Clinical trial · Interventional
Tirzepatide and Levonorgestrel IUD Therapy for EIN and Early-Stage Endometrial Cancer
Combination Tirzepatide and Levonorgestrel Intrauterine Device Therapy for Endometrial Intraepithelial Neoplasia (EIN) and Grade 1 Endometrioid Endometrial Carcinoma: A Pilot Window-of-Opportunity Study
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 11, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260911-000001
Summary
Brief summary (as posted)
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
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Endometrial Intraepithelial Neoplasia | Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia | ALIAS | 0.90 |
| Grade 1 Endometrial Endometrioid Carcinoma | FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma | ALIAS | 0.90 |
| Metabolic Comorbidities | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Tirzepatide | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- LNG-IUD and Tirzepatide Management
- description
- 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.
- interventionNames
- Drug: Tirzepatide
Primary outcomes (1)
- measure
- Pathologic Response at 6 months from Cycle 1 Day 1
- timeFrame
- At the end Cycle 6 Day 28 (Approximately 6 months from Cycle 1 Day 1with each cycle approximately 28 days)
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion 1. Age ≥ 18 years 2. Histologically confirmed endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid EC 3. BMI ≥ 30 kg/m2 4. 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 5. 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 6. For participants with EIN: no evidence of extrauterine disease based on clinically appropriate evaluation 7. Ability to provide informed consent and comply with study procedures and follow-up Exclusion 1. Mismatch repair-deficient (MMRd) tumors 2. p53-abnormal tumors 3. Known hypersensitivity or contraindication to either: 1. Tirzepatide, or 2. LNG-IUD 4. Prior LNG-IUD in place at the time of EIN or endometrial cancer diagnosis 5. Current systemic progestin therapy 6. 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 7. Type 1 diabetes or a history of pancreatitis, medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) 8. Pregnancy, breastfeeding, or intention to become pregnant during the study treatment 9. Concurrent malignancy requiring active treatment (except non-melanoma skin cancer) 10. Any medical, psychiatric, or social condition, that in the opinion of the investigator, would interfere with study participation or safety 11. Participants with diabetic eye disease, including non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema 12. Severe renal impairment, defined as eGFR \< 30 mL/min/1.73m2
References
Publications (0)
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