Improving Endometrial Cancer Assessment by Combining Genomic Profiling and Surgical Assessment (EUGENIE)

Improving Endometrial Cancer Assessment by Combining the New techniqUe of GENomic Profiling With Surgical Extra uterIne disEase Assessment

EUGENIE is a prospective multicentre interventional study, focused on improving endometrial cancer (EC) assessment by combining the new technique of genomic profiling with surgical extra uterine disease assessment. The investigators aim to correlate EC stage to each of the molecular subgroups of disease and thereby guide surgical treatment and staging of EC by determining the association between molecular classification and disease stage and evaluating if and how disease stage in each of the molecular subgroups associates with prognosis.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Procedure: total hysterectomy with bilateral salpingo-oophorectomy, lymph node staging and comprehensive peritoneal staging

Detailed Description

Current treatment for endometrial cancer (EC) includes a hysterectomy with bilateral salpingo-oophorectomy. Further surgical staging procedures (lymphadenectomy, peritoneum, and/or omentum biopsies) can be performed in order to detect metastases and determine the disease stage. The type and extent of this surgical staging depend on a pre-operative risk assessment and guides adjuvant treatment (chemo- or radiotherapy). However, this pre-operative risk assessment based on histology and imaging is relatively inaccurate: first, preoperative histology presents high intersubjective variability leading to poor reproducibility in the assignment of histotype and the concordance between preoperative histology and final histology is poor. In addition, preoperative imaging modalities are expensive, time-consuming, hampered by non-perfect accuracies, require specialized expertise, or present limitations in reproducibility and availability. As a result, this leads to an incorrect risk estimation of metastases at diagnosis in EC patients with a consequent over- or undertreatment of patients. Thus, there is an urgent need to develop risk stratification strategies that will better predict the presence and localization of metastases in EC patients and therefore more efficiently tailor surgical staging procedures.

In 2013 The Cancer Genome Atlas (TCGA) Research Network developed a new molecularly driven classification system, that divides EC tumours into the well-known four molecular subgroups (POLE, MMRd, p53abn, NSMP) and has shown to surpass histologic subtyping and grading to more efficiently predict prognosis. However, the relation between the four molecular subgroups and the risk of tumour spread beyond the uterus at diagnosis has insufficiently been investigated so far and, as a consequence, surgical staging should not yet be adapted based on the molecular endometrial cancer subtype.

Thus, new studies are needed to assess the value of surgical staging in this molecular era and EUGENIE Study has been developed to bridge this knowledge gap.

The investigators believe that the future is in integrating morphologic and molecular findings, so the preoperative diagnosis will also support accurate surgical decision making and therefore a more tailored management of all EC patients.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frédéric Amant, MD, PhD; Phone Number: +3216342194; Email: frederic.amant@uzleuven.be
• Study Contact Backup: Name: Ayaka Wakatsuki, Msc; Phone Number: +3216344169; Email: ayaka.wakatsuki@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Gasthuisberg, Katholieke Universiteit Leuven
    • Principal Investigator: Frédéric Amant, MD, PhD
    • Contact: Ayaka Wakatsuki; Phone Number: +32 16 34 41 69; Email: ayaka.wakatsuki@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntary written informed consent of the participant or their legally authorized representative has been obtained before any screening procedures
• Women ≥ 18 years
• First diagnosis of EC, all disease stages and all histo-types

Exclusion Criteria:

• Participant has a history of pelvic or para-aortic lymph node dissection or sampling, previous pelvic (and/or para-aortic) radiotherapy, previous neoadjuvant chemotherapy
• Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
• Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All women older than 18 newly diagnosed with endometrial cancer of all stages and histotypes; All patients must undergo total hysterectomy and bilateral salpingo-oophorectomy or bilateral salpingectomy if premenopausal status and the lymph-node assessment according to European guidelines and local protocol. A comprehensive surgical peritoneal staging is required, which includes omentectomy/omental biopsies and six peritoneal biopsies.

Procedure: total hysterectomy with bilateral salpingo-oophorectomy, lymph node staging and comprehensive peritoneal staging; Surgical treatment will consist of total hysterectomy with bilateral salpingo-oophorectomy according to international guidelines. In low- and intermediate-risk EC patients, staging will include a sentinel lymph node (SLN) procedure. In high intermediate-risk and high-risk EC patients, lymph node staging will involve SLN procedure and/or pelvic and para-aortic lymph node dissection (LND), depending on the local protocol. The Study-related procedures include infracolic omentectomy or two separate omental representative biopsies, biopsies of all suspicious lesions as well as six peritoneal sites (bladder, pouch of Douglas, bilateral paracolic gutter and bilateral diaphragm). Stage IV patients will be treated according to European guidelines. When feasible, full surgical intervention (i.e. debulking) is recommended. If this cannot be achieved, a radiologic and/or histologic confirmation of tumor spread beyond the uterus will be accepted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial cancer stage	Endometrial cancer stage assessed according to the 2009 an 2023 International Federation of Gynecology and Obstetrics (FIGO) staging	72 months
Molecular type of endometrial cancer	Tumor classification using the molecular classification as proposed by either ProMisE or TRANSPORTEC. Groups will be classified as follows: MMR: Mismatch Repair Protein Status will be determined as a surrogate for microsatellite instability (MSI) by considering the immunohistochemical (IHC) staining of the MMR proteins. In case of loss of staining of one or more MMR proteins, the EC will be classified as MMR deficient (MMRd), otherwise, the carcinoma will be coded as MMR proficient (MMRp).; POLE: if the POLE exonuclease domain mutations (EDM) gene is mutated (i.e. a pathogenic mutation), the tumour will be classified as POLE.; p53 IHC: TP53 mutation status will be determined via IHC and in case of inconclusive p53 staining, also sequencing.; NSMP: a carcinoma that has not been stratified into groups 1), 2) or 3) will be categorized into the NSMP (no specific molecular profile or copy number low).	72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	72 months
Time to recurrence	Time to recurrence	72 months

Collaborators and Investigators

• Sponsor: University Hospital, Gasthuisberg
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; University Medical Centre Maribor
• Investigators: Principal Investigator: Frédéric Amant, MD, PhD, UZ Leuven Gasthuisberg

Publications and helpful links

Helpful Links

• Protocol

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Endometrial Cancer; Genomic profiling; Molecular classification; Disease staging
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms
• Other Study ID Numbers: S66928

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No