The goal of this study is to determine the anti-proliferative effect of tirzepatide on the endometrium of patients with endometrial intra-epithelial neoplasia (EIN) and Grade 1 endometrial cancer (EC), by comparing archival endometrial biopsy samples of patients randomized to tirzepatide versus SOC (no tirzepatide) to their post-intervention hysterectomy specimens.
It was hypothesized that tirzepatide may help fight tumors in two ways: indirectly, by improving the body's overall metabolic health, and directly, by acting on abnormal cells in the uterus, such as those found in endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC). EIN is considered a precursor to EC. Tirzepatide may influence the tumor environment through key biological pathways related to insulin, fat metabolism, and mTOR signaling, all of which are often disrupted in individuals with obesity. Because both EIN and EC are strongly linked to obesity, tirzepatide could offer a promising dual benefit, promoting weight loss while also slowing or stopping tumor growth. The primary goal of this study is to determine whether tirzepatide can reduce cell proliferation in the lesions or tumors of patients with EIN and early- stage (Grade 1) EC.
Patients will either be randomized to receive tirzepatide or no tirzepatide for 4 weeks prior to their hysterectomy surgery. Patients randomized to the tirzepatide arm will be given a glucose monitoring system for continuous monitoring with real-time alarms to alert of hypoglycemia. Patients will complete diaries during treatment to document compliance with medication and record any side effects.
Patients will undergo standard of care surgery 7-10 days after the final dose of tirzepatide in order to minimize the risk of gastroparesis. During surgery (hysterectomy), an endometrial biopsy for uterine biopsy tissue will be collected.
At the 1-month post-operation visit, patients from both arms will be referred to an institutional weight loss clinic.
Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
The subject is willing and able to comply with study procedures based on the judgement of the investigator.
Age > 18 years at the time of consent.
ECOG ≤ 2 or Karnofsky Performance Status of >50
Active infection requires systemic therapy.
Subject is pregnant or breast breastfeeding, or planning to become pregnant at any time during the study
Taking any prescription medications or other drugs that influence weight change in the past 3 months.
Known sensitivities (i.e., urticaria and eczema) to GIP and GLP-1 receptor agonists.
Parallel
Tirzepatide
DrugPatients will receive a subcutaneous dose of 5 mg weekly for the 4 weeks prior to surgical staging.
Anti-proliferative effect of Tirzepatide
Anti-proliferative effect of Tirzepatide will be measured via Immunohistochemistry analysis using multi-color fluorescence assays to assess Ki-67 staining.
The Ki-67/caspase-3 ratio change
The Ki-67/caspase-3 ratio will be assessed via immunohistochemistry, before and after treatment in the 2 groups. It is expected that the ratio will exhibit stronger intervention effects since proliferation should decrease and apoptosis should increase.
Response to treatment
Response to treatment will be defined as a decrease of ≥13% in proliferation of the endometrium (EIN and EC) from pre- to post-treatment.
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UNC Lineberger Comprehensive Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
