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

Official title

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

Overview

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.

Interventions

• Drug Glucagon-like peptide 1 receptor agonist
  Subjects will receive a glucagon-like peptide 1 receptor agonist (either semaglutide, tirzepatide or liraglutide) by self-injection or orally (semaglutide or orforglipron) 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

Primary outcome measures

• Time from start of GLP-1RA to clearance of staging hysterectomy [Time frame: 12 months]
• Time from start of GLP-1RA to clearance for pregnancy pursuit [Time frame: 12 months]
• Endometrial pathologic response [Time frame: 6 months after beginning GLP-1RA treatment]
• Endometrial pathologic response [Time frame: 12 months after beginning GLP-1RA treatment]

Secondary outcome measures (6)

• Length of surgery [Time frame: Intraoperative]
• Number of nights in hospital [Time frame: 12 months]
• Postoperative complications [Time frame: 12 months]
• Patient-reported quality of life [Time frame: 6 months]
• Patient-reported quality of life [Time frame: 12 months]
• Patient-reported quality of life [Time frame: at either clearance for pregnancy pursuit or staging hysterectomy, which will ideally occur by 12 months after beginning study treatment]

Eligibility criteria

Inclusion criteria

• Adults ≥ 18 years old
• A pathological diagnosis with in the past 4 months consistent with grade 1 endometrioid endometrial adenocarcinoma or EIN
• 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
• For those with endometrial cancer, no extrauterine involvement or myometrial invasion by MRI (preferred) or transvaginal ultrasound
• 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 or via investigator confirmation.
• 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)
• 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 known current or history of hormonally- sensitive carcinoma (e.g., breast, melanoma)
• Subjects actively taking GLP-1RA for more than 14 days at time of consent.
• Subjects with levonorgestrel-releasing intrauterine system placed >45 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Florida — Gainesville

Identifiers

NCT: NCT07107334 · UF-GYN-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