Deciphering the Molecular Traits of Non-canonical Responders to Advance Personalized Therapy in Gastric Cancer

NCT ID: NCT06877910

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 220 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-10
• Study Completion Date: 2026-01-10

Brief Summary

Retrospective-prospective observational study in which a novel whole-exome sequencing (WES) approach will be used in association with whole-transcriptome sequencing (WTS) to analyze two independent and equally sized cohorts of patients with mGC.

Detailed Description

A workflow specifically designed for this project will be adopted, using clinical outcomes as a benchmark for comparative analyses, to generate a molecular classifier applicable to all patients affected by metastatic gastric cancer mGC and predict atypical tumor responses. Molecular features differently represented in exceptional responders and fast progressors will be monitored by liquid biopsy in patients included in cohort B, consisting of a validation set, leveraging a high-sensitivity technological level that allows to detect both genomic alterations and expression at the transcription level.

In addition, CSCs isolated from fast progressors will be studied with over 1,000 antitumor agents to discover vulnerabilities not currently known.

Conditions

Metastatic Gastric Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Retrospective, identification set

A workflow based on numerous statistical analyses will assign the individual molecular outcomes in one of the three categories considered (exceptional responders, conventional responders, fast progressors). The information retrieved with this first level of analysis will be summarized in a single tool for the prediction of individual risk (nomogram). In order to guarantee reproducibility, the prognostic classifier will be obtained from a retrospective cohort of patients with mGC treated with standard first-line chemotherapy.

No interventions assigned to this group

Prospective, validation set

Definition of the evolutionary trajectories of atypical responders mGC, by taking blood samples from patients enrolled in the prospective cohort, collected at predefined time points. The serial collection of blood samples will allow the study of circulating nucleic acids (cfTNA, liquid biopsy) for the monitoring of genomic alterations and for the levels of gene expression differentially represented in exceptional responders and fast progressors.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Age >18 years;
• Histological diagnosis of locally advanced or metastatic gastric cancer (GC) or gastroesophageal junction carcinoma (EJC);
• Adequate biological material for molecular analysis, collected (at surgery or by biopsy) before the administration of any anti-tumor treatment (chemotherapy and/or radiotherapy);
• ECOG PS 0-2;
• Adequate hematological, hepatic and renal function;
• Measurable disease according to RECIST criteria;
• Written informed consent.

Exclusion Criteria

• Previous chemotherapy for metastatic disease;
• Comorbidities not controlled with adequate medical therapy;
• Brain metastases;
• Patient unable to give adequate consent to the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regina Elena Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

IRCCS National Cancer institute

Rome, , Italy

Countries

Italy

Other Identifiers

RS1377/20(2378)

Identifier Type: -

Identifier Source: org_study_id