GLP-1 Peptide Atlas, by Delfa

Not yet recruitingPhase 2

A Study of Weight Loss Intervention With Tirzepatide and Progestin Intrauterine Device to Treat Endometrial Hyperplasia and Grade 1 Endometrial Cancer

Tirzepatide With Progestin Intrauterine Device to Treat Endometrial Hyperplasia and Grade 1 Endometrial Cancer in Overweight and Obese Women

Lead sponsor

National Cancer Institute (NCI)

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

Recruiting sites

—

Enrollment

estimated

Study population

Obesity / overweight, Oncology

Key I/E criteria

•BMI ≥27•Female

Primary endpoint

•Weighted pathological complete response (pCR)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07349641

Org study IDNCI-2026-00081

Secondary IDMDA24-19-01M D Anderson Cancer Center

Secondary IDP30CA016672

Secondary IDUG1CA242609

Timeline

Milestones

Study first posted2026-01-20actual

Last update posted2026-05-14actual

Study start2026-07-06estimated

Primary completion2028-12-31estimated

Study completion2029-12-31estimated

Assets

Investigational agents

Tirzepatide

Study populations

Who this study enrolls

Obesity / overweightOncology

Eligibility

Who can enroll

Minimum age18 Years

SexFemale

Healthy volunteersNot accepted

Inclusion criteria

•Women who have a pathologic diagnosis of AH/EIN or grade 1 endometrioid endometrial cancer confirmed on dilation and curettage (D\&C) and desire non-surgical management, who are overweight (body mass index [BMI] ≥ 27 kg/m^2) with a weight-related comorbidity (hypertension, type 2 diabetes, or high cholesterol) or obese (BMI ≥ 30 kg/m^2) with or without weight-related comorbidities

•Prior progesterone treatment for conditions other than AH/EIN or endometrial cancer is allowed, but a 28-day washout period is required before levonorgestrel IUD placement. If archival tissue is available from prior to any progesterone treatment but after the diagnosis of AH/EIN/EC, the washout period is not needed

•Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of tirzepatide in participants < 18 years of age, children and adolescents < 18 years of age are excluded from this study but will be eligible for future pediatric trials, if applicable

•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)

•Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

•For participants with a history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

•Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load

•Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible

•Ability to comply with EMB every 3 months

•Women currently using oral hypoglycemic agents (e.g., metformin) are eligible for the study

•Ability to understand and the willingness to sign a written informed consent document in English or Spanish

Exclusion criteria

•Women with grade 2-3 endometrioid, or women with serous, clear cell, mucinous, squamous, transitional cell, sarcomas, or carcinosarcoma histology

•Evidence of extrauterine spread of disease on imaging or during surgical evaluation

•Participants may not be receiving any other investigational agents or anticancer therapies (including chemotherapy, radiation therapy, hormonal, or antibody-based therapy). Prior treatment should have a minimum washout period of 14 days

•History of allergic reactions attributed to compounds of similar chemical or biologic composition to the levonorgestrel IUD or any GLP-1 agonist

•Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements

•Pregnant women are excluded from this study. Because of this, a pregnancy test is part of the screening for the study and women who are pregnant or planning pregnancy within 6 months after the end of the study will be excluded. The LNG-IUD is an Food and Drug Administration (FDA)-approved contraceptive agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.

Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with tirzepatide, breastfeeding should be discontinued if the mother is treated with tirzepatide

•Women who have any severe and/or uncontrolled medical conditions such as:

–Unstable angina pectoris, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease,

–Symptomatic congestive heart failure of New York Heart Association class III or IV,

–Active (acute or chronic) or uncontrolled severe infection (not responding to antibiotics), liver diseases such as cirrhosis and decompensated liver disease,

–Known severely impaired lung function (spirometry and diffusion capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air), or

–Active, bleeding diathesis

•Other malignancies within the past 3 years except for basal or squamous cell carcinoma of the skin

•Active (acute or chronic) or uncontrolled severe infections (not responding to antibiotics), including acute pelvic inflammatory disease

•Congenital or acquired uterine anomaly which distorts the uterine cavity

•Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use one additional highly effective method of contraception in addition to the LNG-IUD during the study and 8 weeks after. Acceptable highly effective contraception methods include a combination of any of the following:

–Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;

–Total abstinence or;

–Male sterilization;

–Female bilateral tubal ligation or bilateral salpingectomy Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy or tubal ligation at least six weeks prior to study initiation. When the diagnosis of menopause is unclear based on patient history, we will assess follicle-stimulating hormone \\ (FSH) levels for confirmation. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential

•Tirzepatide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia (MEN) 2A or 2B. Such women will be excluded

•Participants taking any other prescription medication intended to induce weight loss (i.e., orlistat, phentermine-topiramate, naltrexone-bupropion). A 28-day washout period is required if such women want to enter the study

•Participants on active intermittent fasting

•Participants currently using insulin for glucose control

•Participants who have previously used any glucagon-like peptide (GLP) medications (liraglutide, semaglutide, dulaglutide, exenatide), whether oral or injectable

•Participants diagnosed with Lynch Syndrome

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Other clinical outcomes

Glycemic / diabetes

Weight & body composition

Cardiometabolic biomarkers

Weight & body composition

1 endpoint

Secondary/protocol endpoint

Percent weight change

Time frame:Every 4 weeks up to week 20 and at weeks 26, 39, and 52

Body weight, % change

percent change from baseline, improvement

Glycemic / diabetes

2 endpoints

Secondary/protocol endpoint

Percent change in hemoglobin A1C

Time frame:At baseline and weeks 12, 26, 39, and 52

HbA1c, % change

percent change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percent change in fasting blood glucose

Time frame:Every 4 weeks up to week 20 and at weeks 26, 39, and 52

Fasting glucose, change

percent change from baseline, improvement

LOINC 1558-6

Cardiometabolic biomarkers

1 endpoint

Other/protocol endpoint/low confidence

Change in systemic inflammation and metabolic markers

Time frame:At baseline and 12, 26, 39 and 52 weeks

percent change from baseline, improvement

Other clinical outcomes

3 endpoints

Primary/protocol endpoint

Weighted pathological complete response (pCR)

Time frame:At 26 weeks

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Proportion of participants who achieve pCR on endometrial biopsy

Time frame:At 52 weeks

categorical status, improvement

Secondary/protocol endpoint/low confidence

Rate of hyperplasia persistence and progression to EC

Time frame:At 26 and 52 weeks

categorical status, event

Other (unclassified)

5 endpoints

Secondary/protocol endpoint/low confidence

Time to complete response and duration of response

Time frame:Up to 52 weeks

time to event, descriptive

Secondary/protocol endpoint/low confidence

Percent change in cell proliferation

Time frame:At baseline and 12, 26, 39, and 52 weeks

percent change from baseline, descriptive

Other/protocol endpoint/low confidence

Change in the endometrial immune microenvironment

Time frame:At baseline and 12, 26, 39, and 52 weeks

change from baseline, descriptive

Other/protocol endpoint/low confidence

Weight-independent effects of glucagon-like peptide 1 on cell proliferation (Ki-67+)

Time frame:At baseline and 12, 26, 39 and 52 weeks

descriptive

Other/protocol endpoint/low confidence

Effect of intervention on treatment response

Time frame:At 26 and 52 weeks

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.