Tirzepatide in the Treatment of Endometrial Cancer

NCT07605247 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 102506
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is looking for a better way to treat pre-cancer or early-stage cancer in the lining of the uterus in women who are also overweight. Everyone in the study will receive the standard treatment, a Progesterone IUD (LNG-IUD). This device is put in the uterus and releases hormones to help fight the disease. We will add a new medicine, Tirzepatide, for some people. Tirzepatide is a shot that helps with weight loss and overall health. You will be placed into one of two groups by chance (like flipping a coin):

1. 1.Group 1: You get the Progesterone IUD PLUS the Tirzepatide shot.
2. 2.Group 2: You get the Progesterone IUD ONLY (Standard Treatment).

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Quality of Life Quality of life will be measured through PROMs at the time points listed below for explorative purposes.

  Quality of life will be measured through PROMs at the time points listed below for explorative purposes.

  ● Screening (day -30 to Week 0) ● 3 months (Visit 4, Week 12) ● 6 months (Visit 7, Week 24) ● 9 months (Visit 10, Week 36)

Study Arms (1)

LNG-IUD + Tirzepatide

EXPERIMENTAL

This is a multicenter, open-label, prospective, single-arm phase II pilot trial using a sequential design to evaluate the addition of tirzepatide to LNG-IUD in women with obesity and premalignant or early-stage endometrioid endometrial pathology.

Drug: Tirzepatide; Device: LNG-IUD plus tirzepatide

Interventions

Tirzepatide DRUG

Phase I (Months 0-3): All participants receive LNG-IUD alone

LNG-IUD + Tirzepatide

LNG-IUD plus tirzepatide DEVICE

Phase II (Months 3-9): All participants continue LNG-IUD plus tirzepatide (titrated to maximally tolerated dose).

LNG-IUD + Tirzepatide

Eligibility Criteria

• Age: 18 Years - 99 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed endometrial intraepithelial neoplasia (EIN), FIGO grade 1 or 2 endometrioid adenocarcinoma on a curette or endometrial biopsy. \*EIN patients capped at a maximum of 50% of total enrollment ((≤10 patients). .
• P53 wild-type and MMR proficient (or microsatellite stable) confirmed by immunohistochemistry.
• Females with a BMI \> 27 kg/m2 are at high risk of surgical complications due to comorbidities (diabetes, hypertension, cardiovascular disease, obstructive sleep apnea) or BMI \> 30 kg/m2 with no comorbidities and have decided not to opt for immediate surgical intervention (having been advised that this is the standard of care);
• Over 18 years of age at time of randomization;
• CT scan of pelvis, abdomen, and chest (or chest X-Ray), suggesting the absence of extrauterine disease in patients with endometrial cancer only;
• Myometrial invasion on MRI of not more than 50%;
• No lymph vascular invasion on biopsy;
• Serum CA125 ≤35 U/mL;
• No known hypersensitivity or contraindications for LNG-IUD (severe liver disease, personal history of breast cancer, active pelvic inflammatory disease, congenital uterine abnormality) or GLP-1 agonist;
• Ability to comply with endometrial biopsies at specified 3-monthly intervals;
• Negative serum or urine pregnancy test in pre-menopausal women and women \< 2 years after the onset of menopause;
• No LNG-IUD or LNG-IUD inserted \< 6 weeks prior to enrollment;
• Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol.

You may not qualify if:

• \. ECOG performance status ≥3 (Appendix II); 2. Grade 1 or 2 endometrioid adenocarcinoma of the endometrium with myometrial invasion deeper than 50% on MRI, or any patients with grade 3 endometrioid adenocarcinoma; 3. MMR deficient or p53 mutated endometrial cancer; 4. Histological (cell) type other than endometrioid adenocarcinoma (sarcomas or high-risk endometrial e.g., papillary serous, clear cell); 5. Pregnant or planning to become pregnant during trial period; 6. Prior treatment for EAC; 7. Patients with a history of pelvic or abdominal radiotherapy; 8. Unwilling to have additional endometrial biopsies or unable to attend monthly clinical assessments; 9. Unable to provide informed consent or complete questionnaires; 10. Evidence of extra-uterine extension on cross-sectional imaging; 11. Congenital or acquired uterine anomaly that distorts the uterine cavity; 12. Acute pelvic inflammatory disease; 13. Genital actinomycosis; 14. History of pancreatitis; 15. Diagnosis of Type 1 diabetes; 16. Previous treatment with GLP-1 receptor agonists within the last 3 months; 17. Visit 1 thyroid-stimulatory hormone outside of the range of 0.4-6.0 mL/uL; 18. Obesity induced by other endocrine disorders (e.g., Cushing syndrome); 19. Current or history of treatment with medications that may cause significant weight gain within 3 months prior to screening visit, including systemic corticosteroids (except for a short course of treatment, i.e., 7-10 days or physiologic replacement doses ≤10 mg/day prednisone equivalent), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g., imipramine, amitriptyline, mirtazapine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium); 20. Participation in a clinical trial of weight control within the last 3 months before screening for this trial; 21. Previous surgical treatment for obesity (excluding liposuction if performed \>1 year before study entry); 22. History of major depressive disorder or a PHQ-9 \>15 within the last 2 years (completed at visit 1) or history of other severe psychiatric disorders (e.g., schizophrenia or bipolar disorder) or diagnosis of an eating disorder such as restrained eating, binge eating, or bulimia (based on Questionnaire for Diagnosing Binge Eating Disorder and Bulimia Nervosa completed at visit 1); 23. Participants with a lifetime history of a suicide attempt or history of any suicidal behavior within the past month before entry into the trial; 24. Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the Investigator; 25. Impaired liver function, defined as screening aspartate aminotransferase or alanine aminotransferase ≥ 2.5 times the upper normal range (one re-test analyzed at the local laboratory within 1 week prior to screening is permitted, with the last sample being conclusive); 26. Impaired renal function is defined as serum creatinine ≥ 1.72 mg/dl (1 retest within 1 week prior to screening through the local laboratory is permitted, with the result of the last sample conclusive); 27. Known clinically significant active cardiovascular disease, including history of unstable angina, acute coronary event, other significant cardiac events (including history of arrhythmias, myocardial infarction (MI), or conduction delays on electrocardiogram \[ECG\]), or cerebral stroke within the past 6 months and/or heart failure (New York Heart Association \[NYHA\] Class III or IV) at the discretion of the Investigator; 28. Uncontrolled treated/untreated hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg). If white-coat hypertension is suspected at the screening visit, a repeated measurement at run-in before other trial-related activities is allowed; 29. Known history of substance abuse; 30. Language barrier, mental incapacity, unwillingness, or inability to understand and complete the mental health questionnaire in the provided language; 31. History of breast, thyroid or colon cancer. Patients with any prior diagnosis of thyroid cancer are not eligible for this study 32. Current other cancer. Patients with any current malignancy or past malignancy in the past 5 years are not eligible. Excluded are treated basal cell carcinoma or squamous cell carcinoma. (past or present, except basal cell skin cancer or squamous cell skin cancer). Patient who have received any active treatment for another malignancy within 2 years prior to enrollment are not eligible); 33. Breastfeeding mothers

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead

MeSH Terms

Conditions

Endometrial Neoplasms

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

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

Central Study Contacts

Eugenia Girda, MD

CONTACT

732-235-2465; eg535@cinj.rutgers.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Obstetrics, Rutgers Robert Wood Johnson Medical School

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: May 22, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05