SHAPE-ENDO

Not yet recruitingPhase 4

SHAPE-ENDO: Pilot Randomized Trial of Multimodal Pre-Surgical Optimization Versus Standard Surgery in Patients With Obesity and Early-Stage Endometrial Cancer

SHAPE-ENDO (Strategic Hormonal Approach & Prehabilitation in Endometrial Cancer): An Open-Label, Pilot Randomized Clinical Trial Comparing Standard Immediate Surgery Versus a Multimodal Metabolic Optimization and Prehabilitation Strategy Before Surgery in Patients With Atypical Endometrial Hyperplasia or Low-Risk Endometrioid Endometrial Cancer and BMI ≥40 kg/m²

Lead sponsor

Hospital Universitari de Bellvitge

Assets

GLP-1 / incretin class catch-all / Semaglutide

Listed sites

Recruiting sites

—

Enrollment

estimated

Study population

Obesity / overweight, Oncology

Key I/E criteria

•BMI ≥40•Female

Primary endpoint

•Predefined metabolic and clinical optimization criteria (Body weight, % change, BMI, change, Waist circumference, change, HbA1c, change)

Identifiers

Registered as

NCT IDNCT07462663

Org study IDSHAPE-ENDO

Timeline

Milestones

Study first posted2026-03-10actual

Last update posted2026-05-13actual

Study start2026-09estimated (month precision)

Primary completion2027-05estimated (month precision)

Study completion2028-09estimated (month precision)

Assets

Investigational agents

GLP-1 / incretin class catch-all Semaglutide

Study populations

Who this study enrolls

Obesity / overweightOncology

Eligibility

Who can enroll

Minimum age18 Years

SexFemale

Healthy volunteersNot accepted

Inclusion criteria

•Female participants ≥18 years old.

•Histologically confirmed atypical endometrial hyperplasia/endometrial intraepithelial neoplasia (AEH/EIN) or low-risk endometrioid endometrial carcinoma, grade 1 or 2.

•Disease apparently confined to the uterine corpus, assessed by expert transvaginal ultrasound and/or pelvic magnetic resonance imaging.

•Low- or intermediate-risk disease according to ESGO-ESTRO-ESP 2025 criteria, including presurgical stages IA1, IA2, or IB.

•Negative or focal lymphovascular space invasion, if available.

•Favorable molecular profile, if available, including POLE-mutated, p53 wild-type, MMR-deficient, or NSMP estrogen receptor-positive disease.

•Body mass index ≥40 kg/m² at inclusion.

•Considered a candidate for surgical treatment by the multidisciplinary tumor board.

•Ability to understand and sign written informed consent after receiving oral and written information about the study, including acceptance of random assignment to either standard immediate surgery or the SHAPE-ENDO multimodal pre-surgical optimization strategy.

Exclusion criteria

•FIGO stage IA3, IC, II, or higher disease.

•Extensive lymphovascular space invasion, if available.

•High-risk molecular profile, including p53-abnormal/mutated disease or NSMP estrogen receptor-negative disease.

•Non-endometrioid histology, including serous carcinoma, clear-cell carcinoma, carcinosarcoma, mixed histology, or other high-risk histological subtypes.

•Metastatic disease or suspicion of extrauterine disease.

•Considered medically inoperable or "unfit" for surgery because of severe comorbidity, frailty, anesthetic contraindication, or any other clinical reason contraindicating surgical treatment.

•Contraindication to GLP-1 receptor agonist therapy or progestin-based hormonal therapy, including levonorgestrel-releasing intrauterine device or oral progestins.

•Previous pancreatitis, medullary thyroid carcinoma, or multiple endocrine neoplasia type 2.

•Concurrent participation in another interventional pharmacological clinical trial.

•Any condition that, in the investigator's judgment, may compromise participant safety, interfere with protocol compliance, or make participation inappropriate.

Endpoints (20)

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 clinical outcomes

Cardiometabolic biomarkers

Glycemic / diabetes

Patient-reported / QoL

Cardiovascular outcomes

Weight & body composition

Safety / tolerability / PK

Cardiovascular outcomes

1 endpoint

Secondary/protocol endpoint

Overall Survival (OS)

Time frame:Up to 5 years after study inclusion.

All-cause death

time to event, event

SNOMED 419620001

Weight & body composition

1 endpoint

Secondary/protocol endpoint

Changes in anthropometric measures (BMI, waist circumference, visceral adiposity)

Time frame:Up to 12 months

change from baseline, improvement

componentsBMI, change, Waist circumference, change, Visceral fat, change, ≥5% weight-loss responders, ≥10% weight-loss responders, ≥15% weight-loss responders

Glycemic / diabetes

2 endpoints

Secondary/protocol endpoint

Change in Glycated Hemoglobin (HbA1c)

Time frame:Baseline to 6 months and Baseline to 12 months

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in Fasting Plasma Glucose

Time frame:Baseline to 6 months and Baseline to 12 months

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Cardiometabolic biomarkers

5 endpoints

Secondary/protocol endpoint

Change in Serum Triglycerides

Time frame:Baseline to 6 months and Baseline to 12 months

Triglycerides, change

change from baseline, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in HDL Cholesterol

Time frame:Baseline to 6 months and Baseline to 12 months

HDL-C, change

change from baseline, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in LDL Cholesterol

Time frame:Baseline to 6 months and Baseline to 12 months

LDL-C, change

change from baseline, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in Blood Pressure

Time frame:Baseline to 6 months and Baseline to 12 months

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in C-Reactive Protein (CRP)

