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

May 8, 2026 updated by: Jorge García Fernández, Hospital Universitari de Bellvitge

SHAPE-ENDO (Strategic Hormonal Approach & Prehabilitation in Endometrial Cancer): A Low-Intervention, Single-Arm, Non-Randomized Clinical Trial of Multimodal Metabolic and Surgical Optimization in Patients With Atypical Endometrial Hyperplasia or Early-Stage Endometrial Cancer and BMI ≥40 kg/m²

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Obesity is a major modifiable risk factor for endometrial cancer and is associated with increased surgical complexity, higher perioperative morbidity, and reduced eligibility for minimally invasive surgery. In patients with severe obesity and early-stage endometrial disease, overall mortality may be substantially influenced by metabolic and cardiovascular comorbidities. Therefore, strategies aimed at improving metabolic health and functional status before definitive surgery may have important implications for perioperative and long-term outcomes.

In selected patients with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage, low-risk endometrioid endometrial carcinoma, temporary conservative hormonal management with a levonorgestrel-releasing intrauterine device with or without oral progestins can provide local disease control under close histological surveillance. Semaglutide, a GLP-1 receptor agonist, has demonstrated clinically relevant weight loss and cardiometabolic benefits in patients with obesity.

SHAPE-ENDO evaluates a protocolized multimodal strategy integrating semaglutide-based metabolic optimization, local hormonal therapy, nutritional intervention, structured exercise, and close oncologic surveillance. The trial is designed as a low-intervention, single-arm, non-randomized clinical trial because the treatments used are authorized, applied according to clinical indication and routine care, and do not involve placebo or high-risk experimental procedures.

A pre-specified interim descriptive analysis will be performed when approximately 50% of the planned prospective cohort has completed the primary assessment time point.

Study Type

Interventional

Enrollment (Estimated)

82

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Study Population

Adult women with early-stage, low/intermediate-risk endometrioid endometrial cancer or atypical hyperplasia/EIN and BMI ≥35 kg/m² receiving multimodal metabolic-hormonal prehabilitation prior to surgery.

Description

Inclusion Criteria:

  • Women ≥18 years old.
  • Histologically confirmed Atypical Endometrial Hyperplasia / EIN or low-risk endometrioid endometrial carcinoma (G1-G2), confined to uterine body.
  • Classified as low/intermediate risk per ESGO-ESTRO-ESP 2025; presurgical stages IA1, IA2 or IB.
  • Negative or focal LVSI (if available).
  • Molecular subgroups: POLEmut, p53wt, MMRd or NSMP ER+.
  • BMI ≥40kg/m² at inclusion.
  • Acceptance of temporary conservative management and ability to follow multimodal optimization strategy.
  • Ability to understand and sign informed consent.

Exclusion Criteria:

  • FIGO stages IA3, IC, II or higher.
  • Positive lymphovascular invasion.
  • High-risk molecular: p53mut or NSMP ER-negative.
  • Non-endometrioid histologies (serous, clear cell, carcinosarcoma, mixed, etc.).
  • Metastatic or extra-uterine disease.
  • Contraindication to GLP-1RA or progestogens.
  • Previous pancreatitis, MEN-2, medullary thyroid carcinoma.
  • Participation in another pharmacological trial.
  • Any condition that in investigator judgment impairs safety or compliance.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SHAPE-ENDO Cohort

Women with BMI ≥40 kg/m² and atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage, low-risk endometrioid endometrial cancer assigned to the protocolized SHAPE-ENDO multimodal optimization strategy. The strategy includes semaglutide/GLP-1 receptor agonist therapy, levonorgestrel-releasing intrauterine device with or without oral progestins, structured nutritional intervention, adapted physical exercise, and scheduled oncologic surveillance.

