correlation between Ki67 and histologic response will be evaluated by treatment team.
  • Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 45 days after surgery ]
    The frequency and maximum severity of acute drug emergent and post-surgical adverse events will be tabulated by treatment arm.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
  • Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 45 days after surgery ]
    The frequency and severity of all toxicities will be tabulated.
  • Mean post-treatment tumor estrogen receptor score [ Time Frame: Up to 3 years ]
    The percent cells staining positive multiplied by the staining intensity will be compared between treatment arms. A treatment difference in the distribution of post-treatment estrogen receptor scores will be tested using a Mann-Whitney test. An analysis of covariance model could be used to test the treatment difference while adjusting for pre-treatment estrogen receptor scores or testing the mean post-treatment - pre-treatment differences could be compared between arms with a T test. A confidence interval around the estimate of the treatment difference in the proportion with a histologic respo
  • Mean post-treatment tumor Ki67 score [ Time Frame: Up to 3 years ]
    The percent cells staining positive multiplied by the staining intensity will be compared between treatment arms. A treatment difference in the distribution of post-treatment tumor Ki67 scores will be tested using a Mann-Whitney test. An analysis of covariance model could be used to test the treatment difference while adjusting for pre-treatment tumor Ki67 scores or testing the mean post-treatment - pre-treatment differences could be compared between arms with a T test. A confidence interval around the estimate of the treatment difference in the proportion with a histologic response will be co
  • Mean post-treatment tumor p21 receptor score [ Time Frame: Up to 3 years ]
    The percent cells staining positive multiplied by the staining intensity will be compared between treatment arms. A treatment difference in the distribution of post-treatment tumor p21 scores will be tested using a Mann-Whitney test. An analysis of covariance model could be used to test the treatment difference while adjusting for pre-treatment tumor p21 scores or testing the mean post-treatment - pre-treatment differences could be compared between arms with a T test. A confidence interval around the estimate of the treatment difference in the proportion with a histologic response will be cons
  • Proportion of patients with a histologic tumor response (complete or partial) [ Time Frame: Up to 3 years ]
    Will compare the difference in the proportion of patients with a histologic tumor response (complete or partial) between treatment arms.
Current Other Pre-specified Outcome Measures
 (submitted: December 13, 2018)
  • Mean post-treatment tumor estrogen receptor score [ Time Frame: Up to 3 years ]
  • Co-expression of PR, Ki67, and p21 [ Time Frame: Up to 3 years ]
    Will be compared between the treatment arms.
Original Other Pre-specified Outcome Measures
 (submitted: January 11, 2017)
Co-expression of PR, Ki67, and p21 [ Time Frame: Up to 3 years ]
Will be compared between the treatment arms.
 
Descriptive Information
Brief Title  ICMJE Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer
Official Title  ICMJE 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
Brief Summary This randomized phase II trial studies how well medroxyprogesterone acetate with or without entinostat before surgery works in treating patients with endometrioid endometrial cancer. 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. Given medroxyprogesterone acetate with or without entinostat may work better in treating patients with endometrioid endometrial cancer.
Detailed 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: Patients are randomized into 1 of 2 arms.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
  • FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma
  • FIGO Grade 3 Endometrial Endometrioid Adenocarcinoma
  • Uterine Corpus Adenosarcoma
Intervention  ICMJE
  • Drug: Entinostat
    Given PO
    Other Names:
    • HDAC inhibitor SNDX-275
    • MS 27-275
    • MS-275
    • SNDX-275
  • Procedure: Hysterectomy
    Undergo hysterectomy
  • 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
Study Arms  ICMJE
  • Active Comparator: Arm I (medroxyprogesterone acetate, hysterectomy)
    Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.
    Interventions:
    • Procedure: Hysterectomy
    • Other: Laboratory Biomarker Analysis
    • Drug: Medroxyprogesterone Acetate
  • 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.
    Interventions:
    • Drug: Entinostat
    • Procedure: Hysterectomy
    • Other: Laboratory Biomarker Analysis
    • Drug: Medroxyprogesterone Acetate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03018249
Other Study ID Numbers  ICMJE NCI-2017-00058
NCI-2017-00058 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY011
NRG-GY011 ( Other Identifier: NRG Oncology )
NRG-GY011 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE NRG Oncology
Investigators  ICMJE
Principal Investigator: Linda R Duska NRG Oncology
PRS Account National Cancer Institute (NCI)
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP