An official website of the United States government
A Behavioral Weight loss Intervention with Levonorgestrel Intrauterine Device to Promote Primary Prevention and Uterine Preservation in Premenopausal Women with Obesity and Atypical Endometrial Hyperplasia or Grade I Endometrial Cancer, UPLifT-Endo Trial
Trial Status: active
This phase II trial compares the effect of a behavioral weight-loss intervention with a levonorgestrel intrauterine device (LNG-IUD) to usual care with LNG-IUD on prevention and uterine preservation in premenopausal women with obesity and atypical endometrial hyperplasia (AEH) or grade I endometrial cancer (EC). Up to 60% of endometrial cancer cases are related to obesity, in part because obesity promotes the development of atypical endometrial hyperplasia, 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. Behavioral interventions, such as behavioral weight management coaching, use techniques to help patients change the way they react to environmental triggers that may cause a negative reaction and have been shown to improve weight loss in primary care settings. An LNG-IUD is a small T-shaped device that is inserted into the uterus that slowly releases a progestin (levonorgestrel) hormone into the uterus that may help block the formation of growths that could become cancer. Adding a behavioral weight loss intervention to treatment with LNG-IUD may result in greater uterine preservation and improve quality of life in women with obesity and AEH or grade 1 EC.
Inclusion Criteria
Diagnosis of histologically confirmed complex AEH 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 documented
Premenopausal woman with a uterus
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
At least 18 years of age and no more than 45 years of age
Undergoing uterine-sparing management (e.g. due to interest in fertility preservation, interest in uterine preservation, provider recommendation, or other reason)
Body mass index (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
Ability to understand and willingness to sign an institutional review board (IRB) approved written informed consent document
Exclusion Criteria
Current, active treatment for any malignant neoplasm with chemotherapy or radiation
Pregnant and/or breastfeeding. Participants must have a negative urine or serum pregnancy test during screening window and within 7 days prior to LNG-IUD insertion. If LNG-IUD is in place, lack of pregnancy is assumed
Active pelvic infection at the time of IUD placement or other contraindication to the use of an IUD in the opinion of the treating physician
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05903131.
I. To determine the efficacy of progestin (LNG-IUD) plus a behavioral weight loss intervention in allowing uterine preservation in premenopausal women with AEH or grade 1 endometrial cancer (EC) compared to LNG-IUD alone.
SECONDARY OBJECTIVE:
I. To determine the effect of the combination of progestin plus a behavioral weight loss intervention on time to resolution of AEH, time to resolution of AEH for AEH patients and of EC for grade 1 EC patients, AEH-free survival (atypia-free survival [AFS]), following any resolution, EC progression-free survival (EC-PFS) following any resolution, weight change, and quality of life compared to progestin alone.
EXPLORATORY OBJECTIVES:
I. To determine pregnancy rates of the combination of progestin plus a behavioral weight loss intervention compared to progestin alone.
II. To determine the effect of the combination of progestin plus a behavioral weight loss intervention compared to progestin alone on endometrial and metabolomics biomarkers.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (BEHAVIORAL INTERVENTION): Patients undergo placement of LNG-IUD at baseline and participate in cognitive behavior therapy coaching telephone calls over 30 minutes weekly for 1 month, biweekly for 5 months, and then monthly for 6 months. Additionally, patients undergo blood sample collection at baseline and on study.
ARM II (ENHANCED USUAL CARE): Patients undergo placement of LNG-IUD at baseline and receive counseling and educational handouts on topics including healthy eating, exercise, and behavioral eating strategies over 24 months. Patients also undergo blood sample collection at baseline and on study. Additionally, patients who do not achieve atypia-free uterine preservation at the end of 12 months may cross over to the telemedicine behavioral intervention for the second year.
After completion of study intervention, patients are followed up every 3 months for up to 24 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
