Semaglutide, Weight Loss, and LNG-IUD for Conservative Treatment of Endometrial Atypical Hyperplasia and Grade 1 Endometrial Cancer (SWIFT)
2026年9月9日 更新者：Aparna A. Kamat、The Methodist Hospital Research Institute
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?
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
研究概览
地位
尚未招聘
研究类型
介入性
注册 (估计的)
48
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
Texas
-
Houston、Texas、美国、77030
- Houston Methodist at The Medical Center
-
接触：
- Jaya S. Kamath, MS
- 电话号码：713-441-6616
- 邮箱：jskamath@houstonmethodist.org
-
Houston、Texas、美国、77030
- Houston Methodist Sugar Land
-
接触：
- Jaya S. Kamath, MS
- 电话号码：713-441-6616
- 邮箱：jskamath@houstonmethodist.org
-
Houston、Texas、美国、77030
- Houston Methodist Willowbrook
-
接触：
- Jaya S. Kamath, MS
- 电话号码：713-441-6616
- 邮箱：jskamath@houstonmethodist.org
-
Houston、Texas、美国、77030
- Houston Methodist Woodlands
-
接触：
- Jaya S. Kamath, MS
- 电话号码：713-441-6616
- 邮箱：jskamath@houstonmethodist.org
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria:
- 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.
- Medical inoperability: patients are considered a poor surgical candidate due to:
i. 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
Exclusion Criteria:
- 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.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Combination Fertility-Sparing Treatment
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.
|
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.
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.
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.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Pathological Response Rate
大体时间：6 months
|
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
|
6 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Time to response
大体时间：12 months
|
Time to response in months from treatment initiation to first documented histopathological regression
|
12 months
|
|
Adverse events
大体时间：12 months
|
Incidence and severity of adverse events, graded per NCI-CTCAE v5.0, including drug-related (semaglutide) and device-related (LNG-IUD) events
|
12 months
|
|
Durable response rate
大体时间：12 months
|
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.
|
12 months
|
|
Disease progression rate
大体时间：12 months
|
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.
|
12 months
|
|
Recurrence rate
大体时间：12 months
|
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.
|
12 months
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Body weight change
大体时间：12 months
|
Change in body weight, measured in kilograms, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
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Body mass index (BMI) change
大体时间：12 months
|
Change in body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
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Waist circumference change
大体时间：12 months
|
Change in waist circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
|
Hip circumference change
大体时间：12 months
|
Change in hip circumference, measured in centimeters, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
|
Waist-to-hip ratio change
大体时间：12 months
|
Change in waist-to-hip ratio, calculated as waist circumference divided by hip circumference, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
|
Glycated Hemoglobin change
大体时间：12 months
|
Change in glycated hemoglobin (HbA1c), measured as a percentage, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
|
Weight-Related Quality of Life (WRQOL)
大体时间：12 months
|
Change in weight-related quality of life, assessed using a validated WRQOL questionnaire, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
|
Health-Related Quality of Life (HRQOL)
大体时间：12 months
|
Change in health-related quality of life, assessed using a validated HRQOL questionnaire, from baseline to 6 and 12 months following treatment initiation.
|
12 months
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Aparna A. Kamat, MD、The Methodist Hospital Research Institute
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Wilding 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.
- Wang 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.
- Dai 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.
- 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.
- Peevey 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.
- Zhang 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.
- Burzawa 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.
- Zhu 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.
- Wichmann 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.
- Kailasam 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.
- Kong 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.
- Westin 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.
- Janda 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.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2027年1月1日
初级完成 (估计的)
2028年12月31日
研究完成 (估计的)
2031年12月31日
研究注册日期
首次提交
2026年9月9日
首先提交符合 QC 标准的
2026年9月9日
首次发布 (实际的)
2026年9月15日
研究记录更新
最后更新发布 (实际的)
2026年9月15日
上次提交的符合 QC 标准的更新
2026年9月9日
最后验证
2026年8月1日
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- PRO00043004
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
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.
IPD 共享时间框架
Data will become available beginning 12 months after publication of the primary study results and will remain available for 36 months thereafter.
IPD 共享访问标准
De-identified individual participant data, including the study protocol, statistical analysis plan, and informed consent form, will be available to researchers who provide a scientifically sound proposal for data use.
Requests should be directed to the principal investigator.
Proposals will be reviewed to confirm that the intended use is consistent with the original trial objectives and applicable data protection regulations.
Approved requesters will be required to sign a data access agreement prior to receiving data.
Access will be granted for the purpose of achieving the aims outlined in the approved proposal.
IPD 共享支持信息类型
- 研究方案
- 树液
- 国际碳纤维联合会
- 企业社会责任
药物和器械信息、研究文件
研究美国 FDA 监管的药品
是的
研究美国 FDA 监管的设备产品
是的
在美国制造并从美国出口的产品
不
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