Back to results

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

Primary Purpose

Lung Cancer, Nonsmall Cell

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Blood samples

About this trial

This is an interventional treatment trial for Lung Cancer, Nonsmall Cell focused on measuring Lung cancer, Targeted therapy, resistance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Toulouse University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Blood sampling

Arm Description

Blood sampling

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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.

Progression-free survival (PFS)

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).

Full Information

NCT ID

NCT04222335

First Posted

December 17, 2019

Last Updated

May 11, 2023

Sponsor

University Hospital, Toulouse

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, National Cancer Institute, France

1. Study Identification

Unique Protocol Identification Number

NCT04222335

Brief Title

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

Acronym

LUNG-RESIST

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 26, 2021 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Toulouse

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, National Cancer Institute, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer, Nonsmall Cell

Keywords

Lung cancer, Targeted therapy, resistance

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Masking Description

No masking

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Blood sampling

Arm Type

Other

Arm Description

Blood sampling

Intervention Type

Other

Intervention Name(s)

Blood samples

Intervention Description

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 Measure Information:

Title

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

Description

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

Time Frame

Up to one year or progression

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Up to one year or progression

Title

Progression-free survival (PFS)

Description

Time Frame

Up to one year or progression or death

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Julien MAZIERES, MD; PHD

Phone

+33 5 67 77 18 37

mazieres.j@chu-toulouse.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Julien MAZIERES, MD; PHD

Organizational Affiliation

Toulouse University Hospitals

Official's Role

Principal Investigator

Facility Information:

Facility Name

Toulouse University Hospital

City

Toulouse

State/Province

Occitanie

ZIP/Postal Code

31300

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sandra BERNARD

Phone

+33 5 61 77 85 73

bernard.s@chu-toulouse.fr

First Name & Middle Initial & Last Name & Degree

Julien MAZIERES, MD; PHD

First Name & Middle Initial & Last Name & Degree

Laurence BIGAY-GAME, MD; PHD

First Name & Middle Initial & Last Name & Degree

Christophe HERMANT, MD; PHD

First Name & Middle Initial & Last Name & Degree

Gavin PLAT, MD; PHD

First Name & Middle Initial & Last Name & Degree

Audrey RABEAU, MD; PHD

First Name & Middle Initial & Last Name & Degree

Nicolas GUIBERT, MD; PHD

First Name & Middle Initial & Last Name & Degree

Myriam DELAUNAY, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs