Levonorgestrel-Releasing Intrauterine System in Treating Patients With Complex Atypical Hyperplasia or Grade I Endometrial Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well levonorgestrel-releasing intrauterine system works in treating patients with complex atypical hyperplasia or grade I endometrial cancer. High levels of estrogen can cause the growth of endometrial cancer cells. Progesterone can help balance the amount of estrogen present. Hormone therapy using levonorgestrel, a type of progesterone, may fight endometrial cancer by helping regulate hormone levels.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the efficacy of the levonorgestrel intrauterine device (IUD) (levonorgestrel-releasing intrauterine system) to treat complex atypical hyperplasia (CAH) and grade 1 endometrioid endometrial carcinoma (G1 EEC). II. To determine if response to therapy can be predicted based on the molecular profile of the tumor or by change in gene expression after therapy. SECONDARY OBJECTIVES: I. To assess quality of life outcomes in patients treated with levonorgestrel IUD. II. To document the toxicity profile of the levonorgestrel IUD in the treatment of complex atypical hyperplasia and grade 1 endometrioid endometrial cancer. III. To evaluate the molecular profile of the hysterectomy specimen of patients treated with the levonorgestrel IUD. Compare molecular profile in pretreatment tissue to hysterectomy tissue between responders and non-responders to levonorgestrel IUD therapy. IV. To evaluate long-term survival, disease status, and fertility outcomes in patients with levonorgestrel IUD. OUTLINE: Patients undergo placement of a levonorgestrel-releasing intrauterine system. After completion of study treatment, patients are followed up every 3 months for 1 year, and then periodically for up to 5 years.

Official Title
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A Phase II Study of the Levonorgestrel Intrauterine Device (Mirena) to Treat Complex Atypical Hyperplasia and Grade 1 Endometrioid Endometrial Carcinoma

Conditions
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Atypical Endometrial Hyperplasia, Stage I Uterine Corpus Cancer AJCC v7, Stage IA Uterine Corpus Cancer AJCC v7, Stage IB Uterine Corpus Cancer AJCC v7, Stage II Uterine Corpus Cancer AJCC v7

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Device: Levonorgestrel-Releasing Intrauterine System
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients with a diagnosis of complex atypical hyperplasia or endometrial biopsy within three months of study enrollment OR patients with a diagnosis of grade 1 endometrioid endometrial carcinoma on endometrial biopsy within three months of study enrollment in the presence of one or more of the following: 1)desire for future fertility 2)morbid obesity (body mass index > 40) 3)multiple co-morbidities (ASA Class 3 or 4) No prior treatment for diagnoses in inclusion criteria 1. Women of any racial or ethnic group. Ability to comply with endometrial biopsies every 3 months. Willing and able to sign informed consent. Age greater than 18 years. Exclusion Criteria: Diagnosis of grade 1 endometrioid endometrial carcinoma without the presence of one of the 3 criteria mentioned in inclusion criteria 1. Diagnosis of grade 2 endometrioid endometrial carcinoma or higher on endometrial biopsy or on dilation and curettage specimen. Evidence of extrauterine spread of disease on imaging or during surgical evaluation. Congenital or acquired uterine anomaly which distorts the uterine cavity. Acute pelvic inflammatory disease. Acute liver disease or previously diagnosed liver tumor (benign or malignant). Conditions associated with increased susceptibility to infections with microorganisms. Such conditions include, but are not limited to, AIDS, leukemia and IV drug abuse. Genital actinomycosis. Current carcinoma of the breast. Current pregnancy. Breastfeeding mothers.

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 (levonorgestrel-releasing intrauterine system)<br>Patients undergo placement of a levonorgestrel-releasing intrauterine system. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Device: Levonorgestrel-Releasing Intrauterine System<br>* Undergo placement of a levonorgestrel-releasing intrauterine system<br>* Other names: Mirena;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate at 12 Month | Will be defined as complete response or partial response based on the endometrial biopsy. | At 1 year | 
| Efficacy of the Levonorgestrel Intrauterine Device (IUD) | To determine the efficacy of the Levonorgestrel Intrauterine Device (IUD) to treat complex atypical hyperplasia (CAH) and grade 1 endometrioid endometrial carcinoma (G1 EEC), defined as complete regression disease. The primary efficacy endpoint was pathologic response rate (RR) at 12 months defined as complete response (CR) or partial response (PR). CR was defined as no evidence of cancer or hyperplasia with atypia in patients with (CAH) or EEC. PR was defined as CAH in patients with EEC. Progressive disease (PD) was defined as grade 2 endometrioid endometrial cancer or above in patients with EEC or the presence of any cancer in patients with CAH. | At 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Score Using the Short Form-36 (SF-36) Survey | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health); 2 summary scores (physical and mental component); and self evaluated change in health status (summary of health status). The score for subscale scores and 2 summary score is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Summary of health status is a 5-point Likert scale ranging from 0=much worse now to 4=much better now. Higher subscale and summary score reflect better health status. | At baseline, 3 month, 6 month, 9 month and 12 month |