MUT-ONC: Prospective Study on Resistance-associated Mutations in Metastatic Lung Cancer

Sponsor

University of Milano Bicocca (Other)

Overall Status

Recruiting

CT.gov ID

NCT06081270

Collaborator

(none)

Enrollment

Location

36.6

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Other: Liquid biopsy

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Dec 12, 2021

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Outcome Measures

Primary Outcome Measures

Identification of mutation during therapy with selective inhibitors [At treatment initiation (baseline), up to 12 weeks from treatment initiation, at the date of first documented progression, assessed up to 24 months from treatment initiation]
Evaluation of mutations in ALK (anaplastic lymphoma kinase), ROS1 (ROS proto-oncogene 1), RET, NTRK, MET, KRAS (Kirsten rat sarcoma) and BRAF and in a panel of other known oncogenes during therapy with selective inhibitors by the means of liquid biopsy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Over 18 years of age.
Histological diagnosis of inoperable metastatic or locally advanced lung cancer.
Positivity for ALK, ROS1, MET, RET (Rearranged during transfection), NTRK (NEUROTROPHIC TYROSINE RECEPTOR KINASE) rearrangements, or KRAS (Kirsten rat sarcoma)-G12C (glycine 12 cysteine) or BRAF-V600E (valine 600 glutamate) mutations, detected by validated method (IHC Immunohistochemistry 3+, FISH (fluorescence in situ hybridization) or Next Generation Sequencing).
Patients undergoing radiological progression according to RECIST 1.1 criteria to treatment with generation I, II or III inhibitors in any line of treatment. Patients may also have been pre-treated with chemotherapy in earlier lines.
Presence of measurable disease on radiological investigations. Patients with brain metastases, even as a single site of disease, are eligible for the study.
Informed consent freely given and obtained before the start of the study.

Exclusion Criteria:

Under 18 years of age
Unconfirmed histological diagnosis
Absence of rearrangement or mutation of ALK, ROS1, MET, RET, NTRK, KRAS-G12C or BRAF-V600E
Progression to chemotherapy in the absence of treatment with TKI or RAS or BRAF inhibitor
Unmeasurable disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fondazione IRCCS San Gerardo dei Tintori	Monza	MB	Italy	20900

Sponsors and Collaborators

University of Milano Bicocca

Investigators

Principal Investigator: Diego Cortinovis, MD, Fondazione IRCCS San Gerardo dei Tintori, Monza
Study Chair: Luca Mologni, PhD, University of Milano Bicocca