Treatments are authorized and used according to clinical indication, approved labeling, and routine clinical care.
Behavioral: 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.
Other Names:
  • Nutritional Counseling
  • Hypocaloric diet program
  • Dietary Prehabiilitation
Behavioral: 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
Other Names:
  • Exercise Prehabilitation
  • Supervised Physical Activity Program
  • Combined Aerobic and Strength Training
Procedure: 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.
Other Names:
  • Hysteroscopy
  • Histological Surveillance
  • Endometrial Sampling
Procedure: 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.
Other Names:
  • Pelvic MRI
  • Transvaginal Ultrasound
  • Imaging Surveillance
Drug: 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.
Other Names:
  • Semaglutide
Device: 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.
Other Names:
  • LNG-IUD
Drug: 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.
Other Names:
  • Medroxyprogesterone acetate
  • Megestrol acetate
  • Progestin therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients achieving predefined metabolic and clinical optimization criteria
Time Frame: Up to 12 months
Optimization is defined as achieving ≥12-15% total body weight loss and/or reduction to BMI <35 without evidence of tumor progression on histologic or radiologic assessment, enabling eligibility for minimally invasive surgery. Metabolic parameters (weight, BMI, waist circumference, HbA1c, blood pressure, and lipid profile) are recorded longitudinally. Progression is assessed through scheduled endometrial biopsy and imaging.
Up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Glycated Hemoglobin (HbA1c)
Time Frame: Baseline to 6 months and Baseline to 12 months
Change from baseline in glycated hemoglobin (HbA1c, %) measured using standard clinical laboratory assays as a marker of glycemic control and cardiometabolic risk.
Baseline to 6 months and Baseline to 12 months
Histological Complete Response Rate of Endometrial Lesion
Time Frame: Baseline to 6 months and 12 months

Percentage of patients achieving complete histological response of the endometrial lesion assessed by endometrial biopsy with or without hysteroscopy. Histological evaluation is performed by gynecologic pathologists using standardized pathological criteria. Complete response is defined as absence of endometrial carcinoma or atypical hyperplasia on biopsy during follow-up.

Unit of Measure: Percentage of patients (%).
Baseline to 6 months and 12 months
Proportion of patients reaching eligibility for minimally invasive surgery
Time Frame: Up to 12 months
Proportion of patients who meet predefined clinical criteria for minimally invasive hysterectomy after multimodal optimization, including adequate metabolic improvement, anesthetic clearance, functional capacity, and absence of disease progression on pathology or imaging. Eligibility is determined by the multidisciplinary tumor board and surgical team.
Up to 12 months
Change in Health-Related Quality of Life Score (SF-36)
Time Frame: Baseline to 12 months
Change from baseline in health-related quality of life assessed using the Short Form-36 Health Survey (SF-36) questionnaire. The SF-36 evaluates multiple domains of physical and mental health. Scores range from 0 to 100, with higher scores indicating better health-related quality of life..
Baseline to 12 months
Incidence of adverse events related to standard-of-care treatments
Time Frame: Baseline to 12 months
Frequency, severity, and type of adverse events associated with standard-of-care treatments, including semaglutide and hormonal therapy. Events are documented through clinical records and routine follow-up visits, classified according to CTCAE criteria, and categorized as mild, moderate, severe, serious, or treatment-limiting. Only events occurring during active management and follow-up are included
Baseline to 12 months
Perioperative outcomes following minimally invasive surgery
Time Frame: At time of surgery and 30 days postoperatively
Perioperative outcomes in patients who undergo minimally invasive hysterectomy after optimization, including operative time, estimated blood loss, conversion to laparotomy, intraoperative complications, hospital stay, 30-day postoperative complications, and readmission. Complications will be graded according to Clavien-Dindo classification.
At time of surgery and 30 days postoperatively
Changes in anthropometric measures (BMI, waist circumference, visceral adiposity)
Time Frame: Up to 12 months
Change in BMI, waist circumference, and percent weight loss categories (≥5%, ≥10%, ≥15%). Measurements taken at scheduled visits and analyzed longitudinally to evaluate response to multimodal optimization.
Up to 12 months
Adherence to GLP-1 therapy, hormonal therapy, diet, and exercise interventions
Time Frame: Baseline to 12 months
Adherence to semaglutide, hormonal therapy (LNG-IUD ± oral progestins), dietary plan, and structured exercise program, including reasons for modification or discontinuation. Data obtained from clinical records, pharmacy dispensation, and self-reported logs.
Baseline to 12 months
Change in Fasting Plasma Glucose
Time Frame: Baseline to 6 months and Baseline to 12 months
Change from baseline in fasting plasma glucose concentration (mg/dL) measured using standard biochemical laboratory analysis.
Baseline to 6 months and Baseline to 12 months
Change in Serum Triglycerides
Time Frame: Baseline to 6 months and Baseline to 12 months
Change from baseline in serum triglyceride levels (mg/dL) measured using routine clinical laboratory lipid panel testing.
Baseline to 6 months and Baseline to 12 months
Change in HDL Cholesterol
Time Frame: Baseline to 6 months and Baseline to 12 months
Change from baseline in high-density lipoprotein (HDL) cholesterol levels (mg/dL) measured using standard lipid panel testing.
Baseline to 6 months and Baseline to 12 months
Change in LDL Cholesterol
Time Frame: Baseline to 6 months and Baseline to 12 months
Change from baseline in low-density lipoprotein (LDL) cholesterol levels (mg/dL) measured using standard lipid panel testing.
Baseline to 6 months and Baseline to 12 months
Change in Blood Pressure
Time Frame: Baseline to 6 months and Baseline to 12 months
Change from baseline in systolic and diastolic blood pressure (mmHg) measured using standard clinical sphygmomanometry during routine clinical visits
Baseline to 6 months and Baseline to 12 months
Change in C-Reactive Protein (CRP)
Time Frame: Baseline to 6 months and Baseline to 12 months
Change from baseline in serum C-reactive protein concentration (mg/L) measured using standard laboratory assays as a marker of systemic inflammation.
Baseline to 6 months and Baseline to 12 months
Change in Quality of Life Score (EORTC QLQ-C30)
Time Frame: Baseline to 12 months
Change from baseline in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The questionnaire evaluates global health status, functional scales, and symptom scales in oncology patients. Scores range from 0 to 100 according to EORTC scoring guidelines.
Baseline to 12 months
Change in Functional Capacity
Time Frame: Baseline to 12 months
Change from baseline in functional capacity assessed using standardized physical activity tolerance or performance measures recorded during clinical follow-up visits.
Baseline to 12 months
Disease-Free Survival (DFS)
Time Frame: Up to 5 years after inclusion or definitive treatment.
Time from definitive treatment or documented complete response to the first occurrence of disease recurrence, disease progression, or death from any cause, whichever occurs first. Patients without an event will be censored at the date of last available follow-up.
Up to 5 years after inclusion or definitive treatment.
Recurrence-Free Survival (RFS)
Time Frame: Up to 5 years after inclusion or definitive treatment.
Time from definitive treatment or documented complete response to the first documented recurrence of endometrial cancer. Recurrence may be defined by histological, radiological, or clinical evidence according to standard follow-up criteria. Patients without recurrence will be censored at the date of last available follow-up.
Up to 5 years after inclusion or definitive treatment.
Overall Survival (OS)
Time Frame: Up to 5 years after study inclusion.
Time from study inclusion to death from any cause. Patients alive at the end of follow-up will be censored at the date of last contact.
Up to 5 years after study inclusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitari de Bellvitge

Collaborators

Institut d'Investigació Biomèdica de Bellvitge
University of Barcelona
Hospital Universitari de Bellvitge - IDIBELL

Investigators

  • Principal Investigator: Jorge Garcia Fernandez, Hospital Universitario de Bellvitge
  • Principal Investigator: Lola Marti, Hospital Universitario de Bellvitge

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

September 1, 2028

Study Registration Dates

First Submitted

November 23, 2025

First Submitted That Met QC Criteria

March 5, 2026

First Posted (Actual)

March 10, 2026

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHAPE-ENDO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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