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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 : August 15, 2019
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma FIGO Grade 3 Endometrial Endometrioid Adenocarcinoma Uterine Corpus Adenosarcoma Drug: Entinostat Procedure: Hysterectomy Other: Laboratory Biomarker Analysis Drug: Medroxyprogesterone Acetate Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : August 25, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hysterectomy

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: 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: 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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Other Outcome Measures:
  1. Mean post-treatment tumor estrogen receptor score [ Time Frame: Up to 3 years ]
  2. Co-expression of PR, Ki67, and p21 [ Time Frame: Up to 3 years ]
    Will be compared between the treatment arms.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03018249


  Show 234 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
NRG Oncology
Investigators
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Principal Investigator: Linda R Duska NRG Oncology

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03018249     History of Changes
Other Study ID Numbers: 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 )
First Posted: January 12, 2017    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Entinostat
Adenocarcinoma
Carcinoma, Endometrioid
Adenosarcoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Ovarian Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Connective and Soft Tissue
Medroxyprogesterone Acetate
Medroxyprogesterone
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs