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

Regina Elena Cancer Institute

Status: Active, not recruiting

Conditions: Metastatic Gastric Cancer

Study type: Observational

Funder types: Other

Identifiers

NCT06877910

RS1377/20(2378)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

220 participants in 2 patient groups

Retrospective, identification set

Description:

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.

Prospective, validation set

Description:

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.