Clinical trial
SHAPE-ENDO: Pilot Randomized Trial of Multimodal Pre-Surgical Optimization Versus Standard Surgery in Patients With Obesity and Early-Stage Endometrial Cancer
Opening soon · Phase 4 · 0 countries · Registry ID NCT07462663
What this study is about
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.
Basic eligibility
Full registry criteria
Treatments and study arms
GLP-1 Receptor Agonist
Weekly subcutaneous semaglutide/GLP-1 receptor agonist therapy administered according to approved labeling, clinical indication, patient tolerance, and endocrinology assessment, with standard dose escalation up to the tolerated therapeutic dose. The intervention is used for weight loss and metabolic optimization in participants with severe obesity. Dose, adherence, tolerability, and reasons for dose modification or discontinuation will be recorded prospectively.
Levonorgestrel IUD (Lng-IUD)
Local hormonal therapy using a 52-mg levonorgestrel-releasing intrauterine system placed at baseline or within 14 days after baseline, with ultrasound confirmation of correct placement. The LNG-IUD is used within the protocolized SHAPE-ENDO strategy according to clinical indication, approved labeling, current guidelines, and physician judgment, for local disease control in atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage, low-risk endometrioid endometrial cancer. Tolerability, continuation, adverse events, and local histological response will be recorded prospectively.
Oral Progestins
Systemic hormonal therapy prescribed according to clinical criteria to support local disease control in atypical endometrial hyperplasia or early-stage endometrioid carcinoma. Typical regimens include medroxyprogesterone acetate (400-600 mg/day) or megestrol acetate (160-320 mg/day). Therapy is initiated or escalated when indicated based on tumor burden or suboptimal response to LNG-IUD. Oral progestins may be used within the protocolized SHAPE-ENDO strategy according to clinical indication, approved labeling, current guidelines, and physician judgment. Use, dosing, tolerance, and outcomes will be recorded prospectively.
Dietetic-Nutritional intervention
Personalized hypocaloric diet plan supervised by the clinical nutrition team as part of standard obesity and metabolic management. The program includes caloric restriction based on basal metabolic requirements, with the option of very low-calorie diets (VLCD) for 4-6 weeks in selected cases. Follow-up occurs at regular outpatient visits with recording of weight, BMI, waist circumference, and adherence. This intervention is part of routine clinical care and not assigned experimentally; outcomes are recorded prospectively.
Structured Exercise and Prehabilitation Program
A structured physical exercise program designed to improve functional capacity, aerobic tolerance, and surgical fitness. Program includes supervised or semi-supervised weekly sessions combining aerobic and strength training, typically 3 sessions per week for 30-45 minutes, adapted to baseline performance. The intervention is part of routine clinical care for patients with obesity undergoing surgical preparation and is not assigned experimentally. Data on adherence, tolerance, and functional outcomes are collected prospectively
Endometrial Biopsy With or Without Hysteroscopy
Scheduled histological surveillance performed at baseline and at follow-up intervals (typically 14 and 28-54 weeks) to assess local tumor status, including complete response, stability, or progression. Procedures include outpatient endometrial biopsy with optional hysteroscopy based on clinical indication. These evaluations form part of standard clinical care in patients managed conservatively for atypical endometrial hyperplasia or early-stage endometrioid carcinoma and are not assigned experimentally. Data are recorded prospectively to assess disease evolution and surgical eligibility.
Radiologic Surveillance (MRI and Transvaginal Ultrasound)
Radiologic evaluation using pelvic MRI and transvaginal ultrasound performed as part of routine clinical care to assess uterine disease, myometrial invasion, adnexal status, and treatment response. Imaging is typically performed at baseline to confirm staging and during follow-up when clinically indicated. These imaging modalities are used per standard clinical guidelines and are not assigned experimentally; results are collected prospectively to evaluate disease stability and surgical planning.
Standar upfront Surgery
Standard surgical treatment according to the institutional protocol of Hospital Universitari de Bellvitge for atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage low-risk endometrioid endometrial cancer. Surgery will usually include hysterectomy with bilateral salpingo-oophorectomy, sentinel lymph node assessment when indicated and feasible, and a minimally invasive or robotic approach whenever technically possible according to clinical judgment. Surgical approach, operative time, estimated blood loss, conversion to laparotomy, transfusion, hospital stay, intraoperative complications, 30-day postoperative complications, readmission, and sentinel lymph node detection will be recorded.
Primary outcomes
Number of participants enrolled per month during the active recruitment period. This outcome will assess the feasibility of recruiting eligible participants with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or low-risk endometrioid endometrial cancer and BMI ≥40 kg/m² into a pilot randomized clinical trial.
Proportion of eligible participants who agree to participate in the trial and accept random assignment to either standard immediate surgery or the SHAPE-ENDO multimodal pre-surgical optimization strategy.
Proportion of randomized participants who complete the planned follow-up required for the main pilot analysis, including surgical treatment and 30-day postoperative assessment, or completion of the assigned intervention period when applicable.
Proportion of randomized participants who comply with the main procedures planned in their assigned arm. In the control arm, this includes undergoing standard immediate surgery and postoperative follow-up. In the SHAPE-ENDO arm, this includes adherence to the multimodal strategy, scheduled visits, oncologic surveillance, and planned reassessment.
Proportion of participants randomized to the SHAPE-ENDO arm who complete the planned multimodal pre-surgical optimization strategy until the week 28 reassessment and, when applicable, until week 54.
Proportion of participants randomized to the SHAPE-ENDO arm who undergo surgery after the pre-surgical optimization period without histological, radiological, or clinical evidence of tumor progression.
Frequency of serious adverse events, tumor progression during the optimization period, and reasons for discontinuation or withdrawal from the study. Adverse events will be recorded prospectively and classified according to CTCAE v5.0 when applicable. These events will be described overall and by randomized arm when applicable.
Study locations
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