A Study to Estimate Early Clinical Efficacy Signals of GLP-1 Agonist Administration in Conjunction With Levonorgestrel Intrauterine Device in Obese Patients With Endometrioid Intraepithelial Neoplasia

NCT07107334 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UF-GYN-003
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will explore the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) used concurrently with levonorgestrel intrauterine device in patients with poor surgical candidacy for a hysterectomy or patients who are pursuing fertility sparing. GLP-1RA are a class of medications that mimic the natural hormone glucagon-like peptide-1. These medications trigger the pancreas to release insulin which can help lower blood sugar levels and delay gastric emptying. The recent FDA approval of GLP-1RAs has changed the landscape for pharmacotherapy for weight loss. These hormone-based obesity medications are novel and revolutionary in obesity medicine. Liraglutine, semaglutide, and tirzepatide have become exceedingly popular for their effects on weight loss and obesity-related comorbidities. More recently, GLP-1RAs have exhibited risk reduction of various obesity associated cancers, including endometrial cancer but their exact role in prevention and treatment has yet to be measured.

Conditions

Endometrioid Endometrial Adenocarcinoma

Keywords

Endometrial cancer; endometrial intraepithelial neoplasia; endometrial adenocarcinoma; Levonorgestrel IUD

Outcome Measures

Primary Outcomes (4)

• Time from start of GLP-1RA to clearance of staging hysterectomy

  Determine the time from start of GLP-1RA treatment to clearance for staging hysterectomy in patients with poor surgical candidacy for a hysterectomy.

  12 months

• Time from start of GLP-1RA to clearance for pregnancy pursuit

  Determine the time from start of GLP-1RA treatment to clearance for pregnancy pursuit in patients pursuing fertility sparing.

  12 months

• Endometrial pathologic response

  Determine the endometrial pathologic response 6 months after beginning GLP-1RA treatment

  6 months after beginning GLP-1RA treatment

• Endometrial pathologic response

  Determine the endometrial pathologic response 12 months after beginning GLP-1RA treatment

  12 months after beginning GLP-1RA treatment

Secondary Outcomes (6)

• Length of surgery

  Intraoperative

• Number of nights in hospital

  12 months

• Postoperative complications

  12 months

• Patient-reported quality of life

  6 months

• Patient-reported quality of life

  12 months

Study Arms (1)

Glucagon-like peptide 1 receptor agonist

EXPERIMENTAL

Drug: Glucagon-like peptide 1 receptor agonist

Interventions

Glucagon-like peptide 1 receptor agonist DRUG

Subjects will receive a glucagon-like peptide 1 receptor agonist (either semaglutide, tirzepatide or liraglutide) by self-injection or orally (for semaglutide only) for as clinically indicated by the treating physician or until the subject receives clearance for staging hysterectomy or for pregnancy pursuit. The choice of glucagon-like peptide 1 receptor agonist for each subject will be at the treating physician's discretion. Subjects will discontinue the glucagon-like peptide 1 receptor agonist 2 weeks before any elective surgical procedure.

Glucagon-like peptide 1 receptor agonist

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years old
• A pathological diagnosis with in the past 3 months consistent with grade 1 endometrioid endometrial adenocarcinoma or endometrial intraepithelial neoplasia
• For subjects with a diagnosis of endometrial intraepithelial neoplasia/grade 1 endometrioid endometrial adenocarcinoma prior to enrollment in the study, and with a diagnosis made outside this institution, the diagnostic material originating from outside the study site will undergo in-house pathology review before enrollment acceptance.
• ECOG Performance Status of 0 to 3
• No extrauterine involvement or myometrial invasion by MRI (preferred) or transvaginal ultrasound with in the last 3 months
• BMI ≥ 30 kg/m2 and one of the following (per medical record or self-report):
• Multiple medical co-morbidities (defined as American Society of Anesthesiologists \[ASA\] score ≥ 3) at physician discretion
• Fertility desire
• Subject has had appropriate age-related breast examinations and imagining prior to study enrollment, as documented in the medical record.
• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.

You may not qualify if:

• Subjects with grade 2 or 3 endometroid or any non-endometrioid histology (i.e., clear cell, carcinoma, serous)
• Subjects whose tumors are estrogen receptor negative
• Clinical suspicion of metastatic disease as assessed by the treating physician or confirmed metastatic disease based on imaging
• Subjects with abnormal cervical cytology
• Subjects who are diagnosed with thyroid cancer, pancreatitis, or multiple endocrine neoplasia syndrome type 2
• Subjects who are confirmed to be pregnant or breastfeeding
• History of medullary thyroid cancer
• Subjects with levonorgestrel-releasing intrauterine system placed \>14 days prior to study enrollment.
• Subjects must not have more than one active malignancy at the time of enrollment (Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with safety or efficacy assessment of the study \[as determined by the treating physician or approved by the PI\] may be included).
• History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician. This includes, but is not limited to, conditions such as New York Heart Association (NYHA) Class IV heart failure.
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32608, United States

RECRUITING

MeSH Terms

Conditions

Endometrial Neoplasms; Endometrial Hyperplasia

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Kaitlin Nicholson, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Portillo

CONTACT

352-273-3650; portillos@ufl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: August 6, 2025
• Study Start: April 7, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2029
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)