search
Back to results

Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling) (PIONeeR)

Primary Purpose

Non-small Cell Lung Cancer Patients

Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
BIOPSY
blood-sampled
feces samples
Sponsored by
Assistance Publique Hopitaux De Marseille
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Non-small Cell Lung Cancer Patients

Eligibility Criteria

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

Inclusion Criteria:

  • - 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)
  • 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

Exclusion Criteria:

  • 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
  • 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

Sites / Locations

  • Assistance Pubique Hopitaux de Marseille

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NSCLC patients

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Measure the number of somatic mutations
BLOOD SAMPLES- extraction of nucleic acids from Plasma
Measure the number of somatic mutations
Tumor tissues- extraction of nucleic acids
measure the Circulating endothelial cells (CECs)
BLOOD SAMPLES using a CD146-based immunomagnetic separation assay.
Minimum Plasma Concentration Cmin of anti PD (L) 1 treatment
BLOOD SAMPLES
Maximum Plasma Concentration Cmax of anti PD (L) 1 treatment
BLOOD SAMPLES
lymphocytes DNA extraction's
Relevant polymorphisms will be screened by NGS technology

Full Information

First Posted
March 20, 2018
Last Updated
June 22, 2023
Sponsor
Assistance Publique Hopitaux De Marseille
search

1. Study Identification

Unique Protocol Identification Number
NCT03493581
Brief Title
Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)
Acronym
PIONeeR
Official Title
Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 8, 2018 (Actual)
Primary Completion Date
March 8, 2024 (Anticipated)
Study Completion Date
August 12, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique Hopitaux De Marseille

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer Patients

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
450 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NSCLC patients
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
BIOPSY
Intervention Description
re-biopsy (primitive tumor or metastasis) specifically for the study, at V2(6 weeks)
Intervention Type
Diagnostic Test
Intervention Name(s)
blood-sampled
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
feces samples
Intervention Description
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).
Primary Outcome Measure Information:
Title
Immuno-monitoring
Description
BLOOD SAMPLES to characterize B, T, NK, and dendritic cell subsets and monocyte populations as well as Innate Lymphoid Cells (ILC) with cytometry analysis
Time Frame
54 MONTHS
Secondary Outcome Measure Information:
Title
Measure the number of somatic mutations
Description
BLOOD SAMPLES- extraction of nucleic acids from Plasma
Time Frame
54 MONTHS
Title
Measure the number of somatic mutations
Description
Tumor tissues- extraction of nucleic acids
Time Frame
54 MONTHS
Title
measure the Circulating endothelial cells (CECs)
Description
BLOOD SAMPLES using a CD146-based immunomagnetic separation assay.
Time Frame
54 MONTHS
Title
Minimum Plasma Concentration Cmin of anti PD (L) 1 treatment
Description
BLOOD SAMPLES
Time Frame
54 MONTHS
Title
Maximum Plasma Concentration Cmax of anti PD (L) 1 treatment
Description
BLOOD SAMPLES
Time Frame
54 MONTHS
Title
lymphocytes DNA extraction's
Description
Relevant polymorphisms will be screened by NGS technology
Time Frame
54 MONTHS

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - 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) 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 Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
François CREMIEUX
Organizational Affiliation
ASSISTANCE PUBLIQUE HOPITAUX D EMARSEILLE
Official's Role
Study Director
Facility Information:
Facility Name
Assistance Pubique Hopitaux de Marseille
City
Marseille
ZIP/Postal Code
13354
Country
France

12. IPD Sharing Statement

Learn more about this trial

Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)

We'll reach out to this number within 24 hrs