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Integrated Discovery of New Immuno-Molecular Actionable Biomarkers for Tumors With Immune-suppressed Environment (IDeATIon)

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ClinicalTrials.gov Identifier: NCT03706625
Recruitment Status : Recruiting
First Posted : October 16, 2018
Last Update Posted : June 19, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
The explosion of novel therapies targeting tumor mutations or immune molecules requests to define or better characterize the mutational profiles of tumors that are none or insufficiently explored so far. This is particularly the case for tumors arising in immune-suppressed individuals or environments which have been poorly, if any, analyzed so far with modern molecular methods. The goal of the translational research program, Ideation, is to define novel biomarkers such as the tumor mutational profiling and immunomutanome in such contexts and to compare the results obtained to those observed in immune competent individuals. In addition, this approach will allow to characterize novel key non-invasive diagnostic and prognostic biomarkers such as circulating tumoral DNA and cells. Altogether results will provide novel biomarkers to better adapt therapeutic strategies in these cancers, to monitor response to treatment as well as to define new molecular targets of potential therapeutic strategies.

Condition or disease
Non Hodgkin Lymphoma Non Small Cell Lung Cancer Glioma

Detailed Description:
The main objective is to discover novel invasive and non-invasive immuno-molecular actionable biomarkers in rare but severe tumors arising in immune-suppressed compared for some tumors in immune-competent patients. Indeed, this tumors present a deficient immune environment, either due to the host acquired immune deficiency, i.e. transplantations or HIV infection, or because the diseased tissue belongs in an immune sanctuary as the brain. The primary hypothesis, in this context, is that these tumor mutational profiles and their changes during drug therapy must be influenced by the immune environment and response. This must lead to differences from similar tumors observed in immune-competent environments (immunocompetent individuals or tissues expressing immunity), responsible for: modification in the molecular targets for appropriate drugs ; alteration of tumor immunogenicity and of future immune-based therapies ; specific biomarkers for monitoring the response to drug therapy. The objectives of this program are to carry on invasive and non-invasive investigations in order to define the mutational profile of these free types of severe tumors, non-Hodgkin lymphoma (NHL), lung cancers and gliomas arising in hosts or tissues with altered immunity. These investigations will lead to : identify novel invasive and non-invasive biomarkers for predicting and evaluating efficacy of future personalized and immune-based therapies; compare tumors from immune-suppressed and immune-competent hosts; discover hot spots of tumoral mutations as mechanisms of tumors resistance, new molecular targets for future molecular and immune-bases therapeutic strategies; define the tumor immunomutanome as a score of neo-epitopes predicting: tumor immunogenicity, disease outcome and efficacy of immunotherapies; detect non-invasive tumoral biomarkers from liquid biopsies based on Circulating tumoral DNA and Circulating tumoral Cells to facilitate future diagnosis and monitoring of such tumors; identify biomarkers of tumor escape or resistance to treatments.

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Study Type : Observational
Estimated Enrollment : 170 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Integrated Discovery of New Immuno-Molecular Actionable Biomarkers for Tumors With Immune-suppressed Environment
Actual Study Start Date : November 20, 2018
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Group/Cohort
Non-Hodgkin-Lymphoma (after transplantation)
Immune-suppressed patients suffering from Non-Hodgkin-Lymphoma (after transplantation) and followed in the four centers of reference for rare cancers (KVirogref, CANCERVIH, LOC and POLA)
Non-small cell lung cancer
Immune-suppressed patients suffering from HIV-related non-small cell lung cancer, followed in the four centers of reference for rare cancers (KVirogref, CANCERVIH, LOC and POLA)
Primary Central Nervous System Lymphoma
Patients suffering from primitive cerebral lymphomas and followed in the four centers of reference for rare cancers (KVirogref, CANCERVIH, LOC and POLA)
Gliomas
Patients suffering from Gliomas and followed in the four centers of reference for rare cancers (KVirogref, CANCERVIH, LOC and POLA)
Non-Hodgkin-Lymphoma with HIV infection
Immune-suppressed patients (during HIV infection) and followed in the four centers of reference for rare cancers (KVirogref, CANCERVIH, LOC and POLA)



Primary Outcome Measures :
  1. Prognostic value of the tumor invasive biomarkers [ Time Frame: at Day 0 ]
    Analyze of the tumor biomarkers on frozen biopsy for the three types of cancer (NHL, lung cancer and glioma)


Secondary Outcome Measures :
  1. Determination of tumoral biomarkers [ Time Frame: at Day 0 ]
    i) the mutational tumor profile by using a next generation sequencing (NGS) comparingson of the tumor DNAgenome with the patient's constitutional genome (sequenced on blood or saliva) for the three types of cancer (NHL, lung cancer and glioma) and ii) immunomutanome and score of neo-epitopes defined by tumor RNA-sequencing defining the specific mutants expressed in the tumor and able to be recognized by the immune system.

