Non-small Cell Lung Cancer PatientsPIONeeRNCT03493581
Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)
A study testing BIOPSY, blood-sampled and feces samples in people with Non-small Cell Lung Cancer Patients, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
PIONeeR study is a prospective, multicenter study without administration of an investigational product. The promotion and funding will be done by the Assistance Publique Hôpitaux de Marseille (APHM), the coordination by AMU. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Patients
- What is being tested?
- BIOPSY, blood-sampled and feces samples
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 450 participants
- Where
- 1 siteFrance
- Study dates
- 8 Mar 2018to 12 Aug 2024
- 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
- - Patients must be over 18 years
- Patients must have histologically confirmed diagnosis of advanced (proven stade IV) or recurrent NSCLC,
- Their ECOG Performance Status must be of 0 or 1
- EITHER patients must be previously untreated and eligible for an EMA approved first line PD-1 or PD-L1 inhibitor in combination with platinum-based chemotherapy, irrespective of their tumor histology
- These EMA approved first line combinations must be reimbursed by French Health Insurance or at least, must have an Authorization for Temporary Use (ATU) in France
- OR Patients must display disease progression after at least one line of platinum-based chemotherapy and eligible for a registered second or third line PD-1 or PD-L1 inhibitor in monotherapy (to date, Nivolumab, Pembrolizumab, Atezolizumab)
Show all 11Show fewer
- For patients registered for a 2nd or 3rd line, those with known actionable molecular alteration (EGFR activating mutation, ALK rearrangement, ROS1 rearrangement) should have received a specific inhibitor
- Patients must have an available archived tissue from a standard tumor biopsy for PD-L1 assessment, done before PD-1 ICI initiation
- Patients must have an available archived tissue from a standard tumor biopsy for PD-L1 assessment, done before PD-1 ICI initiation
- Patients must have adequate organ functions
- Patients must have provided a signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
Who cannot join
- Patients previously untreated and eligible for a first line PD-1 or PD-L1 inhibitor in monotherapy
- Combination of PD-1 or PD-L1 inhibitor with bevacizumab
- Exclusive bone progression
- Exclusive cerebral progression not amenable to surgical biopsy
- Absence of a target lesion according to RECIST criteria 1.1
- Life expectancy of less than 3 months
Show all 16Show fewer
- Severe adverse events from PD-1 treatment
- Abnormal coagulation contraindicating biopsy
- History of hemorrhagic or thrombotic stroke, TIA or other CNS bleeds
- Active uncontrolled or serious infection (viral, bacterial or fungal)
- Active infection including VHB and VHC infections
- Individuals deprived of liberty or placed under the authority of a tutor
- Patient unable to understand, read and/or sign an informed consent
- Any condition which in the Investigator's opinion would jeopardize compliance with the protocol of the study
- Patients without Health insurance scheme or Universal Medical Coverage (CMU) or any equivalent scheme
- Pregnant or breast-feeding women
Trial locations and contacts
1 site in 1 country.
About this study
PIONeeR study is a prospective, multicenter study without administration of an investigational product.
The promotion and funding will be done by the Assistance Publique Hôpitaux de Marseille (APHM), the coordination by AMU. There will be 3 principal investigational clinical centres in France:
Read more
- Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques in APHM, Marseille, supervised by Prof. L. Greillier
- Medical Oncology Department of Centre Léon Bérard, Lyon, supervised by Prof. M. Pérol
- Unité d'Oncologie Thoracique, CHU Larrey /Oncopôle, Toulouse, supervised by Prof. J. Mazières.
Some secondary centres, nearby the three principal mentioned above, will be associated to ensure recruitment of patients, in accordance to provisional planning.
- The primary objective is to validate the existence and distribution of the hypothetical immune profile (within blood and tumoral tissue) explaining primary or adaptive resistance to standard PD-1 inhibitors monotherapy, in NSCLC patients.
- The secondary objectives are to better characterize :
- PK/PD relationships,
- inter-patient PK variability,
- If systemic exposure levels could be predictive of efficacy of PD-1 ICI, in NSCLC patients.
