Endometrial Atypical HyperplasiaPhase 2SWIFTNCT07820358
Semaglutide, Weight Loss, and LNG-IUD for Conservative Treatment of Endometrial Atypical Hyperplasia and Grade 1 Endometrial Cancer
A Phase 2 study testing Semaglutide (Wegovy) weekly injection, LNG-IUD (Progestin) and Structured Weight Loss Program in people with Endometrial Atypical Hyperplasia and Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia, run by The Methodist Hospital Research Institute at 4 sites in United States.
Trial summary
The goal of this clinical trial is to learn if a combination treatment of a hormonal intrauterine device (LNG-IUD), semaglutide, and a structured weight loss program can treat endometrial atypical hyperplasia or grade 1 endometrioid endometrial cancer while preserving fertility in women of reproductive age with… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Atypical Hyperplasia, Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia, Endometrial Cancer Stage I
- What is being tested?
- Semaglutide (Wegovy) weekly injection, LNG-IUD (Progestin) and Structured Weight Loss Program
- Type of treatment
- Injection or infusion, Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Jan 2027to 31 Dec 2031
- Phase
- Phase 2
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
- Histological Diagnosis: Histologically confirmed endometrial atypical hyperplasia or FIGO grade 1 endometrioid Endometrial Cancer
- Imaging eligibility (for patients with endometrial cancer):
- Depth of myometrial invasion <50% confirmed by MRI or disease limited to the endometrium
- No evidence of extrauterine or metastatic disease on imaging.
- Treatment Rationale (at least one of the following must apply):
- Desire for future fertility: Patient expresses a documented desire to preserve the uterus and future reproductive function, with explicit acknowledgment that fertility-sparing treatment is not standard of care for endometrial cancer.
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- Medical inoperability: patients are considered a poor surgical candidate due to:
- Class III obesity (BMI ≥40 kg/m²); or ii. ASA Physical Status Classification score ≥3.
- Metabolic Profile: BMI ≥ 30 kg/m², or BMI 27-29.9 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea, or non-alcoholic fatty liver disease).
- Progestin washout: patients with prior progestin exposure are eligible provided the following minimum washout periods have been observed.
- Oral progestins: 7 days
- Injectable, short acting: 14 days
- Injectable, long acting: 6 months
- Contraceptive implant: 28 days
- LNG-IUD: 7 days after removal
Who cannot join
- Age ≥18 years
- Negative pregnancy test at screening
- Ability to provide written informed consent and comply with study procedures
- Willingness to undergo genetic counseling and MMR/IHC tumor profiling
- Willingness and ability to participate in a structured weight loss program, including attendance at counseling sessions (in person or virtual) and adherence to dietary and physical activity goals.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites
Houston Methodist at The Medical Center
Houston, Texas, 77030
Jaya S. Kamath, MS, 713-441-6616, jskamath@houstonmethodist.org
Houston Methodist Sugar Land
Houston, Texas, 77030
Jaya S. Kamath, MS, 713-441-6616, jskamath@houstonmethodist.org
Houston Methodist Willowbrook
Houston, Texas, 77030
Jaya S. Kamath, MS, 713-441-6616, jskamath@houstonmethodist.org
Houston Methodist Woodlands
Houston, Texas, 77030
Jaya S. Kamath, MS, 713-441-6616, jskamath@houstonmethodist.org
About this study
Official title: Semaglutide, Weight Loss, And Intrauterine Therapy For Fertility-Sparing And Conservative Treatment For Endometrial Atypical Hyperplasia And Early-Stage, Grade 1 Endometrioid Endometrial Cancer
The goal of this clinical trial is to learn if a combination treatment of a hormonal intrauterine device (LNG-IUD), semaglutide, and a structured weight loss program can treat endometrial atypical hyperplasia or grade 1 endometrioid endometrial cancer while preserving fertility in women of reproductive age with endometrial atypical hyperplasia (EAH) or FIGO grade 1 endometrioid endometrial cancer who wish to preserve their fertility. The main questions it aims to answer are:
- What proportion of participants achieve a complete pathological response after treatment?
- How durable is the response at 12 months?
- What effect does the treatment have on metabolic outcomes (weight, BMI, HbA1c) and quality of life?
