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

  • Interventional
  • Not Recruiting
  • NCT03018249
Eligibility Details Visit Clinicaltrials.gov

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

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.

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.

Gender
Female

Age Group
18 Years and up

Accepting 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)

At a Glance

National Government IDNCT03018249

IRB#CIRB17-1374

Lead SponsorNational Cancer Institute (NCI)

Lead PhysicianRebecca A Brooks

Collaborator(s)N/A

EligibilityFemale
18 Years and up
Not Recruiting