Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

Study Overview
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Brief Summary
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This phase II trial is studying how well medroxyprogesterone works in treating patients with endometrioid adenocarcinoma (cancer) of the uterine corpus (the body of the uterus, not including the cervix). Hormone therapy using medroxyprogesterone may be effective in treating endometrioid cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Compare the efficacy of medroxyprogesterone, in terms of induction of histologic response, in patients with progesterone receptor-positive vs progesterone receptor-negative endometrioid adenocarcinoma of the uterine corpus. II. Determine the early and late changes in gene expression at 72 hours and 21 days in patients treated with this drug. III. Examine the mechanisms surrounding the dynamic changes in endometrial tumor cells by determining possible correlations among histologic response, steroid receptor status, immunohistochemical measures of growth and apoptosis, and gene expression profiles in patients treated with this drug. OUTLINE: This is a pilot, multicenter study. Patients receive medroxyprogesterone intramuscularly once approximately 3 weeks before surgical hysterectomy. A subset of 15 patients has tissue collected by pipelle biopsy or curettage at baseline, 72 hours after medroxyprogesterone therapy, and during surgery for gene expression arrays. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Official Title
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A Phase II Pilot Investigation Of The Relationship Of Short Term Depo-Provera (Medroxyprogesterone Acetate) Exposure To The Morphologic , Biochemical, And Molecular Changes In Primary Endometroid Adenocarcinoma of the Uterine Corpus

Conditions
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Endometrial Adenocarcinoma, Endometrial Adenosquamous Carcinoma, Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation, Recurrent Uterine Corpus Carcinoma, Stage I Uterine Corpus Cancer, Stage II Uterine Corpus Cancer, Stage III Uterine Corpus Cancer, Stage IV Uterine Corpus Cancer

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Drug: Medroxyprogesterone
* Procedure: Therapeutic Conventional Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary endometrioid adenocarcinoma of the uterine corpus All histologic grades and stages eligible Diagnosis by endometrial curettage or biopsy within the past 8 weeks Must have the initial tissue block or 16 unstained sections of 5 micron thickness available Performance status - GOG 0-3 No history of thrombophlebitis or thromboembolic disorders No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No prior therapeutic progesterone or anti-estrogen therapy within 3 months before diagnosis No concurrent aminoglutethimide No prior cancer treatment that would preclude study therapy No concurrent bosentan No concurrent rifampin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (medroxyprogesterone)<br>Patients receive medroxyprogesterone intramuscularly once approximately 3 weeks before surgical hysterectomy. A subset of 15 patients has tissue collected by pipelle biopsy or curettage at baseline, 72 hours after medroxyprogesterone therapy, and during surgery for gene expression arrays. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Medroxyprogesterone<br>* Given IM<br>* Other names: Curretab;Procedure: Therapeutic Conventional Surgery<br>* Undergo surgical hysterectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologic Response in Endometrial Adenocarcinomas of the Uterine Corpus That Are Progesterone Receptor Positive Compared With Those That Are Progesterone Receptor Negative | To determine the presence of a histologic response, the slide from the initial sample was compared to the slide from the matching hysterectomy specimen. A complete histologic response was defined as the absence of identifiable adenocarcinoma in the hysterectomy specimen section. A partial histologic response was subjectively defined in advance of the study based on criteria slightly modified from Wheeler et al. (Am J Surg Pathol 2007;31:988-98) as the presence of a complex proliferation of glands that retain the architectural characteristics of adenocarcinoma, but with features of secretion, decreased nuclear stratification, or the presence of eosinophilic, squamous or mucinous metaplasia, when this was absent in the initial sample. A complete or partial histologic response was considered a histologic response in the analysis of data. PR Positivity is based on aggregate score >0.2 (vs. <=0.2). Aggregate score based on product of staining intensity and area. | During the hysterectomy, which is 21-24 days after administration of depo-provera | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Pre- to Post-treatment in Estrogren Receptor (ER) Expression | Expression is based on an aggregate score based on immunohistochemistry. Staining intensity was scored 1, 2, or 3; and staining area was scored as a percentage (0-100%). The aggregate score is the product of staining intensity and area and ranges from 0 to 3. | During the hysterectomy, which is 21-24 days after administration of depo-provera | 
| Change From Pre- to Post-treatment in Progestrogren Receptor (PR) Expression | Expression is based on an aggregate score based on immunohistochemistry. Staining intensity was scored 1, 2, or 3; and staining area was scored as a percentage (0-100%). The aggregate score is the product of staining intensity and area and ranges from 0 to 3. | During the hysterectomy , which is 21-24 days after administration of depo-provera |