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
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 234
- 主要终点
- Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Arm I (medroxyprogesterone acetate, hysterectomy)
Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.
干预措施: Hysterectomy (Procedure)
Arm I (medroxyprogesterone acetate, hysterectomy)
Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (medroxyprogesterone acetate, hysterectomy)
Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.
干预措施: Medroxyprogesterone Acetate (Drug)
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.
干预措施: Entinostat (Drug)
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.
干预措施: Hysterectomy (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Medroxyprogesterone Acetate (Drug)
结局指标
主要结局
Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)
时间窗: Specimens were collected at hysterectomy on day 21-24 and analyzed in batch.
The H-score is defined as the percent cells staining positive (0-100) multiplied by the staining intensity (0, 1, 2 or 3) measured in the tumor by immunohistochemistry and averaged over 3 reviewers. This score can range from 0 to 300. In general, PRs are expected to decrease in response to medroxyprogesterone acetate. It was hypothesized that entinostat would mitigate the decrease in PR relative to the medroxyprogesterone acetate only arm post treatment. Higher PR H-scores post treatment in the arm with entinostat relative to the medroxyprogesterone alone arm would be consistent with this hypothesis. Arm II was thought to result in higher scores which was expected to have a more favorable outcome when treated with MPA therapy.
次要结局
- Percent of Participants With a Ki67 Response(Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.)
- Percentage of Participants With a Histologic Response(Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.)
- The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE)(Up to 45 days after surgery)