  2. Prognostic value of the tumor non invasive biomarkers [ Time Frame: at Day 0, Month 3 and Month 6 ]
    The analysis of circulating DNA (ctDNA) will be performed from plasma collected from the prospective cohort of the patients for the three types of cancer (NHL, lung cancer and glioma). DNA will be extracted and amplified followed by Next-Generation Sequencing (NGS) and Droplet digital PCR (ddPCR) analysis for the identification of new biomarkers and/or for the follow up of mutations previously identified on tumor DNA. Results will be compared to tissue results in each group and to CTCs results in the Lung cancer group and prognostic values of these biomarkers will be assessed from clinical datas.

  3. Prognostic value of the tumor non-invasive biomarkers [ Time Frame: at Day 0, Month 3 and Month 6 ]
    The analysis of circulating tumor cells (CTCs) will be performed from whole peripheral blood collected from the prospective cohort of patients with lung cancer infected or not with HIV. CTC fraction will be prepared from a cell size-based enrichment protocol. NextThen, DNA and RNA will be extracted and amplified followed by Next-Generation Sequencing (NGS) and RNA sequencing for the identification of new biomarkers. Droplet digital PCR (ddPCR) analysis will also be performed for validation and patient follow-up. Mutations and expression data in CTC will be compared to tissue and ctDNA in the two groups and prognostic values of these biomarkers will be assessed from clinical datas.


Biospecimen Retention:   Samples With DNA
Blood, saliva, biopsy samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients followed-up at Pitié-Salpêtrière hospital or Tenon hospital with histological diagnosis of HIV-related non-small cell lung cancer, HIV-related Non-Hodgkin-Lymphomas (NHL), post-transplant NHL, primary lymphoma of the central nervous system, glioma.
Criteria

Inclusion Criteria:

  • Age ≥ 18 years.
  • Followed at Pitié-Salpêtrière or Tenon Hospitals.
  • Histological diagnosis confirmed of:

    • Non-small cell lung cancer (adenocarcinoma, squamous cell, large cells) related to HIV, or
    • Non-Hodgkin's lymphoma (NHL): HIV-related NHL, post-transplant LNH (LPT) according to WHO (World Health Organization) 2016 classification, primary CNS (central nervous system) lymphoma (LPS), or
    • Glioma
  • Naïve cancer treatment.
  • Cancer undergoing surgery for excision or a large biopsy (pleural biopsy under video-thoracoscopy, mediastinoscopy, biopsy lymph node excision or cutaneous or cerebral metastasis).
  • For patients with NSCLC: hemoglobin level> 9 g / dL; for patients with NHL or glioma: hemoglobin > 7 g / dL.
  • Weight ≥ 48 kg.
  • Informed consent to participation signed before carrying out any specific procedure of the study.
  • Affiliation to the French social security system.

Exclusion Criteria:

  • Other cancer than those in the study:

    • For NHL after transplantation: marginal zone NHL, follicular NHL, mantle cell NHL, lymphoplasmocytic NHL (non-WHO lymphoma as LPT)
    • For HIV-related LPTs and NHLs: LPS
    • For LPT: tumor EBV status unknown
    • For lung cancers: small cell lung cancer
  • Absence of tumor material, blood or saliva samples taken before the start of chemotherapy
  • Major under guardianship or curatorship

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): NCT03706625


Contacts
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Contact: Jean-Philippe SPANO, MD, PhD (0)142160497 ext 0033 jean-philippe.spano@aphp.fr
Contact: Brigitte AUTRAN, MD, PhD (0)1.42.17.74.03 ext 0033 brigitte.autran-ext@aphp.fr

Locations
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France
Groupe Hospitalier Pitié-Salpêtrière Recruiting
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Study Chair: Jean-Philippe SPANO, MD, PhD Pitié-Salpêtrière hospital (APHP)
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03706625    
Other Study ID Numbers: NI18022J
2018-A01099-46 ( Other Identifier: IDRCB )
First Posted: October 16, 2018    Key Record Dates
Last Update Posted: June 19, 2020
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Non Hodgkin Lymphoma
glioma
lung cancer
HIV
transplantation
brain
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Glioma
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue