Tirzepatide in Obesity-Driven Endometrial Cancer

NCT07065552 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: LCCC2415
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

LCCC2415 examines the antiproliferative effect of tirzepatide on the endometrium of endometrial cancer (EC). This is a pre-operative window clinical study. Endometrial biopsy samples from patients before tirzepatide treatment will be compared to their post-intervention hysterectomy specimens. If archival tissue is unavailable, a fresh biopsy will be taken before tirzepatide treatment. Post-intervention tissue will be collected from the hysterectomy specimen. The hypothesis is that tirzepatide's anti-tumorigenic effects are due to both an improvement in the host's metabolic milieu (indirect effect) and a direct effect on the EC tumor microenvironment via the inter-related pathways of insulin, lipid, and mTOR signaling. Therefore, tirzepatide may be an innovative approach to effectively induce weight loss and inhibit tumor growth in EC, the most obesity-driven of all cancers.

Conditions

Endometrial Cancer; Obesity

Keywords

tirzepatide; tumor microenvironment; insulin; lipid; mTOR signaling

Outcome Measures

Primary Outcomes (1)

• Change in Proliferation

  Change in Proliferation will be determined by immunohistochemical ( Ki-67 staining) analysis pre- (baseline) and post-tirzepatide treatment hysterectomy samples (at the time of surgery and end of treatment). The percentage of tumor cells that are positive for Ki-67, indicating they are in the active phases of the cell cycle (not resting). Low Ki-67 (\<10-15%): Slower-growing tumor. Intermediate (15-30%): Moderately proliferative. High (\>30%): Fast-growing, potentially more aggressive.

  Baseline - Up to 6 weeks

Secondary Outcomes (13)

• Improvement in Diabetes

  Baseline - Up to 6 weeks

• Improvement in HgbA1C level

  Baseline - Up to 6 weeks

• Improvement in waist-to-hip ratio

  Baseline - Up to 6 weeks

• Improvement in Body Mass Index

  Baseline - Up to 6 weeks

• Change in circulating levels of inflammatory cytokines

  Baseline - Up to 6 weeks

Study Arms (1)

endometrial carcinoma

EXPERIMENTAL

Obese women with endometrial carcinoma are included.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Tirzepatide will be administered once weekly, subcutaneously, and patients will be taught how to administer this drug at home. Patients will be started on a dose of 5 mg tirzepatide weekly for four weeks prior to surgical staging. .

endometrial carcinoma

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current diagnosis of endometrioid histology cancer and scheduled to undergo hysterectomy and staging.
• Agree to comply with all required study assessments and visits including internet capabilities.
• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
• Age ≥ 18 at the time of consent.
• Body mass index of ≥30 kg/m2.
• Presumed clinically early-stage disease (disease confined to uterus only).
• ECOG ≤ 2 or Karnofsky Performance Status of \> 50

You may not qualify if:

• Active infection requiring systemic therapy.
• Subject is pregnant or breast feeding.
• Taking any prescription medications or other drugs that may influence metabolism per discretion of investigator.
• Taking a central nervous system stimulant.
• Current psychological conditions that would be incompatible with participation in this study, as determined by investigator.
• 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 receiving treatment with insulin.
• Have a history of severe hypoglycemia or not be able to communicate an understanding of hypoglycemic symptoms.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• UNC Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Endometrial Neoplasms; Obesity; Insulin Resistance

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Bae-Jump Victoria, MD PhD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luz Cuaboy

CONTACT

+1 919-966-4432; luz_cuaboy@med.unc.edu

Emmie Cole

CONTACT

+1 919-966-4432; emmie_cole@med.unc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: July 15, 2025
• Study Start: April 27, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (1)