Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on Prognosis

Endometrial Cancer Clinical Trial

Official title:

Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on Prognosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06206083
• Other study ID #: (023/028/ICI/(CEI/017/23)
• Status: Recruiting
• Start date: March 1, 2024
• Est. completion date: February 1, 2027

Study information

• Verified date: February 2024
• Source: National Institute of Cancerología
• Contact: David F Cantu-de-León, PhD
• Phone: +52-55-5628-0400
• Email: dfcantu[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Endometrial cancer (EC) is one of the most common gynecological neoplasms, being the second in incidence and third in mortality in Mexico. Recent studies show that EC molecular classification (Cancer Genome Atlas Research Network, 2013) serves to establish a more accurate prognosis in these patients and regulate therapeutic behavior in a personalized manner. However, there are no studies on EC molecular classification in Mexican women or its impact on prognosis and the possible modification of targeted treatment. The investigators will determine the molecular classification in EC by next-generation sequencing (NGS) to detect TP53 and POLE somatic mutations, and immunohistochemical detection of microsatellite instability (MSH2, MLH1, PMS1, PMS2, MSH6, and MSH3) in a cohort of patients with endometrioid-type EC, endometrioid subtype, attended at the Instituto Nacional de Cancerología - Mexico (INCan) and determine its impact on clinical prognosis.

Description:

The investigators will carry out a pilot study on patients with endometrioid type EC treated between 2015-2019. Samples of patients over 18 years of age admitted to the cohort with a diagnosis of endometrioid-type EC are already collected and will be evaluated for exome sequencing (N=32) and the detection of POLE mutations. DNA will be extracted using the "DNA/RNA AllPrep" kit (QIAGEN). Verification of adequate DNA extraction will be performed by quantifying using TapeStation (Agilent). Exome sequencing (N = 32 tumor samples and 32 somatic samples [leukocytes] from the same patient) will be carried out using Illumina's Nextera Rapid Capture Exome at Azenta Life Science (NJ, USA) following preset protocols and with a depth of 100X. The alignment and detection of variants will be done with the GATX-Mutect Suite (Broad Institute, USA) and the annotation of variant filtering with ANNOVAR. The identification of hotspots will be made according to Chen study. The immunohistochemistry (IHC) for microsatellite instability and overexpressed mutant TP53 (N = 94) will be done using established IHC protocols and will include MSH2, MLH1, PMS1, PMS2, MSH6, MSH3, and TP53.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: February 1, 2027
• Est. primary completion date: November 1, 2026
• Gender: Female
• Age group: 18 Years and older

Eligibility

Criteria: Inclusion Criteria:

• Clinical diagnosis of endometrioid-type endometrial cancer with samples available

• That the patients have undergone surgery at INCan.

Exclusion Criteria:

• Samples with CEE of non-endometroid type.

• Samples from patients with double primary neoplasm, including carcinoma ductal in situ, squamous cell skin cancers, and cervical carcinoma in situ

• History of malignancy < 5 years prior with no evidence of disease (i.e., remission).

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Genetic:
• Descriptive and analytical
Patients with EC endometroid

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cancerología	Mexico City	Cdmx

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Cancerología	GlaxoSmithKline

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	sequence the exome	Molecular classification of endometroid-type endometrial cancer in Mexican participants based on POLE and TP53 mutations as well as makers of microsatellite instability (MSH2, MLH1, PMS1, PMS2, MSH6, and MSH3).	2024-2025
Primary	Determine POLE mutations	Determine POLE mutations by massive next-generation sequencing of a discovery cohort in patients with endometroid-type EC.	2024-2025
Primary	Determine microsatellite instability	To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC.	2025-2026
Primary	Validation	To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC.	2025-2026
Secondary	Overall survival	To describe the overall survival of molecular types of endometroid-type EC in INCan patients.	2025-2026
Secondary	Disease-free surviva	To describe the disease-free survival of the molecular types of endometroid-type EC in INCan patients.	2025-2026