Read more
Participants will:
- Receive an LNG-IUD
- Receive semaglutide 2.4mg
- Participate in a structured weight loss program
- Undergo hysteroscopy with endometrial sampling to assess treatment response
- Complete quality-of-life assessments at baseline, 6 months, and 12 months
- Conditions
- Endometrial Atypical Hyperplasia, Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia, Endometrial Cancer Stage I, Endometrial Cancer, Fertility-Sparing Treatment (FST), Obesity & Overweight
- Being tested
- Semaglutide (Wegovy) weekly injection, LNG-IUD (Progestin), Structured Weight Loss Program
- Keywords
- Endometrial atypical hyperplasia, Endometrial cancer, Endometrial cancer stage I, Endometrioid intraepithelial neoplasia, Fertility-sparing treatment, Obesity, Weight reduction, Semaglutide
- Medical subject headings
- Endometrial Hyperplasia, Endometrial Neoplasms, Obesity, Overweight, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide (Wegovy) weekly injectionDrug
Semaglutide 2.4 mg administered subcutaneously once weekly, following standard dose-escalation protocol, for the duration of the 6-month active treatment period. Used off-label in this trial for its metabolic effects in combination with LNG-IUD, rather than as monotherapy for weight loss.
LNG-IUD (Progestin)Device
Levonorgestrel-releasing intrauterine device inserted at study baseline and maintained through the active treatment and follow-up periods, providing continuous local progestin delivery to the endometrium in combination with systemic semaglutide.
Structured Weight Loss ProgramBehavioural
A structured, protocol-defined weight loss program combining dietary counseling and physical activity guidance, delivered concurrently with pharmacologic and device-based treatment to support metabolic response, distinct from weight loss achieved through semaglutide alone.
| Study group | Role | What they receive |
|---|---|---|
| Combination Fertility-Sparing Treatment | Experimental | Participants will receive a three-component combination intervention consisting of: (1) a levonorgestrel-releasing intrauterine device (LNG-IUD), inserted at baseline; (2) semaglutide 2.4 mg, administered per standard dosing schedule; and (3) a structured weight loss program. Participants will undergo hysteroscopy with endometrial sampling to assess pathological response. Treatment will be administered for 6 months of active intervention, followed by a 6-month follow-up period. Receives: Drug: Semaglutide (Wegovy) weekly injection; Device: LNG-IUD (Progestin); Behavioral: Structured Weight Loss Program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Response Rate
Pathological Response Rate (PRR) defined as the rate of regression of atypical hyperplasia or carcinoma on histopathological examination of the 6-month (end-of-treatment) hysteroscopic sample
Measured: 6 months
Secondary outcomes (5)
Time to response
Time to response in months from treatment initiation to first documented histopathological regression
Measured: 12 months
Adverse events
Incidence and severity of adverse events, graded per NCI-CTCAE v5.0, including drug-related (semaglutide) and device-related (LNG-IUD) events
Measured: 12 months
Durable response rate
The proportion of participants who achieve a complete pathological response and maintain that response, without evidence of disease recurrence or progression, through 12 months following treatment initiation. Durable response will be assessed via hysteroscopy with endometrial sampling.
Measured: 12 months
Disease progression rate
The proportion of participants who experience disease progression, defined as an increase in histologic grade or stage of endometrial atypical hyperplasia or endometrial cancer, without ever achieving a complete pathological response, assessed through 12 months from treatment initiation. Disease status will be assessed via hysteroscopy with endometrial sampling.
Measured: 12 months
Recurrence rate
The proportion of participants who experience recurrence of endometrial atypical hyperplasia or endometrial cancer following an initial complete pathological response, assessed through 12 months from treatment initiation. Disease status will be assessed via hysteroscopy with endometrial sampling.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2026
- Study start1 Jan 2027 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Endometrial Atypical HyperplasiaStudies of the same condition, open and under way.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A Bayesian adaptive design with early futility monitoring will guide accrual. The pilot phase will recruit 20 patients. If at least 11 patients achieve a pathological complete response, the study will continue to the expansion phase. In the expansion phase, a stopping rule will be applied such that if the posterior probability Pr(RR ≥ 70% \| data) falls below 0.05, the study will be terminated.
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aparna A. Kamat, The Methodist Hospital Research Institute
- Investigators
- Aparna A. Kamat, MD, Principal investigator, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07820358
- Sponsor's protocol ID
- PRO00043004
- Acronym
- SWIFT
- Status last verified
- Sep 2026
- First submitted
- 9 Sep 2026
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified individual participant data, including the study protocol and statistical analysis plan, will be made available to researchers who provide a methodologically sound proposal, beginning 12 months after publication of the primary results and ending 36 months after publication. Data will be shared for the purpose of achieving the aims outlined in the approved proposal, following execution of a data access agreement.
Publications
Podder V, Coleman RL, Hagemann AR, Singhania P, Powell MA, Herzog TJ, Slomovitz BM. Repositioning GLP-1 Receptor Agonists in Endometrial Cancer: Molecular Rationale, Preclinical Insights, and Translational Opportunities. Clin Cancer Res. 2026 Feb 4;32(3):447-454. doi: 10.1158/1078-0432.CCR-25-2819.
PubMed 41329840Peevey JF, Seagle BL, Maniar KP, Kim JJ. Association of body mass index with ER, PR and 14-3-3sigma expression in tumor and stroma of type I and type II endometrial carcinoma. Oncotarget. 2017 Jun 27;8(26):42548-42559. doi: 10.18632/oncotarget.17209.
PubMed 28476021Zhang Z, Dong L, Sui L, Yang Y, Liu X, Yu Y, Zhu Y, Feng Y. Metformin reverses progestin resistance in endometrial cancer cells by downregulating GloI expression. Int J Gynecol Cancer. 2011 Feb;21(2):213-21. doi: 10.1097/IGC.0b013e318207dac7.
PubMed 21270604Burzawa JK, Schmeler KM, Soliman PT, Meyer LA, Bevers MW, Pustilnik TL, Anderson ML, Ramondetta LM, Tortolero-Luna G, Urbauer DL, Chang S, Gershenson DM, Brown J, Lu KH. Prospective evaluation of insulin resistance among endometrial cancer patients. Am J Obstet Gynecol. 2011 Apr;204(4):355.e1-7. doi: 10.1016/j.ajog.2010.11.033. Epub 2011 Feb 16.
PubMed 21324431Zhu XX, Feng ZH, Liu LZ, Zhang Y. Liraglutide suppresses the proliferation of endometrial cancer cells through the adenosine 5'-monophosphate (AMP)-activated protein kinase signaling pathway. Chin Med J (Engl). 2021 Jan 19;134(5):576-578. doi: 10.1097/CM9.0000000000001363. No abstract available.
PubMed 33470656Dai H, Li Y, Lee YA, Lu Y, George TJ, Donahoo WT, Lee KP, Nakshatri H, Allen J, Guo Y, Sun RC, Guo J, Bian J. GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity. JAMA Oncol. 2025 Oct 1;11(10):1186-1193. doi: 10.1001/jamaoncol.2025.2681.
PubMed 40839273Wang L, Xu R, Kaelber DC, Berger NA. Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes. JAMA Netw Open. 2024 Jul 1;7(7):e2421305. doi: 10.1001/jamanetworkopen.2024.21305.
PubMed 38967919Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
PubMed 33567185Wichmann IA, Cuello MA. Obesity and gynecological cancers: A toxic relationship. Int J Gynaecol Obstet. 2021 Oct;155 Suppl 1(Suppl 1):123-134. doi: 10.1002/ijgo.13870.
PubMed 34669205Kailasam A, Cucinella G, Fought AJ, Cliby W, Mariani A, Glaser G, Langstraat C. Nonsurgical management of early-stage endometrial cancer due to obesity: a survey of the practice patterns of current Society of Gynecologic Oncology members. Gynecol Oncol Rep. 2023 Oct 4;50:101280. doi: 10.1016/j.gore.2023.101280. eCollection 2023 Dec.
PubMed 37927533Kong W, Deng B, Shen X, John C, Haag J, Sinha N, Lee D, Sun W, Chen S, Zhang H, Clontz A, Hursting SD, Zhou C, Bae-Jump V. Tirzepatide as an innovative treatment strategy in a pre-clinical model of obesity-driven endometrial cancer. Gynecol Oncol. 2024 Dec;191:116-123. doi: 10.1016/j.ygyno.2024.10.004. Epub 2024 Oct 10.
PubMed 39388742Westin SN, Fellman B, Sun CC, Broaddus RR, Woodall ML, Pal N, Urbauer DL, Ramondetta LM, Schmeler KM, Soliman PT, Fleming ND, Burzawa JK, Nick AM, Milbourne AM, Yuan Y, Lu KH, Bodurka DC, Coleman RL, Yates MS. Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer. Am J Obstet Gynecol. 2021 Feb;224(2):191.e1-191.e15. doi: 10.1016/j.ajog.2020.08.032. Epub 2020 Aug 15.
PubMed 32805208Janda M, Robledo KP, Gebski V, Armes JE, Alizart M, Cummings M, Chen C, Leung Y, Sykes P, McNally O, Oehler MK, Walker G, Garrett A, Tang A, Land R, Nicklin JL, Chetty N, Perrin LC, Hoet G, Sowden K, Eva L, Tristram A, Obermair A. Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial. Gynecol Oncol. 2021 Apr;161(1):143-151. doi: 10.1016/j.ygyno.2021.01.029.
PubMed 33762086