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
Conditions
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
Given IM
PROCEDURETherapeutic Conventional Surgery
Undergo surgical hysterectomy
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
The study was activated on 4/12/2004 and closed to accrual on 9/2/2008.
Participants by arm
| Arm | Count |
|---|---|
| Depo-Provera Depo-Provera (Medroxyprogesterone Acetate) 400 mg IM, Given Once, 21-24 Days Prior to Hysterectomy | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 4 |
| Overall Study | Inevaluable | 3 |
Baseline characteristics
| Characteristic | Depo-Provera |
|---|---|
| Age, Customized 30-39 years | 1 participants |
| Age, Customized 40-49 years | 3 participants |
| Age, Customized 50-59 years | 28 participants |
| Age, Customized 60-69 years | 30 participants |
| Age, Customized 70-79 years | 3 participants |
| Age, Customized 80-89 years | 3 participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 68 |
| serious Total, serious adverse events | 0 / 68 |
Outcome results
Primary
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.
Time frame: During the hysterectomy, which is 21-24 days after administration of depo-provera
Population: Eligible and Evaluable Patients (patients who had both an intake biopsy and hysterectomy and had histologic response data)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PR Negative (<=0.2) | Histologic Response in Endometrial Adenocarcinomas of the Uterine Corpus That Are Progesterone Receptor Positive Compared With Those That Are Progesterone Receptor Negative | 62.5 percentage of participants |
| PR Positive (>0.2) | Histologic Response in Endometrial Adenocarcinomas of the Uterine Corpus That Are Progesterone Receptor Positive Compared With Those That Are Progesterone Receptor Negative | 68.9 percentage of participants |
p-value: 0.701Fisher Exact
Secondary
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.
Time frame: During the hysterectomy, which is 21-24 days after administration of depo-provera
Population: Eligible and Evaluable Patients (patients who had both an intake biopsy and hysterectomy)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PR Negative (<=0.2) | Change From Pre- to Post-treatment in Estrogren Receptor (ER) Expression | -0.77 Aggregate Score from Immunohistochemistr | Standard Error 0.14 |
p-value: <0.001Paired t-test
Secondary
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.
Time frame: During the hysterectomy , which is 21-24 days after administration of depo-provera
Population: Eligible and Evaluable Patients (patients who had both an intake biopsy and hysterectomy)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PR Negative (<=0.2) | Change From Pre- to Post-treatment in Progestrogren Receptor (PR) Expression | -1.12 Aggregate Score from Immunohistochemistr | Standard Error 0.15 |
p-value: <0.001Paired t-test