Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00064025
First received: July 8, 2003
Last updated: March 17, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
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
Other: Laboratory Biomarker Analysis
Drug: Medroxyprogesterone
Procedure: Therapeutic Conventional Surgery
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Histologic Response in Endometrial Adenocarcinomas of the Uterine Corpus That Are Progesterone Receptor Positive Compared With Those That Are Progesterone Receptor Negative [ Time Frame: During the hysterectomy, which is 21-24 days after administration of depo-provera ] [ Designated as safety issue: No ]

    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:
  • Change From Pre- to Post-treatment in Estrogren Receptor (ER) Expression [ Time Frame: During the hysterectomy, which is 21-24 days after administration of depo-provera ] [ Designated as safety issue: No ]
    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 [ Time Frame: During the hysterectomy , which is 21-24 days after administration of depo-provera ] [ Designated as safety issue: No ]
    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.


Enrollment: 75
Study Start Date: April 2004
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Curretab
Procedure: Therapeutic Conventional Surgery
Undergo surgical hysterectomy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064025

Locations
United States, Pennsylvania
Gynecologic Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Gynecologic Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Richard Zaino Gynecologic Oncology Group
  More Information

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00064025     History of Changes
Other Study ID Numbers: GOG-0211  NCI-2012-02539  CDR0000306440  GOG-0211  GOG-0211  U10CA027469 
Study First Received: July 8, 2003
Results First Received: January 31, 2014
Last Updated: March 17, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Adenosquamous
Carcinoma, Endometrioid
Uterine Neoplasms
Adnexal Diseases
Endocrine System Diseases
Endometrial Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Glandular and Epithelial
Ovarian Diseases
Ovarian Neoplasms
Urogenital Neoplasms
Uterine Diseases
Medroxyprogesterone
Medroxyprogesterone Acetate
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2016