Adding a GLP‑1 weight‑loss medicine to a levonorgestrel IUD for obese patients with endometrial precancer or low‑grade cancer

A Pilot Study to Estimate Early Clinical Efficacy Signals of a Glucagon-like Peptide 1 Receptor Agonist (GLP-1RA) Administration in Conjunction With Levonorgestrel Intrauterine Device (LNG-IUD) in Obese Patients With Endometrioid Intraepithelial Neoplasia

This Phase 2 trial will test whether giving a GLP‑1 weight‑loss medicine together with a levonorgestrel IUD helps obese adults with endometrial intraepithelial neoplasia or grade 1 endometrioid cancer who cannot or do not want a hysterectomy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: University of Florida (Academic / other)
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT07107334 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial enrolls adults with recent pathology showing endometrial intraepithelial neoplasia or grade 1 endometrioid endometrial adenocarcinoma who are obese (BMI ≥ 30) and are poor surgical candidates or seeking fertility preservation. Participants receive a levonorgestrel intrauterine device together with a glucagon‑like peptide‑1 receptor agonist and are followed with pathology review and imaging to look for early signs of treatment response. External pathology is confirmed in‑house before enrollment, and imaging is used to ensure no myometrial invasion or extrauterine spread. The trial focuses on safety and early clinical efficacy signals rather than definitive cure rates.

Who should consider this trial

Good fit: Adults age 18 or older with a pathology report within the past 3 months showing endometrial intraepithelial neoplasia or grade 1 endometrioid adenocarcinoma, BMI ≥ 30, no myometrial invasion or extrauterine disease on recent imaging, and who are either poor surgical candidates or wish to preserve fertility are ideal candidates.

Not a fit: Patients with higher‑grade or invasive disease, documented myometrial invasion or extrauterine spread, BMI under 30, or contraindications to GLP‑1 receptor agonists or levonorgestrel IUD are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could offer a non‑surgical, fertility‑sparing treatment that reduces or reverses precancerous or low‑grade cancer changes in obese patients.

How similar studies have performed: Levonorgestrel IUDs are an established fertility‑sparing option for EIN/grade 1 disease and GLP‑1 receptor agonists show weight‑loss and cancer‑risk reduction signals, but combining them as a treatment approach for endometrial precancer/low‑grade cancer is novel and unproven.

Eligibility criteria

Inclusion Criteria:

* 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):

  1. Multiple medical co-morbidities (defined as American Society of Anesthesiologists \[ASA\] score ≥ 3) at physician discretion
  2. 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.

Exclusion Criteria:

* 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.

Where this trial is running

Gainesville, Florida

• University of Florida — Gainesville, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Kaitlin Nicholson, MD — University of Florida
• Study coordinator: Stephanie Portillo

Conditions Endometrioid Endometrial Adenocarcinoma; Endometrial cancer; endometrial intraepithelial neoplasia; endometrial adenocarcinoma; Levonorgestrel IUD