Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

Phase 2

Completed

Conditions: 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

Interventions: Other: Laboratory Biomarker Analysis
Drug: Medroxyprogesterone
Procedure: Therapeutic Conventional Surgery

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Treatment (medroxyprogesterone)	Laboratory Biomarker Analysis	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.
Treatment (medroxyprogesterone)	Medroxyprogesterone	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.
Treatment (medroxyprogesterone)	Therapeutic Conventional Surgery	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.

Primary Outcome Measures

Name	Time	Method
Histologic Response in Endometrial Adenocarcinomas of the Uterine Corpus That Are Progesterone Receptor Positive Compared With Those That Are Progesterone Receptor Negative	During the hysterectomy, which is 21-24 days after administration of depo-provera	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.

Secondary Outcome Measures

Name	Time	Method
Change From Pre- to Post-treatment in Estrogren Receptor (ER) Expression	During the hysterectomy, which is 21-24 days after administration of depo-provera	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.
Change From Pre- to Post-treatment in Progestrogren Receptor (PR) Expression	During the hysterectomy , which is 21-24 days after administration of depo-provera	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.