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

National Cancer Institute (NCI)

Status and phase: Completed; Early Phase 1

Conditions: FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 3 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma

Treatments: Drug: Medroxyprogesterone Acetate; Procedure: Hysterectomy; Other: Laboratory Biomarker Analysis; Drug: Entinostat

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03018249

U10CA180868 (U.S. NIH Grant/Contract)

NCI-2017-00058 (Registry Identifier)

NRG-GY011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Arm I (medroxyprogesterone acetate, hysterectomy)

Active Comparator group

Description:

Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.

Treatment:

Other: Laboratory Biomarker Analysis

Procedure: Hysterectomy

Drug: Medroxyprogesterone Acetate

Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)

Experimental group

Description:

Patients receive medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.

Treatment:

Drug: Entinostat

Other: Laboratory Biomarker Analysis

Procedure: Hysterectomy

Drug: Medroxyprogesterone Acetate