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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Randomized Surgical Window Pilot Investigation of the Relationship of Short Term Depo-Provera (Medroxyprogesterone Acetate) (NSC #26386) Compared to Depo-Provera Plus Entinostat (NSC #706995) on the

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 Summary:

PRIMARY OBJECTIVES:

I. To determine whether the addition of the histone deacetylase inhibitor, entinostat, in combination with medroxyprogesterone acetate (Depo-Provera) in the pre-operative setting results in up-regulation of activated progesterone receptors (PR) compared to Depo-Provera 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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 11, 2017
Date Started: August 25, 2017
Date Completion: December 31, 2020
Last Updated: April 23, 2017
Last Verified: April 2017