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NCT Number: NCT07820358

Semaglutide, Weight Loss, and LNG-IUD for Conservative Treatment of Endometrial Atypical Hyperplasia and Grade 1 Endometrial Cancer

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

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Key information

Conditions

Endometrial Atypical Hyperplasia Body Weight Body Weight Changes Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia Endometrial Cancer Endometrial Cancer Stage I Endometrial Hyperplasia Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Fertility-Sparing Treatment (FST) Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Neoplasms Neoplasms by Site Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity & Overweight Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms Weight Loss

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Houston Methodist Sugar Land, Houston, Texas, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histological Diagnosis: Histologically confirmed endometrial atypical hyperplasia or FIGO grade 1 endometrioid Endometrial Cancer
  • Imaging eligibility (for patients with 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.
  • Treatment Rationale (at least one of the following must apply):
  • 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.
  • Medical inoperability: patients are considered a poor surgical candidate due to:

i. Class III obesity (BMI ≥40 kg/m²); or ii. ASA Physical Status Classification score ≥3.

  • Metabolic Profile: BMI ≥ 30 kg/m², or BMI 27-29.9 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea, or non-alcoholic fatty liver disease).
  • Progestin washout: patients with prior progestin exposure are eligible provided the following minimum washout periods have been observed.
  • Oral progestins: 7 days
  • Injectable, short acting: 14 days
  • Injectable, long acting: 6 months
  • Contraceptive implant: 28 days
  • LNG-IUD: 7 days after removal

Exclusion criteria

  • 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
  • Willingness and ability to participate in a structured weight loss program, including attendance at counseling sessions (in person or virtual) and adherence to dietary and physical activity goals.

Treatment and study plan

Semaglutide (Wegovy) weekly injection

Drug

Semaglutide 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)

Device

Levonorgestrel-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

Behavioral

A 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.

Primary outcomes

  1. Pathological Response Rate

    Time frame: 6 months

    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

Secondary outcomes

  1. Time to response

    Time frame: 12 months

    Time to response in months from treatment initiation to first documented histopathological regression

  2. Adverse events

    Time frame: 12 months

    Incidence and severity of adverse events, graded per NCI-CTCAE v5.0, including drug-related (semaglutide) and device-related (LNG-IUD) events

  3. Durable response rate

    Time frame: 12 months

    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.

  4. Disease progression rate

    Time frame: 12 months

    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.

  5. Recurrence rate

    Time frame: 12 months

    The proportion of participants who experience recurrence of endometrial atypical hyperplasia or endometrial cancer following an initial complete pathological response, assessed through 12 months from treatment initiation. Disease status will be assessed via hysteroscopy with endometrial sampling.

Other outcomes

  1. Body weight change

    Time frame: 12 months

    Change in body weight, measured in kilograms, from baseline to 6 and 12 months following treatment initiation.

  2. Body mass index (BMI) change

    Time frame: 12 months

    Change in body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, from baseline to 6 and 12 months following treatment initiation.

  3. Waist circumference change

    Time frame: 12 months

    Change in waist circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.

  4. Hip circumference change

    Time frame: 12 months

    Change in hip circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.

  5. Waist-to-hip ratio change

    Time frame: 12 months

    Change in waist-to-hip ratio, calculated as waist circumference divided by hip circumference, from baseline to 6 and 12 months following treatment initiation.

  6. Glycated Hemoglobin change

    Time frame: 12 months

    Change in glycated hemoglobin (HbA1c), measured as a percentage, from baseline to 6 and 12 months following treatment initiation.

  7. Weight-Related Quality of Life (WRQOL)

    Time frame: 12 months

    Change in weight-related quality of life, assessed using a validated WRQOL questionnaire, from baseline to 6 and 12 months following treatment initiation.

  8. Health-Related Quality of Life (HRQOL)

    Time frame: 12 months

    Change in health-related quality of life, assessed using a validated HRQOL questionnaire, from baseline to 6 and 12 months following treatment initiation.

Sponsors and collaborators

Lead sponsor

The Methodist Hospital Research Institute

Other

Registry information

Official study title

SEMAGLUTIDE, WEIGHT LOSS, AND INTRAUTERINE THERAPY FOR FERTILITY-SPARING AND CONSERVATIVE TREATMENT FOR ENDOMETRIAL ATYPICAL HYPERPLASIA AND EARLY-STAGE, GRADE 1 ENDOMETRIOID ENDOMETRIAL CANCER

Acronym: SWIFT

Important dates

Study start
2027
Primary completion
2028
Study completion
2031
First posted
Sep 15, 2026
Registry last updated
Sep 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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