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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04222335
Recruitment Status : Not yet recruiting
First Posted : January 9, 2020
Last Update Posted : January 9, 2020
Institut National de la Santé Et de la Recherche Médicale, France
National Cancer Institute, France
Information provided by (Responsible Party):
University Hospital, Toulouse

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.

Condition or disease Intervention/treatment Phase
Lung Cancer, Nonsmall Cell Other: Blood samples Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: No masking
Primary Purpose: Treatment
Official Title: Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Blood sampling
Blood sampling
Other: Blood 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.

Primary Outcome Measures :
  1. Rate of EGFR mutated patients for whom phenotypic characterization of DTC-like and osimertinib-tolerant tumor cells is feasible. [ Time Frame: Up to one year or progression ]
    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

Secondary Outcome Measures :
  1. Rate of patients for whom the molecular characterization of DTC-like cells is successfully performed. [ Time Frame: Up to one year or progression ]
    This rate id defined by the number of patients who are successful compared to the total number of patients. Failure is defined by a patient with circulating tumor cells for which molecular characterization of DTC-like cells could not be performed at all measurement times.

  2. Progression-free survival (PFS) [ Time Frame: Up to one year or progression or death ]
    PFS is defined as the delay between the date of the patient's inclusion and the date of progression or death. Patients alive and without progression will be censored on the date of last news or on the date of initiation of a new anti-cancer therapy (if applicable).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04222335

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Contact: Julien MAZIERES, MD; PHD +33 5 67 77 18 37

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Toulouse University Hospital
Toulouse, Occitanie, France, 31300
Contact: Sandra BERNARD    +33 5 61 77 85 73   
Principal Investigator: Julien MAZIERES, MD; PHD         
Sub-Investigator: Laurence BIGAY-GAME, MD; PHD         
Sub-Investigator: Christophe HERMANT, MD; PHD         
Sub-Investigator: Gavin PLAT, MD; PHD         
Sub-Investigator: Audrey RABEAU, MD; PHD         
Sub-Investigator: Nicolas GUIBERT, MD; PHD         
Sub-Investigator: Myriam DELAUNAY, MD         
Sponsors and Collaborators
University Hospital, Toulouse
Institut National de la Santé Et de la Recherche Médicale, France
National Cancer Institute, France
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Principal Investigator: Julien MAZIERES, MD; PHD Toulouse University Hospitals

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Responsible Party: University Hospital, Toulouse Identifier: NCT04222335    
Other Study ID Numbers: RC31/18/0475
Numéro ID RCB : 2019-A02440-57 ( Other Identifier: ANSM )
First Posted: January 9, 2020    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Toulouse:
Lung cancer
Targeted therapy
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms