Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT03493581
Recruitment Status : Recruiting
First Posted : April 10, 2018
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille

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:

  • Centre d'Essais Précoces en Cancérologie de Marseille (CEPCM)-Unité de Phase I Oncologie labélisée CLIP² in APHM, Marseille, supervised by Prof. F. Barlesi
  • 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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Patients Procedure: BIOPSY Diagnostic Test: blood-sampled Other: feces samples Not Applicable

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 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),
  • and after 12 weeks of treatment (V4). 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 after the 2nd (V2 - 6 weeks or V3- 8 weeks), depending on courses timelines.

Following the last study visit (V4), patients will enter to the follow up period (a maximum 2 years period). 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)
Actual Study Start Date : March 8, 2018
Estimated Primary Completion Date : March 8, 2022
Estimated Study Completion Date : August 12, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NSCLC patients Procedure: BIOPSY
re-biopsy (primitive tumor or metastasis) specifically for the study, at V2(6 weeks)

Diagnostic Test: 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),
  • and after 12 weeks of treatment (V4).

Other: feces samples
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 after the 2nd (V2 - 6 weeks or V3- 8 weeks), depending on courses timelines.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Measure the number of somatic mutations [ Time Frame: 54 MONTHS ]
    BLOOD SAMPLES- extraction of nucleic acids from Plasma

  2. Measure the number of somatic mutations [ Time Frame: 54 MONTHS ]
    Tumor tissues- extraction of nucleic acids

  3. measure the Circulating endothelial cells (CECs) [ Time Frame: 54 MONTHS ]
    BLOOD SAMPLES using a CD146-based immunomagnetic separation assay.

  4. Minimum Plasma Concentration Cmin of anti PD (L) 1 treatment [ Time Frame: 54 MONTHS ]
    BLOOD SAMPLES

  5. Maximum Plasma Concentration Cmax of anti PD (L) 1 treatment [ Time Frame: 54 MONTHS ]
    BLOOD SAMPLES

  6. lymphocytes DNA extraction's [ Time Frame: 54 MONTHS ]
    Relevant polymorphisms will be screened by NGS technology



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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)
  • Patients 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 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:

  • 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

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 ClinicalTrials.gov identifier (NCT number): NCT03493581


Contacts
Layout table for location contacts
Contact: FABRICE BARLESI +33 (0)4 91 38 56 28 fabrice.barlesi@ap-hm.fr

Locations
Layout table for location information
France
Assistance Pubique Hopitaux de Marseille Recruiting
Marseille, France, 13354
Contact    Tel. +33.(0) 4 91 38 27 47    drci@ap-hm.fr   
Principal Investigator: Fabrice BARLESI         
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
Layout table for investigator information
Study Director: jean-olivier ARNAUD ASSISTANCE PUBLIQUE HOPITAUX D EMARSEILLE
Layout table for additonal information
Responsible Party: Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier: NCT03493581    
Other Study ID Numbers: 2017-67
2018-A03518-45 ( Other Identifier: IDRCB )
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: June 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms