Improving Endometrial Cancer Assessment by Combining Genomic Profiling and Surgical Assessment

Endometrial Cancer Clinical Trial

— EUGENIE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06354738
• Other study ID #: S66928
• Status: Recruiting
• Phase: N/A
• Start date: January 16, 2023
• Est. completion date: November 1, 2028

Study information

• Verified date: April 2024
• Source: University Hospital, Gasthuisberg
• Contact: Frédéric Amant, MD, PhD
• Phone: +3216342194
• Email: frederic.amant[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: November 1, 2028
• Est. primary completion date: November 1, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Belgium	UZ Gasthuisberg, Katholieke Universiteit Leuven	Leuven

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Gasthuisberg	Fondazione Policlinico Universitario Agostino Gemelli IRCCS, University Medical Centre Maribor

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endometrial cancer stage	Endometrial cancer stage assessed according to the 2009 an 2023 International Federation of Gynecology and Obstetrics (FIGO) staging	72 months
Primary	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	Overall survival	Overall survival	72 months
Secondary	Time to recurrence	Time to recurrence	72 months

External Links

•   Protocol