- Some exploratory objectives are :
- to assess a predictive value of a panel of endothelial biomarkers, in NSCLC patients.
- to compare predictive immune \& endothelial biomarker profiles with those of sensitive tumors.
- to better understand which profiles track significantly with progression following PD-1 ICI administration, in order to improve advanced NSCLC patients' stratification, for future clinical trials.
Read the detailed description
Visits will match with usual schedule of patient's appointments with their referent oncologist or for injections of ICIs, when blood sampling or biopsies will be done. Feces will be collected by patients themselves, at home (optional).
The same day of registration for either an EMA approved first line PD-1 or PD-L1 inhibitor in combination with platinum-based chemotherapy OR a standard 2nd or 3rd line PD-(L) 1 ICIs monotherapy (to date, Nivolumab, Pembrolizumab, Atezolizumab), 450 advanced NSCLC patients will undergo a screening visit (Vs). If they are eligible, after signing an informed written consent, they will be blood-sampled specifically for the study:
- after 3 or 4 weeks (V1-1st assessment of PK/PD, after the 2d course),
- after 6 weeks (V2),
- after 8 or 9 weeks (V3-2nd assessment of PK/PD, after the last course),
- after 12 weeks of treatment (V4- samples for 3rd assessment of PK/PD and other analyses ).
- after 18 weeks (V5- samples for 4th assessment of PK/PD and other analyses,),
- after 24 weeks of treatment (V6-5th assessment of PK/PD and other analyses).
Patients will also be re-biopsied (primitive tumor or metastasis) specifically for the study, at V2. Referent patients'oncologist will opt for the simplest technical approach with a minimal risk exposure for patients. Standard procedures will be implemented for subsequent patient's monitoring.
Patients will also provide remaining samples from pre-treatment surgical resections/biopsies (primitive tumor or metastasis).
If they are amenable to collect feces samples at home, an auto collection kit will be supplied to them, before the first injection (Vs) and when they come for the 2nd course (i.e after 3 or 4 weeks post initiation) in order to self-collect feces within the week beforeV2 - 6 weeks post initiation).
Following the last study visit (V4 or V5 or V6)or at the time of a subsequent disease progression, patients will enter to the follow up period (a minimum 24 weeks ). They will be followed by their usual referent oncologist, no additional visit is required. Subsequent response to the anti-PD (L) 1 treatment, anti-cancer therapy, survival will be collected via patient medical records and analysed for current study.
- Conditions
- Non-small Cell Lung Cancer Patients
- Being tested
- BIOPSY, blood-sampled, feces samples
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIOPSYProcedure or surgery
re-biopsy (primitive tumor or metastasis) specifically for the study, at V2(6 weeks)
blood-sampledDiagnostic test
- after 3 or 4 weeks (V1-1st assessment of PK/PD, after the 2d course),
- after 6 weeks (V2),
- after 8 or 9 weeks (V3-2nd assessment of PK/PD, after the last course),
- - after 12 weeks of treatment (V4- samples for 3rd assessment of PK/PD and other analyses ).
- after 18 weeks (V5- samples for 4th assessment of PK/PD and other analyses,),
- after 24 weeks of treatment (V6-5th assessment of PK/PD and other analyses).
feces samplesOther
If they are amenable to collect feces samples at home, an auto collection kit will be supplied to them, before the first injection (Vs) and when they come for the 2nd course (i.e after 3 or 4 weeks post initiation) in order to self-collect feces within the week beforeV2 - 6 weeks post initiation).
| Study group | Role | What they receive |
|---|---|---|
| NSCLC patients | Experimental | Not described Receives: Procedure: BIOPSY; Diagnostic Test: blood-sampled; Other: feces samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immuno-monitoring
BLOOD SAMPLES to characterize B, T, NK, and dendritic cell subsets and monocyte populations as well as Innate Lymphoid Cells (ILC) with cytometry analysis
Measured: 54 MONTHS
Secondary outcomes (6)
Measure the number of somatic mutations
BLOOD SAMPLES- extraction of nucleic acids from Plasma
Measured: 54 MONTHS
Measure the number of somatic mutations
Tumor tissues- extraction of nucleic acids
Measured: 54 MONTHS
measure the Circulating endothelial cells (CECs)
BLOOD SAMPLES using a CD146-based immunomagnetic separation assay.
