Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer; Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Medroxyprogesterone; Procedure: Therapeutic Conventional Surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Medroxyprogesterone; Given IM; Other Names: Curretab; Procedure: Therapeutic Conventional Surgery; Undergo surgical hysterectomy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Richard Zaino, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): September 1, 2010

Study Registration Dates

• First Submitted: July 8, 2003
• First Submitted That Met QC Criteria: July 8, 2003
• First Posted (ESTIMATE): July 9, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): April 11, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Neoplasms, Complex and Mixed; Ovarian Neoplasms; Endometrial Neoplasms; Carcinoma; Adenocarcinoma; Carcinoma, Endometrioid; Carcinoma, Adenosquamous; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: GOG-0211 (OTHER: CTEP); U10CA027469 (U.S. NIH Grant/Contract); NCI-2012-02539 (REGISTRY: CTRP (Clinical Trial Reporting Program)); CDR0000306440