SHAPE-ENDO: Multimodal Pre-Surgical Optimization in Patients With Obesity and Early-Stage Endometrial Cancer (Phase 1)

What this study is testing ClinicalTrials.gov NCT07462663 ↗

Description as written by the study sponsor.

SHAPE-ENDO is a prospective, single-center, low-intervention, non-randomized, single-arm clinical trial conducted at Hospital Universitari de Bellvitge (Barcelona, Spain). The study is designed to evaluate a protocolized multimodal pre-surgical optimization strategy in women with severe obesity (BMI ≥40 kg/m²) and atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage, low-risk endometrioid endometrial cancer. The strategy is intended for selected patients in whom immediate surgery may be associated with increased perioperative risk due to obesity and comorbidities. Participants will receive a structured multimodal optimization program aimed at improving metabolic and functional status while maintaining local oncologic control. The multimodal strategy includes authorized treatments used according to clinical indication, product labeling, current guidelines, and physician judgment: semaglutide/GLP-1 receptor agonist therapy for metabolic optimization, local hormonal treatment with a levonorgestrel-releasing intrauterine device with or without oral progestins, structured nutritional intervention, adapted physical exercise, and scheduled clinical, imaging, and histological surveillance. The primary objective is to estimate the proportion of participants who achieve predefined pre-surgical optimization criteria after the multimodal strategy, including clinically relevant weight loss and/or reduction to BMI \<40 kg/m², absence of tumor progression, and acceptable anesthetic/surgical risk. Secondary outcomes include histological response, metabolic and anthropometric changes, treatment adherence, safety, health-related quality of life, feasibility of subsequent surgery, perioperative outcomes, and exploratory long-term survival outcomes. Participants will be followed during a 28-54 week optimization period. Long-term follow-up will assess recurrence, survival, quality of life, and metabolic outcomes. Exploratory adjusted comparisons may be performed against a historical cohort of patients with similar baseline characteristics previously treated at the same institution.

Treatments tested

• GLP-1 Receptor Agonist also known as Semaglutide Drug

  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) also known as LNG-IUD Device

  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 also known as Medroxyprogesterone acetate, Megestrol acetate, Progestin therapy Drug

  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 also known as Hypocaloric diet program, Nutritional Counseling, Dietary Prehabiilitation Behavioral

  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 also known as Exercise Prehabilitation, Supervised Physical Activity Program, Combined Aerobic and Strength Training Behavioral

  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 also known as Histological Surveillance, Endometrial Sampling, Hysteroscopy Procedure

  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) also known as Pelvic MRI, Transvaginal Ultrasound, Imaging Surveillance Procedure

  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.