Endometrioid Endometrial Adenocarcinoma
Conditions
Keywords
Endometrial cancer, endometrial intraepithelial neoplasia, endometrial adenocarcinoma, Levonorgestrel IUD
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.
Interventions
DRUGGlucagon-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 agonist 2 weeks before any elective surgical procedure.
Sponsors
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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): 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time from start of GLP-1RA to clearance of staging hysterectomy | 12 months | Determine the time from start of GLP-1RA treatment to clearance for staging hysterectomy in patients with poor surgical candidacy for a hysterectomy. |
| Time from start of GLP-1RA to clearance for pregnancy pursuit | 12 months | Determine the time from start of GLP-1RA treatment to clearance for pregnancy pursuit in patients pursuing fertility sparing. |
| Endometrial pathologic response | 6 months after beginning GLP-1RA treatment | Determine the endometrial pathologic response 6 months after beginning GLP-1RA treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of surgery | Intraoperative | Determine the length of staging hysterectomy surgery |
| Number of nights in hospital | 12 months | Determine the number of nights spent in the hospital for staging hysterectomy |
| Postoperative complications | 12 months | Determine the postoperative complications following staging hysterectomy |
| Patient-reported quality of life | 6 months | Compare patient-reported quality of life, as measured by the EORTC QLQ-C30, v3.0 between baseline and at 6 months after beginning GLP-1RA treatment |
Countries
United States
Contacts
CONTACTStephanie Portillo
PRINCIPAL_INVESTIGATORKaitlin Nicholson, MD
University of Florida
Outcome results
None listed