Measured: 54 MONTHS
Minimum Plasma Concentration Cmin of anti PD (L) 1 treatment
BLOOD SAMPLES
Measured: 54 MONTHS
Maximum Plasma Concentration Cmax of anti PD (L) 1 treatment
BLOOD SAMPLES
Measured: 54 MONTHS
lymphocytes DNA extraction's
Relevant polymorphisms will be screened by NGS technology
Measured: 54 MONTHS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2018
- Study start8 Mar 2018
- Primary completion8 Mar 2024 (estimated)
- Study completion12 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer PatientsStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François CREMIEUX, Study director, ASSISTANCE PUBLIQUE HOPITAUX D EMARSEILLE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03493581
- Sponsor's protocol ID
- 2017-67
- Other IDs
- 2018-A03518-45
- Acronym
- PIONeeR
- Status last verified
- Jun 2023
- First submitted
- 20 Mar 2018
- Last updated
- 26 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)
- ClinicalTrials.gov ID
- NCT03493581
- Acronym / sponsor ID
- PIONeeR / 2017-67
- Conditions
- Non-small Cell Lung Cancer Patients
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 8 Mar 2018 (actual)
- Primary completion
- 8 Mar 2024 (estimated)
- Study completion
- 12 Aug 2024 (estimated)
- First posted
- 10 Apr 2018 (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.
PIONeeR study is a prospective, multicenter study without administration of an investigational product.
The promotion and funding will be done by the Assistance Publique Hôpitaux de Marseille (APHM), the coordination by AMU. There will be 3 principal investigational clinical centres in France:
- Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques in APHM, Marseille, supervised by Prof. L. Greillier
- Medical Oncology Department of Centre Léon Bérard, Lyon, supervised by Prof. M. Pérol
- Unité d'Oncologie Thoracique, CHU Larrey /Oncopôle, Toulouse, supervised by Prof. J. Mazières.
Some secondary centres, nearby the three principal mentioned above, will be associated to ensure recruitment of patients, in accordance to provisional planning.
- The primary objective is to validate the existence and distribution of the hypothetical immune profile (within blood and tumoral tissue) explaining primary or adaptive resistance to standard PD-1 inhibitors monotherapy, in NSCLC patients.
- The secondary objectives are to better characterize :
- PK/PD relationships,
- inter-patient PK variability,
- If systemic exposure levels could be predictive of efficacy of PD-1 ICI, in NSCLC patients.
- Some exploratory objectives are :
- to assess a predictive value of a panel of endothelial biomarkers, in NSCLC patients.
- to compare predictive immune \& endothelial biomarker profiles with those of sensitive tumors.
- to better understand which profiles track significantly with progression following PD-1 ICI administration, in order to improve advanced NSCLC patients' stratification, for future clinical trials.
Detailed description
Visits will match with usual schedule of patient's appointments with their referent oncologist or for injections of ICIs, when blood sampling or biopsies will be done. Feces will be collected by patients themselves, at home (optional).
The same day of registration for either an EMA approved first line PD-1 or PD-L1 inhibitor in combination with platinum-based chemotherapy OR a standard 2nd or 3rd line PD-(L) 1 ICIs monotherapy (to date, Nivolumab, Pembrolizumab, Atezolizumab), 450 advanced NSCLC patients will undergo a screening visit (Vs). If they are eligible, after signing an informed written consent, they will be blood-sampled specifically for the study:
- after 3 or 4 weeks (V1-1st assessment of PK/PD, after the 2d course),
- after 6 weeks (V2),
- after 8 or 9 weeks (V3-2nd assessment of PK/PD, after the last course),
- after 12 weeks of treatment (V4- samples for 3rd assessment of PK/PD and other analyses ).
- after 18 weeks (V5- samples for 4th assessment of PK/PD and other analyses,),
- after 24 weeks of treatment (V6-5th assessment of PK/PD and other analyses).
