The goal of this clinical trial is to learn if a combination treatment of a hormonal intrauterine device (LNG-IUD), semaglutide, and a structured weight loss program can treat endometrial atypical hyperplasia or grade 1 endometrioid endometrial cancer while preserving fertility in women of reproductive age with endometrial atypical hyperplasia (EAH) or FIGO grade 1 endometrioid endometrial cancer who wish to preserve their fertility. The main questions it aims to answer are:
* What proportion of participants achieve a complete pathological response after treatment? * How durable is the response at 12 months? * What effect does the treatment have on metabolic outcomes (weight, BMI, HbA1c) and quality of life?
Participants will:
* Receive an LNG-IUD * Receive semaglutide 2.4mg * Participate in a structured weight loss program * Undergo hysteroscopy with endometrial sampling to assess treatment response * Complete quality-of-life assessments at baseline, 6 months, and 12 months
Histological Diagnosis: Histologically confirmed endometrial atypical hyperplasia or FIGO grade 1 endometrioid Endometrial Cancer
Depth of myometrial invasion <50% confirmed by MRI or disease limited to the endometrium
No evidence of extrauterine or metastatic disease on imaging.
Desire for future fertility: Patient expresses a documented desire to preserve the uterus and future reproductive function, with explicit acknowledgment that fertility-sparing treatment is not standard of care for endometrial cancer.
Age ≥18 years
Negative pregnancy test at screening
Ability to provide written informed consent and comply with study procedures
Willingness to undergo genetic counseling and MMR/IHC tumor profiling
Single group
Semaglutide (Wegovy) weekly injection
DrugSemaglutide 2.4 mg administered subcutaneously once weekly, following standard dose-escalation protocol, for the duration of the 6-month active treatment period. Used off-label in this trial for its metabolic effects in combination with LNG-IUD, rather than as monotherapy for weight loss.
LNG-IUD (Progestin)
DeviceLevonorgestrel-releasing intrauterine device inserted at study baseline and maintained through the active treatment and follow-up periods, providing continuous local progestin delivery to the endometrium in combination with systemic semaglutide.
Structured Weight Loss Program
BehavioralA structured, protocol-defined weight loss program combining dietary counseling and physical activity guidance, delivered concurrently with pharmacologic and device-based treatment to support metabolic response, distinct from weight loss achieved through semaglutide alone.
Pathological Response Rate
Pathological Response Rate (PRR) defined as the rate of regression of atypical hyperplasia or carcinoma on histopathological examination of the 6-month (end-of-treatment) hysteroscopic sample
Time to response
Time to response in months from treatment initiation to first documented histopathological regression
Adverse events
Incidence and severity of adverse events, graded per NCI-CTCAE v5.0, including drug-related (semaglutide) and device-related (LNG-IUD) events
Durable response rate
The proportion of participants who achieve a complete pathological response and maintain that response, without evidence of disease recurrence or progression, through 12 months following treatment initiation. Durable response will be assessed via hysteroscopy with endometrial sampling.
Disease progression rate
The proportion of participants who experience disease progression, defined as an increase in histologic grade or stage of endometrial atypical hyperplasia or endometrial cancer, without ever achieving a complete pathological response, assessed through 12 months from treatment initiation. Disease status will be assessed via hysteroscopy with endometrial sampling.
Body weight change
Change in body weight, measured in kilograms, from baseline to 6 and 12 months following treatment initiation.
Body mass index (BMI) change
Change in body mass index (BMI), reported as weight in kilograms divided by height in meters squared (kg/m2) \[normal values: 18.5-24.9 kg/m2\], from baseline to 6 and 12 months following treatment initiation.
Waist circumference change
Change in waist circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.
Hip circumference change
Change in hip circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
