Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
SHAPE-ENDO is a single-center, open-label, pilot randomized clinical trial conducted at Hospital Universitari de Bellvitge in Barcelona, Spain. The study will evaluate the feasibility, safety, and acceptability of comparing two treatment strategies in women with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or low-risk endometrioid endometrial cancer and grade III obesity, defined as BMI ≥40 kg/m². Eligible participants will be randomized in a 1:1 ratio to one of two arms. The control arm will undergo standard immediate surgery according to the institutional clinical protocol. The experimental arm will receive the SHAPE-ENDO multimodal pre-surgical optimization strategy before surgery. The SHAPE-ENDO strategy includes metabolic treatment with semaglutide/Wegovy®, local hormonal therapy with a levonorgestrel-releasing intrauterine device/Mirena® with or without oral medroxyprogesterone acetate/Progevera®, a structured nutritional program, adapted physical exercise, and scheduled oncologic surveillance with clinical evaluation, imaging, and endometrial biopsy with or without hysteroscopy. The experimental strategy will initially last 28 weeks. In participants with clinical, metabolic, or anthropometric benefit, adequate tolerance, and no evidence of tumor progression, the strategy may be extended up to 54 weeks before surgery. The primary objective is to evaluate the feasibility, safety, and acceptability of the randomized trial design. Primary feasibility outcomes include recruitment rate, acceptance of randomization, retention, adherence to the assigned intervention, completion of the SHAPE-ENDO strategy, progression during the optimization period, and the proportion of participants in the experimental arm who reach surgery without tumor progression. Secondary outcomes include perioperative morbidity, histological response in the experimental arm, metabolic and anthropometric changes, quality of life, treatment adherence, safety and tolerability, and exploratory long-term oncologic outcomes including overall survival, recurrence-free survival, and cancer-specific survival.
Conditions
Conditions (9)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Atypical Endometrial Hyperplasia | Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia | ALIAS | 0.90 |
| Atypical Endometrial Hyperplasia and Endometrial Carcinoma Stage I | — | UNRESOLVED | — |
| BMI>40 | — | UNRESOLVED | — |
| Endometrial Cancer | Malignant Endometrial Neoplasm | CURATED_BROADER | 0.80 |
| Endometrial Cancer Stage I | Malignant Endometrial Neoplasm | CURATED_BROADER | 0.80 |
| Endometrial Intraepithelial Neoplasia | Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia | ALIAS | 0.90 |
| Obesity | — | UNRESOLVED |
Interventions
Interventions (8)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Dietetic-Nutritional intervention | Behavioral | — | UNRESOLVED |
| Endometrial Biopsy With or Without Hysteroscopy | Procedure | — | UNRESOLVED |
| GLP-1 Receptor Agonist | Drug | — | UNRESOLVED |
| Levonorgestrel IUD (Lng-IUD) | Device | — | UNRESOLVED |
| Oral Progestins | Drug | — | UNRESOLVED |
| Radiologic Surveillance (MRI and Transvaginal Ultrasound) | Procedure | — | UNRESOLVED |
| Standar upfront Surgery | Procedure | — | UNRESOLVED |
| Structured Exercise and Prehabilitation Program | Behavioral | — |
Design
Arms and outcomes
Arms (2)
- type
- ACTIVE_COMPARATOR
- label
- Arm A - Standard Immediate Surgery
- description
- Participants randomized to the control arm will undergo standard immediate surgical treatment according to the institutional protocol of Hospital Universitari de Bellvitge. Surgery will usually include hysterectomy with bilateral salpingo-oophorectomy, sentinel lymph node assessment when indicated and feasible, and minimally invasive or robotic approach whenever technically possible according to clinical judgment. Intervention: Procedure/Surgery - Standard Immediate Surgery Standard surgical management according to institutional practice for atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage low-risk endometrioid endometrial cancer. Perioperative outcomes, surgical approach, conversion to laparotomy, estimated blood loss, operative time, hospital stay, transfusion, sentinel lymph node detection, intraoperative complications, and 30-day postoperative complications graded according to Clavien-Dindo will be recorded.
