Clinical Trial: The Effect of Neoadjuvant DMPA on Glandular Cellularity in Women Awaiting Hysterectomy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: The Effect of Neoadjuvant Depot Medroxyprogesterone Acetate on Glandular Cellularity in Women With Complex Atypical Hyperplasia or Grade 1-2 Endometrial Adenocarcinoma Awaiting Hysterectomy

Brief Summary:

Objective: To compare pre- and post-treatment glandular cellularity in women with complex atypical hyperplasia or grade 1-2 endometrial adenocarcinoma who are treated with intramuscular depot medroxyprogesterone acetate (DMPA) versus placebo injection prior to hysterectomy. The secondary objective is to compare various other outcomes including molecular, histologic, pathologic and clinical endpoints in women treated with DMPA versus placebo prior to hysterectomy.

Hypothesis: Patients treated with DMPA will have significantly decreased glandular cellularity post-treatment when compared to patients treated with placebo injection. Patients treated with DMPA will exhibit previously described changes in molecular tumor marker expression patterns and other characteristic histologic changes. Patients treated with DMPA will report less bothersome vaginal bleeding prior to surgery when compared to patients treated with placebo injection.

Study Design: Double blinded randomized controlled trial

Population: Women being treated at the Women and Infants Program in Women's Oncology who have a biopsy-proven diagnosis of complex atypical hyperplasia or grade 1-2 endometrial adenocarcinoma with disease clinically confined to the uterus, with a plan to undergo hysterectomy.

Study Period: February 2015 to June 2016


Detailed Summary:

BACKGROUND/INTRODUCTION:

Recently, multiple modalities of progesterone analogues have been investigated and successfully used to treat complex atypical hyperplasia (CAH) and stage 1A, grade 1 endometrial adenocarcinoma. This body of research focuses on pre-menopausal women with the primary goal of preserving fertility by delaying or avoiding surgical therapy. Across multiple case series, the average time to complete response (CR: typically defined as the absence of hyperplasia, atypia or neoplasia on a follow-up biopsy specimen) is 5-9 months with 60-70% overall complete response rate and approximately 50% durable complete response rate (defined as complete histologic response with no relapse of disease over the period of time studied). There have been no published randomized controlled trials to evaluate which modality of progesterone therapy is the most efficacious, and there is no consistent retrospective data to suggest superiority of any given progesterone analogue or method of administration.

Multiple pathologic predictors of complete response to progesterone therapy have been identified. In a recent study, Gunderson found that an interval decrease in glandular cellularity on endometrial biopsy after treatment with progesterone therapy was an independent predictor of future complete response. While both decreased mitotic index and decreased glandular cellularity were significant findings in this study, only decreased glandular cellularity was independently predictive of future complete response on multivariate analysis.

Despite this growing body of evidence supporting the safety and feasibility of progesterone analogues as medical management for CAH and early-stage endometrial adenocarcinoma, little is known about its potential role as neoadjuvant chemotherapy. A rece
Sponsor: Women and Infants Hospital of Rhode Island

Current Primary Outcome: Change in glandular cellularity [ Time Frame: 2-3 weeks after hysterectomy ]

Histologic analysis of glandular cellularity in hysterectomy specimens as compared to pre-hysterectomy endometrial tissue


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in mitotic index [ Time Frame: 2-3 weeks after hysterectomy ]
    Histologic analysis of mitotic index in hysterectomy specimens as compared to pre-hysterectomy endometrial tissue
  • Histologic grade [ Time Frame: 2-3 weeks after hysterectomy ]
    Histologic analysis of tumor grade in hysterectomy specimens
  • Depth of invasion [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of depth of invasion in hysterectomy specimens
  • Tumor size [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of tumor size in hysterectomy specimens
  • Lymph node involvement [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of lymph node involvement in surgical specimens
  • Lymphovascular invasion [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of lymphovascular invasion in surgical specimens
  • Estrogen Receptor immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Estrogen Receptor status in tumor specimen
  • Progesterone Receptor immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Progesterone Receptor status in tumor specimen
  • Progesterone Receptor Beta immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Progesterone Receptor Beta status in tumor specimen
  • B-Cell-Lymphoma-2 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of BCL2 status in tumor specimen
  • Ki-67 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Ki-67 status in tumor specimen
  • Caspase-3 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Casp3 status in tumor specimen
  • Phospho-Histone-H3 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of PHH3 status in tumor specimen
  • Functional Assessment of Cancer Therapy - Endometrial cancer version [ Time Frame: 1-2 hours prior to hysterectomy ]
    Quality of life survey FACT-En, administered 1-2 hours prior to surgery
  • Hemoglobin level [ Time Frame: 12-24 hours after hysterectomy ]
    Hemoglobin level drawn 12-24 hours after hysterectomy to evaluate if DMPA improves blood count via diminished bleeding
  • Final cancer stage [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic determination of patient's definitive stage of endometrial cancer per FIGO guidelines


Original Secondary Outcome:

  • Change in mitotic index [ Time Frame: 2-3 weeks after hysterectomy ]
    Histologic analysis of mitotic index in hysterectomy specimens as compared to pre-hysterectomy endometrial tissue
  • Histologic grade [ Time Frame: 2-3 weeks after hysterectomy ]
    Histologic analysis of tumor grade in hysterectomy specimens
  • Depth of invasion [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of depth of invasion in hysterectomy specimens
  • Tumor size [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of tumor size in hysterectomy specimens
  • Lymph node involvement [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of lymph node involvement in surgical specimens
  • Lymphovascular invasion [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic analysis of lymphovascular invasion in surgical specimens
  • Estrogen Receptor immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Estrogen Receptor status in tumor specimen
  • Progesterone Receptor immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Progesterone Receptor status in tumor specimen
  • Progesterone Receptor Beta immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Progesterone Receptor Beta status in tumor specimen
  • B-Cell-Lymphoma-2 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of BCL2 status in tumor specimen
  • Ki-67 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Ki-67 status in tumor specimen
  • Caspase-3 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of Casp3 status in tumor specimen
  • Phospho-Histone-H3 immunohistochemistry analysis [ Time Frame: 2-3 weeks after hysterectomy ]
    Immunohistochemical analysis of PHH3 status in tumor specimen
  • Functional Assessment of Cancer Therapy - Endometrial cancer version [ Time Frame: 1-2 hours prior to hysterectomy ]
    Quality of life survey FACT-En, administered 1-2 hours prior to surgery
  • Hemoglobin level [ Time Frame: 1-2 hours prior to hysterectomy ]
    Hemoglobin level drawn 1-2 hours prior to hysterectomy to evaluate if DMPA improves blood count via diminished bleeding
  • Final cancer stage [ Time Frame: 2-3 weeks after hysterectomy ]
    Pathologic determination of patient's definitive stage of endometrial cancer per FIGO guidelines


Information By: Women and Infants Hospital of Rhode Island

Dates:
Date Received: December 22, 2014
Date Started: February 2015
Date Completion: June 2018
Last Updated: September 17, 2016
Last Verified: September 2016