Patients will also be re-biopsied (primitive tumor or metastasis) specifically for the study, at V2. Referent patients'oncologist will opt for the simplest technical approach with a minimal risk exposure for patients. Standard procedures will be implemented for subsequent patient's monitoring.
Patients will also provide remaining samples from pre-treatment surgical resections/biopsies (primitive tumor or metastasis).
If they are amenable to collect feces samples at home, an auto collection kit will be supplied to them, before the first injection (Vs) and when they come for the 2nd course (i.e after 3 or 4 weeks post initiation) in order to self-collect feces within the week beforeV2 - 6 weeks post initiation).
Following the last study visit (V4 or V5 or V6)or at the time of a subsequent disease progression, patients will enter to the follow up period (a minimum 24 weeks ). They will be followed by their usual referent oncologist, no additional visit is required. Subsequent response to the anti-PD (L) 1 treatment, anti-cancer therapy, survival will be collected via patient medical records and analysed for current study.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NSCLC patients | Experimental | Procedure: BIOPSY, Diagnostic Test: blood-sampled, Other: feces samples |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- - Patients must be over 18 years
- Patients must have histologically confirmed diagnosis of advanced (proven stade IV) or recurrent NSCLC,
- Their ECOG Performance Status must be of 0 or 1
- EITHER patients must be previously untreated and eligible for an EMA approved first line PD-1 or PD-L1 inhibitor in combination with platinum-based chemotherapy, irrespective of their tumor histology
- These EMA approved first line combinations must be reimbursed by French Health Insurance or at least, must have an Authorization for Temporary Use (ATU) in France
Key exclusion criteria (16 listed)
- Patients previously untreated and eligible for a first line PD-1 or PD-L1 inhibitor in monotherapy
- Combination of PD-1 or PD-L1 inhibitor with bevacizumab
- Exclusive bone progression
- Exclusive cerebral progression not amenable to surgical biopsy
- Absence of a target lesion according to RECIST criteria 1.1
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 |
|---|---|---|
| BIOPSYre-biopsy (primitive tumor or metastasis) specifically for the study, at V2(6 weeks) | Procedure or surgery | NSCLC patients |
| blood-sampled* after 3 or 4 weeks (V1-1st assessment of PK/PD, after the 2d course), * after 6 weeks (V2), * after 8 or 9 weeks (V3-2nd assessment of PK/PD, after the last course), * - after 12 weeks of treatment (V4- samples for 3rd assessment of PK/PD and other analyses ). * after 18 weeks (V5- samples for 4th assessment of PK/PD and other analyses,), * after 24 weeks of treatment (V6-5th assessment of PK/PD and other analyses). | Diagnostic test | NSCLC patients |
| feces samplesIf they are amenable to collect feces samples at home, an auto collection kit will be supplied to them, before the first injection (Vs) and when they come for the 2nd course (i.e after 3 or 4 weeks post initiation) in order to self-collect feces within the week beforeV2 - 6 weeks post initiation). | Other | NSCLC patients |
Primary outcome
Immuno-monitoring
Time frame: 54 MONTHS
BLOOD SAMPLES to characterize B, T, NK, and dendritic cell subsets and monocyte populations as well as Innate Lymphoid Cells (ILC) with cytometry analysis
6 secondary outcomes
Measure the number of somatic mutations
Time frame: 54 MONTHS
Measure the number of somatic mutations
Time frame: 54 MONTHS
measure the Circulating endothelial cells (CECs)
Time frame: 54 MONTHS
Minimum Plasma Concentration Cmin of anti PD (L) 1 treatment
Time frame: 54 MONTHS
Maximum Plasma Concentration Cmax of anti PD (L) 1 treatment
Time frame: 54 MONTHS
lymphocytes DNA extraction's
Time frame: 54 MONTHS
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2023.
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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.
François CREMIEUX study director
ASSISTANCE PUBLIQUE HOPITAUX D EMARSEILLE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BIOPSY, blood-sampled and feces samples in people with Non-small Cell Lung Cancer Patients, run by Assistance Publique Hopitaux De Marseille 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 11 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 26 Jun 2023. 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?
Results are not available in the source record.
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?
Immuno-monitoring (time frame: 54 MONTHS). 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 26 Jun 2023.