A Behavioral Intervention to Promote Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Endometrial Hyperplasia

Study Overview
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Brief Summary
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Up to 60% of endometrial cancer cases are attributed to obesity, in part because obesity promotes development of atypical endometrial hyperplasia (AEH), and up to 40% of women with AEH go on to develop endometrial cancer. The increasing prevalence of obesity in premenopausal women has resulted in increasing rates of AEH in this age group. Hysterectomy with removal of the fallopian tubes and ovaries is 100% effective in preventing endometrial cancer, but this approach results in infertility. Fertility-sparing treatments exist, such as treatment with oral or intrauterine progestin, but these treatments do not work uniformly and do not combat the underlying cause of endometrial cancer, which is obesity and metabolic syndrome. Additionally, up to 41% of women on progestin eventually experience relapse of AEH or endometrial cancer. Third, many patients have insulin resistance that may worsen with progestin therapy. Thus, to improve treatment of AEH and grade 1 endometrial cancer, prevent and reverse endometrial cancer, and allow women to preserve their fertility, the investigators must integrate an effective weight loss strategy to be given with progestin treatment. It is the hypothesis that premenopausal women with endometrial hyperplasia or grade 1 endometrial cancer who desire uterine preservation will be more likely to have atypia-free uterine preservation at two years if they receive progestin in combination with a behavioral weight loss intervention versus progestin plus enhanced usual care.

Official Title
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A Behavioral Intervention to Promote Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Endometrial Hyperplasia

Conditions
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Endometrial Hyperplasia, Grade 1 Endometrial Cancer

Intervention / Treatment
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* Behavioral: Telemedicine behavioral weight intervention
* Drug: Progestin
* Behavioral: Enhanced usual care
* Drug: Levonorgestrel-releasing IUD.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of histologically confirmed complex atypical endometrial hyperplasia or grade 1 endometrial cancer. Patients with a previous diagnosis of AEH or grade 1 endometrial cancer who are already being followed with conservative management with oral or LNG-IUD progestin therapy are eligible. For patients with a previous diagnosis of AEH or grade 1 endometrial cancer who have been placed on progestin prior to study entry, the duration of IUD or oral progestin use prior to trial entry should be less than or equal to 6 months. Premenopausal woman with a uterus. ECOG performance status of 0-2. At least 18 years of age and no more than 45 years of age. Interested in uterine preservation/fertility-sparing treatment. BMI ≥ 30 kg/m^2. Prior or current receipt of progestin is allowed as above. Willingness to undergo placement of LNG-IUD at the time of study entry. Prior or current receipt of metformin is allowed. Ability to understand and willingness to sign an IRB approved written informed consent document. Exclusion Criteria: Prior participation in a weight loss intervention trial within 3 months prior to date of registration. Current, active treatment for any malignant neoplasm with chemotherapy or radiation. Concomitant use of weight management drugs or drugs for short-term weight loss. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Pregnant and/or breastfeeding. Participants must have a negative serum pregnancy test within 7 days of date of registration. Contraindication to use of an IUD: Congenital or acquired uterine anomaly, including fibroids if they distort the uterine cavity PID, postpartum endometriosis, infected abortion in the last 3 months, acute cervicitis or vaginitis including bacterial vaginosis Acute liver disease, liver tumor (benign or malignant) Hypersensitivity to any component of the IUD (levonorgestrel, silicone, polyethylene) Known or suspected carcinoma of the breast.

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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss Intervention<br>The levonorgestrel-releasing IUD is used in this study as per standard care. The behavioral weight loss intervention consists of a telemedicine cognitive behavioral coaching program. At each session, patients will self-report weight, number of days they kept a food journal during the past week, average daily caloric intake for the week, number of days exercised for the week, total number of minutes of moderate physical activity, and average number of steps per day for the week. | Behavioral: Telemedicine behavioral weight intervention<br>* Weekly telephone calls during the first month, biweekly during the next 5 months, and then monthly for the last 7 months (13 months total). Each telephone session will be 30 minutes long.<br>Drug: Progestin<br>* Released via the levonorgestrel-releasing IUD.<br>Drug: Levonorgestrel-releasing IUD.<br>* Standard of care<br>|
| Active Comparator: Arm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual Care<br>The levonorgestrel-releasing IUD is used in this study as per standard care. Participants will be provided with 1- to 3-page handouts on topics including healthy eating, exercise, and behavioral eating strategies from materials provided on the American Cancer Society, Society of Gynecologic Oncology, and WebMD Nourish websites. These materials encourage weight loss through calorie counting, recording dietary intake, engaging in exercise programs, and using portion control strategies. If participants in the enhanced usual care group do not achieve atypia-free uterine preservation (i.e., have not resolved their hyperplasia or grade 1 endometrial cancer) by one year of enrollment and continue to desire uterine preservation with progestin treatment, they will cross over to receive the telemedicine behavioral intervention for the second year. | Behavioral: Enhanced usual care<br>* 1-3 page handouts<br>Drug: Levonorgestrel-releasing IUD.<br>* Standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with atypia-free biopsy with uterine preservation |  | At 2 years (or exit from study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of hyperplasia | Defined as the period of time in months/days from the first biopsy to show AEH or grade 1 endometrial cancer to the first biopsy that shows no evidence of hyperplasia or malignancy | Through completion of follow-up (estimated to be 4 years) | 
| Change in weight |  | From baseline to 2 years | 
| Change in Cancer Worry Impact Events Scale (CWIES) | The CWIES is a 15-item self-report measure evaluating stress reactions and traumatic experiences, specifically inquiring about cancer worry-specific distress. Range of values for each individual item will be a Likert Scale from 0-5. 0=not at all and 5=often. The higher the score, the more cancer-worry specific distress the participant has. | At enrollment, 12 months, and end of treatment (estimated to be 2 years) | 
| Atypia-free survival or endometrial cancer-free survival |  | Through completion of follow-up (estimated to be 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fertility-sparing, weight management, obesity, endometrial cancer, behavioral intervention, premenopausal endometrial hyperplasia, premenopausal endometrial cancer