Clinical trial NCT04222335: Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients
Official title: Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Cancer, Nonsmall Cell
Keywords: Lung cancer
Targeted therapy
resistance
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: National Cancer Institute, France
First posted: 2020-01-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: LUNG-RESIST is a translational, monocentric and prospective research study on 40 patients whose objective is to characterize Drug Tolerant Cell (DTC) type cells in patients with a NSCLC carrying an EGFR mutation and to discover and monitor potentials biomarkers involved in this mechanism of resistance to osimertinib. The study will be offered to patients, and for whom the therapeutic decision was decided collegially during multidisciplinary molecular meetings (molecular Tumor Board). Following informed consent, patients will be registered in a single cohort. In this study, treatment with osimertinib is not studied and will be delivered according to current recommendations

Eligibility criteria: Inclusion Criteria:

* 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 Criteria:

* 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

Primary outcomes:
measure: Rate of EGFR mutated patients for whom phenotypic characterization of DTC-like and osimertinib-tolerant tumor cells is feasible.
timeFrame: Up to one year or progression
Secondary outcomes:
measure: Rate of patients for whom the molecular characterization of DTC-like cells is successfully performed.
timeFrame: Up to one year or progression
measure: Progression-free survival (PFS)
timeFrame: Up to one year or progression or death
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Toulouse University Hospital
state: Occitanie
Study officials:
affiliation: Toulouse University Hospitals
name: Julien MAZIERES, MD; PHD
role: PRINCIPAL_INVESTIGATOR
References: