Lung Cancer, Nonsmall CellLUNG-RESISTNCT04222335
Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients
A study testing Blood samples in people with Lung Cancer, Nonsmall Cell, run by University Hospital, Toulouse at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Nonsmall Cell
- What is being tested?
- Blood samples
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteFrance
- Study dates
- 26 Mar 2021to 21 Apr 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Conditions
- Lung Cancer, Nonsmall Cell
- Being tested
- Blood samples
- Keywords
- Lung cancer, Targeted therapy, resistance
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplesOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Blood sampling | Other | Blood sampling Receives: Other: Blood samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to one year or progression
Secondary outcomes (2)
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.
Measured: Up to one year or progression
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).
Measured: Up to one year or progression or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2020
- Study start26 Mar 2021
- Primary completion21 Apr 2026
- Study completion21 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Cancer, Nonsmall CellStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, National Cancer Institute, France
- Responsible party
- Sponsor
- Investigators
- Julien MAZIERES, MD; PHD, Principal investigator, Toulouse University Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04222335
- Sponsor's protocol ID
- RC31/18/0475
- Other IDs
- Numéro ID RCB : 2019-A02440-57
- Acronym
- LUNG-RESIST
- Status last verified
- Aug 2026
- First submitted
- 17 Dec 2019
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients
- ClinicalTrials.gov ID
- NCT04222335
- Acronym / sponsor ID
- LUNG-RESIST / RC31/18/0475
- Conditions
- Lung Cancer, Nonsmall Cell
- Keywords
- Lung cancer, Targeted therapy, resistance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, National Cancer Institute, France
- Study start
- 26 Mar 2021 (actual)
- Primary completion
- 21 Apr 2026 (actual)
- Study completion
- 21 Apr 2026 (actual)
- First posted
- 9 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blood sampling | Other | Other: Blood samplesBlood sampling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samplesEach 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. | Other | Blood sampling |
Primary outcome
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
2 secondary outcomes
Rate of patients for whom the molecular characterization of DTC-like cells is successfully performed.
Time frame: Up to one year or progression
Progression-free survival (PFS)
Time frame: Up to one year or progression or death
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julien MAZIERES, MD; PHD principal investigator
Toulouse University Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood samples in people with Lung Cancer, Nonsmall Cell, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.