Prospective Study on Resistance-associated Mutations in Metastatic Lung Cancer

NCT06081270 | Unknown

• 1 other identifier: MUT-ONC
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer

Keywords

ALK (anaplastic lymphoma kinase); ROS (ROS proto-oncogene 1); RET (Rearranged during transfection); B-RAF; lung cancer; tyrosine kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• Identification of mutation during therapy with selective inhibitors

  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

  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

Interventions

Liquid biopsy OTHER

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Twenty patients will be enrolled in the study

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Milano Bicocca: lead

Study Sites (1)

Fondazione IRCCS San Gerardo dei Tintori

Monza, MB, 20900, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Lung Neoplasms; Multiple Endocrine Neoplasia Type 2a

Interventions

Liquid Biopsy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Investigative Techniques

Study Officials

• Diego Cortinovis, MD

  Fondazione IRCCS San Gerardo dei Tintori, Monza

  PRINCIPAL INVESTIGATOR

• Luca Mologni, PhD

  University of Milano Bicocca

  STUDY CHAIR

Central Study Contacts

Clinical Trial Administration

CONTACT

+390392333203; onco.noprofit@gmail.com

Luca Mologni, PhD

CONTACT

luca.mologni@unimib.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: October 13, 2023
• Study Start: December 12, 2021
• Primary Completion: April 30, 2024
• Study Completion: December 31, 2024
• Last Updated: October 13, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: After publication
• Access Criteria: Upon request

Locations

IT (1)