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

NCT ID: NCT07078838

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-04-30
• Study Completion Date: 2029-03-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

tirzepatide

The treatment arm will receive 5mg tirzepatide for 4 weeks prior to standard of care surgery.

Group Type: EXPERIMENTAL

Tirzepatide

Intervention Type: DRUG

Patients will receive a subcutaneous dose of 5 mg weekly for the 4 weeks prior to surgical staging.

No tirzepatide

No tirzepatide arm will not receive tirzepatide, and Standard Operating Procedures will be applied.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Tirzepatide

Patients will receive a subcutaneous dose of 5 mg weekly for the 4 weeks prior to surgical staging.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• Histological or cytological evidence/confirmation of endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid histology endometrial cancer (EC) and scheduled to undergo standard of care hysterectomy and staging.
• Subject must have archival EC tissue available.
• Body mass index of >30kg/m2
• Demonstrate adequate organ function as defined in the protocol, all screening labs to be obtained within 28 days prior to initiating study treatment

Exclusion Criteria

• 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.
• Have type 1 diabetes mellitus or latent autoimmune diabetes in adults, or are receiving treatment with insulin.
• Have a history of severe hypoglycemia or not be able to communicate an understanding of hypoglycemic symptoms.
• Have a history of acute or chronic pancreatitis or serum lipase/amylase >2X ULN or fasting triglyceride >500 mg/dL at screening.
• Have a diagnosis of gastroparesis, history of bariatric surgery, or a clinically significant gastric emptying abnormality.
• Have a history or family history of multiple endocrine neoplasia, thyroid C-cell hyperplasia, or medullary thyroid carcinoma.
• Currently receiving another treatment for EIN or EC.
• Any condition, in the opinion of the investigator, which would prohibit safe participation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victoria Bae-Jump

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Countries

United States

Central Contacts

Chelsea Baker

Role: CONTACT

chelsea_baker@med.unc.edu

(919)-843-5230

Tamara Pfeffer

Role: CONTACT

tamara_pfeffer@med.unc.edu

+1 919-966-4432

Related Links

http://unclineberger.org/patientcare/clinical-trials/clinical-trials

UNC Lineberger Comprehensive Cancer Center Clinical Trials

Other Identifiers

U01CA281026

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LCCC2502

Identifier Type: -

Identifier Source: org_study_id