Tirzepatide and Levonorgestrel IUD Therapy for EIN and Early-Stage Endometrial Cancer

NCT07812636 | Not Yet Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: PSCI-26-029
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm study will evaluate the feasibility, safety, and preliminary efficacy of tirzepatide in combination with standard levonorgestrel intrauterine device (LNG-IUD) therapy in patients with endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid endometrial carcinoma with co-existing obesity and metabolic risk factors. Participants will receive tirzepatide once weekly while continuing standard clinical management with an LNG-IUD. Treatment decisions will remain at the discretion of the treating physician. The primary objective is to evaluate pathologic response at approximately 6 months. Secondary objectives include changes in metabolic parameters, assessing the incidence and severity of adverse events of tirzepatide and LNG-IUD therapy, quality of life assessment, change in weight, and change in BMI.

Conditions

Grade 1 Endometrial Endometrioid Carcinoma; Endometrial Intraepithelial Neoplasia; Metabolic Comorbidities

Keywords

Tirzepatide; LNG-IUD

Outcome Measures

Primary Outcomes (1)

• Pathologic Response at 6 months from Cycle 1 Day 1

  Pathologic response will be assessed at Cycle 6 Day 28, approximately 6 months after Cycle 1 Day 1, using available clinical pathology specimens, as clinically indicated. For participants undergoing definitive surgical management, pathologic response may be assessed using the hysterectomy specimen. For participants not undergoing hysterectomy, pathologic response may be assessed using an endometrial biopsy or dilation and curettage (D\&C). Pathologic response will be categorized as complete response, partial response, stable disease, or progressive disease.

  At the end Cycle 6 Day 28 (Approximately 6 months from Cycle 1 Day 1with each cycle approximately 28 days)

Secondary Outcomes (5)

• Change in metabolic parameters

  At Baseline, Cycle 4 Day 1, and Cycle 6 Day 28 (each cycle is approximately 28 days)

• Assessing the Incidence and Severity of Adverse Events of Tirzepatide and LNG-IUD therapy

  Through study completion, an average of 9 months

• Quality of Life Assessment Utilizing Study 36-Item Short Form Health Survey (SF-36) Quality of Life Score

  Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28

• Change in Weight

  For a total of 6 months from Baseline to Cycle 6 Day 28. Weight will be collected at Baseline, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28 (each cycle is approximately 28 days)

• Change in BMI

  For a total of 6 months from Baseline to Cycle 6 Day 28. Weight will be collected at Baseline, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28 (each cycle is approximately 28 days)

Study Arms (1)

LNG-IUD and Tirzepatide Management

EXPERIMENTAL

Participants will receive tirzepatide in combination with standard clinical management with an LNG-IUD. Tirzepatide will be initiated at 2.5 mg subcutaneously once weekly. Dose escalation will occur according to the study protocol based on participant tolerability and treating physician discretion. Tirzepatide will be administered for approximately 6 months.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1 RA) that can promote weight loss and improve metabolic parameters in patients with obesity.

LNG-IUD and Tirzepatide Management

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histologically confirmed endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid EC
• BMI ≥ 30 kg/m2
• Presence of at least one obesity-associated metabolic comorbidity, including:
• a. Hypertension defined as: i. Documented diagnosis of hypertension, regardless of treatment status, documented in the medical records, or ii. Participants receiving antihypertensive therapy, or iii. BP ≥ 130/80 mmHg over 3 independent measurements, or iv. Single BP ≥ 160/100 mmHg b. Hyperlipidemia defined as: i. Documented diagnosis of hyperlipidemia, regardless of treatment status, documented in the medical record, or ii. Participants receiving lipid-lowering therapy, or iii. Triglycerides \> 200 mg/dL, or iv. LDL Cholesterol \> 130 mg/dL c. Type 2 Diabetes defined as: i. Documented diagnosis of Type 2 diabetes mellitus, regardless of treatment status, documented in the medical record, or ii. Receiving glucose-lowering therapy, or iii. Impaired glucose tolerance (Hgb A1c \> 6.0%) d. Diagnosed with sleep apnea
• For participants diagnosed with grade 1 endometrioid endometrial carcinoma: clinical stage 1A disease with MRI-confirmed myometrial invasion \< 50% and no evidence of metastatic disease
• For participants with EIN: no evidence of extrauterine disease based on clinically appropriate evaluation
• Ability to provide informed consent and comply with study procedures and follow-up

You may not qualify if:

• Mismatch repair-deficient (MMRd) tumors
• p53-abnormal tumors
• Known hypersensitivity or contraindication to either:
• Tirzepatide, or
• LNG-IUD
• Prior LNG-IUD in place at the time of EIN or endometrial cancer diagnosis
• Current systemic progestin therapy
• Current treatment with tirzepatide or another GLP-1 receptor agonist/GLP-1-GIP receptor agonist, or prior treatment with these agents within 1 month before study enrollment
• Type 1 diabetes or a history of pancreatitis, medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
• Pregnancy, breastfeeding, or intention to become pregnant during the study treatment
• Concurrent malignancy requiring active treatment (except non-melanoma skin cancer)
• Any medical, psychiatric, or social condition, that in the opinion of the investigator, would interfere with study participation or safety
• Participants with diabetic eye disease, including non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema
• Severe renal impairment, defined as eGFR \< 30 mL/min/1.73m2

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Endometrial Hyperplasia

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

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

Study Officials

• Shaina Bruce, MD

  Penn State Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Crystal Sowers

CONTACT

7175315471; PSCI-CTO@pennstatehealth.psu.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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All participants will receive tirzepatide in combination with standard clinical management with an LNG-IUD. Treatment decisions will remain at the discretion of the treating clinical team.

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: September 10, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 10, 2026

Record last verified: 2026-09

Locations

US (1)