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

NCT04222335 | Active Not Recruiting

• 2 other identifiers: RC31/18/0475Numéro ID RCB : 2019-A02440-57
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer, Nonsmall Cell

Keywords

Lung cancer; Targeted therapy; resistance

Outcome Measures

Primary Outcomes (1)

• Rate of EGFR mutated patients for whom phenotypic characterization of DTC-like and osimertinib-tolerant tumor cells is feasible.

  Rate of EGFR mutated patients for whom the DTC phenotype has been characterized at T0 (Baseline), T1 month, T3 month, Tn month, T antideoxyribonuclease (ADN) Circulant+, T progression

  Up to one year or progression

Secondary Outcomes (2)

• Rate of patients for whom the molecular characterization of DTC-like cells is successfully performed.

  Up to one year or progression

• Progression-free survival (PFS)

  Up to one year or progression or death

Study Arms (1)

Blood sampling

OTHER

Blood sampling

Other: Blood samples

Interventions

Blood samples OTHER

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.

Blood sampling

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• National Cancer Institute, France: collaborator

Study Sites (1)

Toulouse University Hospital

Toulouse, Occitanie, 31300, France

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Julien MAZIERES, MD; PHD

  Toulouse University Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: January 9, 2020
• Study Start: March 26, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)