NCT07078838

Tirzepatide in Women With Obesity and Endometrial Intra-epithelial Neoplasia or Grade 1 Endometrial Cancer

A Randomized, Window of Opportunity Trial of Tirzepatide in Women With Obesity and a Diagnosis of Endometrial Intra-epithelial Neoplasia (EIN) or Grade 1 Endometrial Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Endometrial Cancer
• Endometrial Intraepithelial Neoplasia
• Grade 1 Endometrial Endometrioid Carcinoma

Interventions

Type	Name	Description
DRUG	Tirzepatide	Patients will receive a subcutaneous dose of 5 mg weekly for the 4 weeks prior to surgical staging.

Timeline

• Start date: 2026-04-01
• Primary completion: 2029-03-01
• Completion: 2029-03-01
• First posted: 2025-07-22
• Last updated: 2026-01-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study