Time frame:Baseline to 6 months and Baseline to 12 months

change from baseline, improvement

Patient-reported / QoL

2 endpoints

Secondary/protocol endpoint

Change in Health-Related Quality of Life Score (SF-36)

Time frame:Baseline to 12 months

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

Change in Quality of Life Score (EORTC QLQ-C30)

Time frame:Baseline to 12 months

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Incidence of adverse events related to standard-of-care treatments

Time frame:Baseline to 12 months

Treatment-emergent AEs (any)

event count, event

Other clinical outcomes

8 endpoints

Primary/protocol endpoint/low confidence

Proportion of patients achieving predefined metabolic and clinical optimization criteria

Time frame:Up to 12 months

threshold achievement, improvement

componentsBody weight, % change, BMI, change, Waist circumference, change, HbA1c, change, Systolic BP, change, LDL-C, change

Secondary/protocol endpoint

Histological Complete Response Rate of Endometrial Lesion

Time frame:Baseline to 6 months and 12 months

categorical status, improvement

Secondary/protocol endpoint

Proportion of patients reaching eligibility for minimally invasive surgery

Time frame:Up to 12 months

threshold achievement, improvement

Secondary/protocol endpoint

Perioperative outcomes following minimally invasive surgery

Time frame:At time of surgery and 30 days postoperatively

descriptive

Secondary/protocol endpoint/low confidence

Adherence to GLP-1 therapy, hormonal therapy, diet, and exercise interventions

Time frame:Baseline to 12 months

descriptive

Secondary/protocol endpoint/low confidence

Change in Functional Capacity

Time frame:Baseline to 12 months

change from baseline, improvement

Secondary/protocol endpoint

Disease-Free Survival (DFS)

Time frame:Up to 5 years after inclusion or definitive treatment.

time to event, event

componentsAll-cause death

Secondary/protocol endpoint

Recurrence-Free Survival (RFS)

Time frame:Up to 5 years after inclusion or definitive treatment.

time to event, event

Publications (19)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Real-World Weight Loss Among Patients Initiating Semaglutide 2.4 mg and Enrolled in WeGoTogether, a Digital Self-Support Application.
Advances in therapy2025 Oct (month)PMID40768192doi:10.1007/s12325-025-03325-1via CT.gov background
Risk factors for postoperative complications following hysterectomy in endometrial cancer patients: A systematic review.
Journal of gynecology obstetrics and human reproduction2025 Sep (month)PMID40316173doi:10.1016/j.jogoh.2025.102964via CT.gov background
ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025.
The Lancet. Oncology2025 Aug (month)PMID40744042doi:10.1016/S1470-2045(25)00167-6via CT.gov background
The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists as a Type of Conservative Treatment of Endometrial Cancer in Women of Reproductive Age: A Review of the Literature and a Call for Study.
Cureus2024 Sep (month)PMID39429275doi:10.7759/cureus.69678via CT.gov background
Comparative effects of progestin-based combination therapy for endometrial cancer or atypical endometrial hyperplasia: a systematic review and network meta-analysis.
Frontiers in oncology2024 (year)PMID38764577doi:10.3389/fonc.2024.1391546via CT.gov background
Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.
Nature medicine2022 Oct (month)PMID36216945doi:10.1038/s41591-022-02026-4via CT.gov background
Conservative management of patients with endometrial intraepithelial neoplasia (EIN): Factors that could affect response and pregnancy rates.
Turkish journal of medical sciences2022 Jun (month)PMID36326317doi:10.55730/1300-0144.5384via CT.gov background
Impact of Obesity on Sentinel Lymph Node Mapping in Patients with apparent Early-Stage Endometrial Cancer: The ObeLyX study.
Gynecologic oncology2022 May (month)PMID35314087doi:10.1016/j.ygyno.2022.03.003via CT.gov background
Lymphadenectomy, obesity and open surgery are associated with surgical complications in endometrial cancer.
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology2021 Nov (month)PMID34238643doi:10.1016/j.ejso.2021.06.034via CT.gov background
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.
JAMA2021 Apr 13PMID33755728doi:10.1001/jama.2021.3224via CT.gov background
Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.
Lancet (London, England)2021 Mar 13PMID33667417doi:10.1016/S0140-6736(21)00213-0via CT.gov background
ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society2021 Jan (month)PMID33397713doi:10.1136/ijgc-2020-002230via CT.gov background
Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery: A Randomized Clinical Trial.
JAMA surgery2018 Dec 1PMID30193337doi:10.1001/jamasurg.2018.1645via CT.gov background
Fertility-Preserving Treatment in Young Women With Grade 1 Presumed Stage IA Endometrial Adenocarcinoma: A Meta-Analysis.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society2018 Feb (month)PMID29266019doi:10.1097/IGC.0000000000001164via CT.gov background
Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia<sup/>.
Journal of women's health (2002)2017 Apr (month)PMID27901412doi:10.1089/jwh.2016.5774via CT.gov background
Long-Term Oncologic and Reproductive Outcomes in Young Women With Early Endometrial Cancer Conservatively Treated: A Prospective Study and Literature Update.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society2016 Nov (month)PMID27654262doi:10.1097/IGC.0000000000000825via CT.gov background
Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies.
Annals of oncology : official journal of the European Society for Medical Oncology2015 Aug (month)PMID25791635doi:10.1093/annonc/mdv142via CT.gov background
Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis.
American journal of obstetrics and gynecology2012 Oct (month)PMID23021687doi:10.1016/j.ajog.2012.08.011via CT.gov background
Treatment effects, disease recurrence, and survival in obese women with early endometrial carcinoma : a Gynecologic Oncology Group study.
Cancer2006 Dec 15PMID17096437doi:10.1002/cncr.22351via CT.gov background

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.