Grade 1 Endometrial Endometrioid CarcinomaEarly Phase 1TIDENCT07812636
Tirzepatide and Levonorgestrel IUD Therapy for EIN and Early-Stage Endometrial Cancer
A Early Phase 1 study testing Tirzepatide in people with Grade 1 Endometrial Endometrioid Carcinoma and Endometrial Intraepithelial Neoplasia, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Grade 1 Endometrial Endometrioid Carcinoma, Endometrial Intraepithelial Neoplasia, Metabolic Comorbidities
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to 1 Aug 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
Shaina Bruce, 717-531-8144, sbruce2@pennstatehealth.psu.edu
Xin Liu, 717-531-3073, xliu2@pennstatehealth.psu.edu
About this study
Official title: Combination Tirzepatide and Levonorgestrel Intrauterine Device Therapy for Endometrial Intraepithelial Neoplasia (EIN) and Grade 1 Endometrioid Endometrial Carcinoma: A Pilot Window-of-Opportunity Study
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.
Read the detailed description
Endometrial cancer is one of the most common gynecologic malignancies in the United States, with an increasing incidence rate. Obesity has been identified as a major risk factor for endometrial carcinogenesis and is prevalent among patients with endometrial intraepithelial neoplasia (EIN) and early-stage endometrial cancer. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1 RA), can cause meaningful weight loss and improvement in metabolic parameters. Levonorgestrel intrauterine device (LNG-IUD) therapy is a standard hormonal treatment for local EIN and grade 1 endometrioid endometrial carcinoma. This single-arm, single-center investigator-initiated study will evaluate the feasibility, safety, and preliminary efficacy of combining tirzepatide with standard LNG-IUD treatment in patients with EIN or grade 1 endometrioid endometrial carcinoma with co-existing obesity and metabolic risk factors. Eligible participants will be enrolled after initial histological confirmation of either EIN or grade 1 endometrioid endometrial carcinoma. Clinical management will remain at the discretion of the treating physician.
- Conditions
- Grade 1 Endometrial Endometrioid Carcinoma, Endometrial Intraepithelial Neoplasia, Metabolic Comorbidities
- Being tested
- Tirzepatide
- Keywords
- Tirzepatide, LNG-IUD
- Medical subject headings
- Endometrial Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tirzepatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Hemoglobin A1c and Lipid Profile
Measured: 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
Assess the incidence and severity of adverse events during study treatment, including adverse events considered related to tirzepatide or LNG-IUD therapy, graded according to CTCAE version 5.0 where applicable.
Measured: 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
Quality of life will be assessed using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). This survey form is a questionnaire, and participants will answer 3-point and 5-point Likert Scale questions as well as yes or no questions. This survey does not provide an aggregated score as it is opinion based. If the survey shows that a patient's quality of life is being impacted due to study treatment, appropriate action will be taken at the discretion of the treating physician.
Measured: Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28
Change in Weight
Participants weight will be collected for approximately 6 months to assess change in weight while using Tirzepatide.
Measured: 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
Participants BMI will be collected for approximately 6 months to assess changes in BMI while utilizing Tirzepatide
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 May 2028 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Grade 1 Endometrial Endometrioid CarcinomaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shaina Bruce, Milton S. Hershey Medical Center
- Investigators
- Shaina Bruce, MD, Principal investigator, Penn State Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07812636
- Sponsor's protocol ID
- PSCI-26-029
- Acronym
- TIDE
- Status last verified
- Sep 2026
- First submitted
- 26 Aug 2026
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Tirzepatide and Levonorgestrel Intrauterine Device Therapy for Endometrial Intraepithelial Neoplasia (EIN) and Grade 1 Endometrioid Endometrial Carcinoma: A Pilot Window-of-Opportunity Study
- ClinicalTrials.gov ID
- NCT07812636
- Acronym / sponsor ID
- TIDE / PSCI-26-029
- Conditions
- Grade 1 Endometrial Endometrioid Carcinoma, Endometrial Intraepithelial Neoplasia, Metabolic Comorbidities
- Keywords
- Tirzepatide, LNG-IUD
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 1 May 2028 (estimated)
- Study completion
- 1 Aug 2028 (estimated)
- First posted
- 10 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Endometrial cancer is one of the most common gynecologic malignancies in the United States, with an increasing incidence rate. Obesity has been identified as a major risk factor for endometrial carcinogenesis and is prevalent among patients with endometrial intraepithelial neoplasia (EIN) and early-stage endometrial cancer. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1 RA), can cause meaningful weight loss and improvement in metabolic parameters. Levonorgestrel intrauterine device (LNG-IUD) therapy is a standard hormonal treatment for local EIN and grade 1 endometrioid endometrial carcinoma. This single-arm, single-center investigator-initiated study will evaluate the feasibility, safety, and preliminary efficacy of combining tirzepatide with standard LNG-IUD treatment in patients with EIN or grade 1 endometrioid endometrial carcinoma with co-existing obesity and metabolic risk factors. Eligible participants will be enrolled after initial histological confirmation of either EIN or grade 1 endometrioid endometrial carcinoma. Clinical management will remain at the discretion of the treating physician.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| LNG-IUD and Tirzepatide Management | Experimental | Drug: TirzepatideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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
Key exclusion criteria (14 listed)
- Mismatch repair-deficient (MMRd) tumors
- p53-abnormal tumors
- Known hypersensitivity or contraindication to either:
- Prior LNG-IUD in place at the time of EIN or endometrial cancer diagnosis
- Current systemic progestin therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideTirzepatide 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. | Drug | LNG-IUD and Tirzepatide Management |
Primary outcome
Pathologic Response at 6 months from Cycle 1 Day 1
Time frame: At the end Cycle 6 Day 28 (Approximately 6 months from Cycle 1 Day 1with each cycle approximately 28 days)
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.
5 secondary outcomes
Change in metabolic parameters
Time frame: 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
Time frame: 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
Time frame: Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 28, and 3 months from Cycle 6 Day 28
Change in Weight
Time frame: 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
Time frame: 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Shaina Bruce, MD principal investigator
Penn State Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tirzepatide in people with Grade 1 Endometrial Endometrioid Carcinoma and Endometrial Intraepithelial Neoplasia, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Crystal Sowers (7175315471, PSCI-CTO@pennstatehealth.psu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Response at 6 months from Cycle 1 Day 1 (time frame: At the end Cycle 6 Day 28 (Approximately 6 months from Cycle 1 Day 1with each cycle approximately 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.