NCT06081270

Prospective Study on Resistance-associated Mutations in Metastatic Lung Cancer

Prospective Study on Resistance-associated Mutations in Metastatic Lung Neoplasm Patients With Alterations in Driver Oncogenes, Except EGFR, Undergoing Treatment With Specific Inhibitors

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 20 (estimated)
• Sponsor: University of Milano Bicocca · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This single-centre prospective study is aimed at analysing, by means of liquid biopsy with next generation sequencing analysis on circulating tumor DNA, resistance mutations arising during therapy with selective inhibitors in patients with RTK-positive NSCLC or with mutations in the Ras/MAPK (mitogen-activated protein kinase) pathway, treated at the San Gerardo Hospital, Monza.

Detailed description

Non-small-cell lung cancer (NSCLC) is a heterogeneous disease that may have several genetic alterations in oncogenes responsible for progression. 30-40% of NSCLC patients carry mutations affecting the Ras/MAPK pathway, while alterations in receptor tyrosine kinases (RTKs) are found in approximately 25-35% of cases. More than half of the latter are in the Epithelial Growth Factor Receptor (EGFR) gene and have been extensively studied. In the remaining cases, several genes are involved, each with lower frequencies, ranging from around 1% to 5%, depending on the studies. Despite the wide availability of inhibitors, progression remains inevitable due to the emergence of drug resistance mechanisms. The mechanisms by which resistance can be established are essentially of three types: amplification of the target gene, activation of other signal translation pathways (by-pass track) and the occurrence of mutations in the tyrosine kinase domain of the target protein. Liquid biopsy with circulating tumour DNA (ctDNA) analysis provides a non-invasive surrogate method to identify somatic mutations by means of a simple blood sample, without risk to the patient. Moreover, liquid biopsy, by collecting ctDNA from different metastatic sites, could better reflect tumour heterogeneity, both spatial and temporal, and could, therefore, constitute a simple method of longitudinal monitoring during treatment, possibly making it possible to identify relapse early before clinical manifestation. This single-centre prospective study is aimed at analysing, by means of liquid biopsy with next generation sequencing analysis on ctDNA, resistance mutations arising during therapy with selective inhibitors in patients with RTK-positive NSCLC or with mutations in the Ras/MAPK pathway, treated at the San Gerardo Hospital, Monza.

Conditions

• Lung Cancer

Interventions

Type	Name	Description
OTHER	Liquid biopsy	Blood withdrawal for each patient is performed (i) at the time of treatment initiation with tyrosine kinase inhibitors (TKI); (ii) at the time of the first planned instrumental re-evaluation according to clinical practice regardless of the type of response to the TKI employed (9-12 weeks); (iii) at the time of radiological progression according to RECIST 1 criteria. 1 at computerized tomography scan with contrast or metabolic progression at 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose during TKI therapy; (iv) at the time of the change of therapeutic strategy decided by the investigator when used beyond progression and not coinciding with point iii. The ctDNA is extracted from plasma and analyzed with Illumina sequencing method.

Timeline

• Start date: 2021-12-12
• Primary completion: 2024-04-30
• Completion: 2024-12-31
• First posted: 2023-10-13
• Last updated: 2023-10-13

Locations

1 site across 1 country: Italy