RecruitingNot ApplicableNCT04222335

Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients

Sponsor

University Hospital, Toulouse

Enrollment

80 participants

Start Date

Mar 26, 2021

Study Type

INTERVENTIONAL

Conditions

Lung Cancer, Nonsmall Cell

Summary

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) are effective therapies for advanced lung cancer patients bearing EGFR-activating mutations, but are not curative due to the invariable apparition of resistances. The investigator team have identified a new phenotype related to drug tolerance after EGFR-TKI treatment that shares several characteristics of a known process of Therapy-Induced Senescence (TIS), which could be a major event of drug tolerance in patients. Using cutting-edge technologies, patient-derived xenografts (PDX) and circulating tumor cells (CTC), the investigator team will perform an exhaustive characterization of the phenotypic and molecular changes associated with this drug-tolerant state in patients. Their results should lead to new therapeutic approaches to eliminate the reservoir of drug-tolerant cells and to prevent emergence of resistance mutations responsible for the relapse of patients.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

Patient with non operable and / or metastatic non-small cell lung cancer documented histologically.
Pathological diagnosis of NSCLC carrying an EGFR activating mutation associated with sensitivity to the tyrosine kinase inhibitors (TKI) (exons 18, 19 and 21).
Sufficient tissue sample quantity and quality for translational research
Naïve TKI-treated EGFR patient who can receive first-line treatment with Osimertinib or second-line after chemotherapy

Exclusion Criteria6

Any patient with an exon 20 EGFR mutation.
Any disease or pathology that recommend not to perform blood samples collection
Any psychological, family, geographical or social condition that could potentially, according to the investigator's judgment, prevent the collection of informed consent or interfere with compliance with the study protocol
Patient with a resistance mutation of EGFR
Patient under State Medical Assistance
Patient deprived of liberty on administrative or judicial decision, or patient under guardianship, curatorship or safeguard of justice

Interventions

OTHERBlood samples

Each participant will be followed-up regularly as part of the usual practice for imaging and medical consultations. During their visits, from inclusion (T0) to the end of study participation (T progression), each patient will have a blood sampling specifically for the research to analyze tumor DNA and circulating tumor cells: T0, T1month, T3 months, Tn months, T DNA C+, T progression. This research does not include any other act or intervention specifically required for its purposes.