- interventionNames
- Procedure: Standar upfront Surgery
- type
- EXPERIMENTAL
- label
- Arm B - Experimental: SHAPE-ENDO Multimodal Strategy Before Surgery
- description
- Participants randomized to the experimental arm will receive the SHAPE-ENDO multimodal pre-surgical optimization strategy before surgery. The strategy includes semaglutide/Wegovy®, levonorgestrel-releasing intrauterine device/Mirena® with or without oral medroxyprogesterone acetate/Progevera®, structured nutritional intervention, adapted physical exercise, and scheduled oncologic surveillance. The strategy will last 28 weeks initially and may be extended up to 54 weeks if there is clinical, metabolic, or anthropometric benefit, adequate tolerance, and no tumor progression. Intervention: Drug - Semaglutide / Wegovy® Weekly subcutaneous semaglutide administered according to approved labeling, clinical indication, tolerance, and endocrinology assessment, with standard dose escalation up to the tolerated therapeutic dose. Dose, adherence, tolerability, adverse events, and reasons for dose modification or discontinuation will be recorded. Intervention: Device - Levonorgestrel-Releasing I
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (19)
- BACKGROUNDConcin N, Matias-Guiu X, Cibula D, Colombo N, Creutzberg CL, Ledermann J, Mirza MR, Vergote I, Abu-Rustum NR, Bosse T, Chargari C, Espenel S, Fagotti A, Fotopoulou C, Gatius S, Gonzalez-Martin A, Lax S, Levy B, Lorusso D, Macchia G, Marth C, Morice P, Oaknin A, Raspollini MR, Schwameis R, Sehouli J, Sturdza A, Taylor A, Westermann A, Wimberger P, Planchamp F, Nout RA. ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025. Lancet Oncol. 2025 Aug;26(8):e423-e435. doi: 10.1016/S1470-2045(25)00167-6. PMID 40744042
- BACKGROUNDIavazzo C, Gkegkes ID. Conservative management of patients with endometrial intraepithelial neoplasia (EIN): Factors that could affect response and pregnancy rates. Turk J Med Sci. 2022 Jun;52(3):870. doi: 10.55730/1300-0144.5384. Epub 2022 Jun 16. No abstract available. PMID 36326317
- BACKGROUNDCui J, Zhao YC, She LZ, Wang TJ. Comparative effects of progestin-based combination therapy for endometrial cancer or atypical endometrial hyperplasia: a systematic review and network meta-analysis. Front Oncol. 2024 May 3;14:1391546. doi: 10.3389/fonc.2024.1391546. eCollection 2024. PMID 38764577
- BACKGROUNDLaurelli G, Falcone F, Gallo MS, Scala F, Losito S, Granata V, Cascella M, Greggi S. Long-Term Oncologic and Reproductive Outcomes in Young Women With Early Endometrial Cancer Conservatively Treated: A Prospective Study and Literature Update. Int J Gynecol Cancer. 2016 Nov;26(9):1650-1657. doi: 10.1097/IGC.0000000000000825. PMID 27654262
- BACKGROUNDFan Z, Li H, Hu R, Liu Y, Liu X, Gu L. Fertility-Preserving Treatment in Young Women With Grade 1 Presumed Stage IA Endometrial Adenocarcinoma: A Meta-Analysis. Int J Gynecol Cancer. 2018 Feb;28(2):385-393. doi: 10.1097/IGC.0000000000001164. PMID 29266019
- BACKGROUNDMarnach ML, Butler KA, Henry MR, Hutz CE, Langstraat CL, Lohse CM, Casey PM. Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia<sup/> J Womens Health (Larchmt). 2017 Apr;26(4):368-373. doi: 10.1089/jwh.2016.5774. Epub 2016 Nov 30.