NCT05903131

Brief Summary

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 AEH desire uterine preservation will be more likely to have atypia-free uterine preservation at one year if they receive progestin in combination with a behavioral weight loss intervention versus progestin plus enhanced usual care.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
96

participants targeted

Target at P50-P75 for phase_2

Timeline
42mo left

Started Oct 2024

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress31%
Oct 2024Oct 2029

First Submitted

Initial submission to the registry

May 24, 2023

Completed
22 days until next milestone

First Posted

Study publicly available on registry

June 15, 2023

Completed
1.4 years until next milestone

Study Start

First participant enrolled

October 24, 2024

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2028

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2029

Last Updated

January 20, 2026

Status Verified

January 1, 2026

Enrollment Period

4 years

First QC Date

May 24, 2023

Last Update Submit

January 16, 2026

Conditions

Endometrial HyperplasiaGrade 1 Endometrial Cancer

Keywords

fertility-sparingweight managementobesityendometrial cancerbehavioral interventionpremenopausal endometrial hyperplasiapremenopausal endometrial cancer

Outcome Measures

Primary Outcomes (1)

  • Number of participants with atypical endometrial hyperplasia (AEH)-free biopsy

    At 1 year

Secondary Outcomes (6)

  • Time to resolution of atypical endometrial hyperplasia (AEH)

    Through completion of follow-up (estimated to be 2 years)

  • Time to resolution of endometrial cancer

    Through completion of follow-up (estimated to be 2 years)

  • Atypia-free survival

    Through completion of follow-up (estimated to be 2 years)

  • Endometrial cancer progression-free survival (EC-PFS)

    Through completion of follow-up (estimated to be 2 years)

  • Change in weight

    Through completion of follow-up (estimated to be 2 years)

  • +1 more secondary outcomes

Study Arms (2)

Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss Intervention

EXPERIMENTAL

* 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 interventionDrug: ProgestinDrug: Levonorgestrel-releasing IUD.

Arm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual Care

ACTIVE COMPARATOR

* 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. * The participants randomized to this arm will cross over to the behavioral weight loss intervention arm at 12 months if they have not achieved resolution of AEH or grade 1 endometrial cancer.

Behavioral: Enhanced usual careDrug: Levonorgestrel-releasing IUD.

Interventions

ProgestinDRUG

Released via the levonorgestrel-releasing IUD.

Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss Intervention
Telemedicine behavioral weight interventionBEHAVIORAL

Weekly telephone calls during the first month, biweekly during the next 5 months, and then monthly for the last 7 months (12 months total). Each telephone session will be 30 minutes long.

Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss Intervention
Enhanced usual careBEHAVIORAL

1-3 page handouts

Arm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual Care
Levonorgestrel-releasing IUD.DRUG

Standard of care

Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss InterventionArm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual Care

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of histologically confirmed complex atypical endometrial hyperplasia (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.
  • 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).
  • 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 IRB approved written informed consent document.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

University of New Mexico

Albuquerque, New Mexico, 87106, United States

RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Related Links

MeSH Terms

Conditions

Endometrial HyperplasiaObesityEndometrial Neoplasms

Interventions

Progestins

Condition Hierarchy (Ancestors)

Uterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesOverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsUterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasms

Intervention Hierarchy (Ancestors)

HormonesHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and Uses

Study Officials

  • Andrea R Hagemann, M.D., MSCI

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea R Hagemann, M.D., MSCI

CONTACT

314-362-1763hagemanna@wustl.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 24, 2023

First Posted

June 15, 2023

Study Start

October 24, 2024

Primary Completion (Estimated)

October 31, 2028

Study Completion (Estimated)

October 31, 2029

Last Updated

January 20, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(3)