xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05973344</url>
    </required_header>
    <id_info>
      <org_study_id>29BRC22.0189 (TADIG-P)</org_study_id>
      <secondary_id>2022-A02237-36</secondary_id>
      <nct_id>NCT05973344</nct_id>
    </id_info>
    <brief_title>Understanding and Anticipating Therapeutic and ADverse Responses in Anti-cancer Immune Checkpoint Inhibition Towards a Better Therapeutic Management of Patients</brief_title>
    <acronym>TADIG-P</acronym>
    <official_title>Understanding and Anticipating Therapeutic and ADverse Responses in Anti-cancer Immune Checkpoint Inhibition Towards a Better Therapeutic Management of Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Brest</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital, Brest</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this observational study is to explore the value of blood biomarkers for the&#xD;
        purpose of predicting irAE development in cancer patients treated with immune checkpoint&#xD;
        inihibitors (ICI) alone or in combination with other treatments (chemotherapy, radiotherapy&#xD;
        and targeted therapy).&#xD;
  &#xD;
        Data and blood samples will be collected from participants at different time points as part&#xD;
        of routine follow-up visits. Data and blood samples will be analysed. Analysis will include&#xD;
        the characterization of immune cells by mass and flow cytometry.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Advances in treating patients with immunotherapy have dramatically changed cancer morbidity&#xD;
        and mortality. Immune checkpoint inhibitors (ICI), alone or combined with other treatments,&#xD;
        are currently used both as standard of care or in experimental settings for various cancers.&#xD;
        ICI treatment induces objective clinical responses in 20-40% of patients (varies by tumor&#xD;
        type); however, this leaves a majority of patients that do not respond to ICI therapy. ICI&#xD;
        drugs purposely release immune regulatory controls and consequently increase immune&#xD;
        activities; however, this release also provokes a significant risk of immunerelated adverse&#xD;
        events (irAEs) such as dermatitis, hepatitis, thyroiditis and colitis, and less frequently&#xD;
        but clinically important, hypophysitis, myocarditis and pneumonia. While the incidence of&#xD;
        irAE is highly variable and influenced by many factors, Phase I and II trials reported rates&#xD;
        from 10% to 80% for any grade irAE while an irAE of grade 3 or higher was observed in 2.5% to&#xD;
        18% of subjects. Recently, Jing et al. demonstrated that 20% of patients receiving&#xD;
        anti-PD-1/PD-L1 had at least one irAE by integrating real-world pharmacovigilance of 26 tumor&#xD;
        types for a total of 18,706 patients. Presently, the specific immune mechanism(s) driving&#xD;
        irAE are unknown and biomarkers that predict their onset, particularly high-grade irAE, are&#xD;
        urgently needed. For this reason, we hypothesize that an in-depth characterization and&#xD;
        comparisons of the cell subpopulations composing and interacting within the primary cancer&#xD;
        lesions, the peripheral blood, and in the organs in which irAE arise could help to better&#xD;
        understand but also predict the clinical therapeutic response or/and irAE in patients with&#xD;
        advanced cancers treated with ICI.&#xD;
  &#xD;
        The research is a non-interventional monocentric prospective study of humans for the&#xD;
        development of biological and medical knowledge, in which the procedures are performed and&#xD;
        the products used in the usual manner, without additional or unusual diagnostic, treatment or&#xD;
        monitoring procedures. The study includes patients monitored for their cancer at CHU of Brest&#xD;
        and treated using Immune Checkpoint Inhibitors. Data and peripheral blood (47mL) will be&#xD;
        collected at different time points as part of routine follow-up visits for analysis. Analysis&#xD;
        will include the characterization of immune cells by mass and flow cytometry.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2028</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Occurrence of irAE over the duration of the patient's follow-up</measure>
      <time_frame>36 months</time_frame>
      <description>Apparition of irAE is appreciated according the physician definition. The description and grading scales of irAE found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Survival (PFS).</measure>
      <time_frame>36 months</time_frame>
      <description>PFS is defined as the time from random assignment in the clinical trial to disease progression or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Survival (OS).</measure>
      <time_frame>36 months</time_frame>
      <description>OS is defined as the time from random assignment in the clinical trial to death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tumor response according to the iRECIST criteria</measure>
      <time_frame>36 months</time_frame>
      <description>A copy of the iRECIST can be downloaded from the Lancet Oncology web site: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30074-8/fulltext</description>
    </secondary_outcome>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Cancer</condition>
    <eligibility>
      <study_pop>
        <textblock>
          All patients with tumors treated with ICI (anti-CTLA-4, anti-PD-1/PD-L1, LAG3, etc.) as&#xD;
          standard-of-care, alone or in combination with other treatments (chemotherapy, radiotherapy&#xD;
          and targeted therapy)&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          -  Age ≥ 18 years old&#xD;
  &#xD;
            -  ECOG performance status ≤ 1&#xD;
  &#xD;
            -  Must have histologically or cytologically confirmed tumour, eligible for treatment&#xD;
               with ICI as standard-of-care alone or in combination with another ICI, ICI with&#xD;
               chemotherapy, ICI with radiotherapy, or ICI with targeted therapy with no restrictions&#xD;
               on number of prior systemic therapies&#xD;
  &#xD;
            -  Adequate bone marrow function as defined below&#xD;
  &#xD;
                 -  Absolute neutrophil count ≥ 1500/µL or 1.5x109/L&#xD;
  &#xD;
                 -  Hemoglobin ≥ 9 g/dL&#xD;
  &#xD;
                 -  Platelets ≥ 100000/µL or 100x109/L&#xD;
  &#xD;
            -  Adequate liver function as defined below&#xD;
  &#xD;
                 -  Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome &lt; 3xUNL is&#xD;
                    allowed&#xD;
  &#xD;
                 -  AST (SGOT)/ALT (SGPT) ≤ 3.0 x ULN&#xD;
  &#xD;
                 -  Alkaline phosphatase ≤ 3.3 x ULN&#xD;
  &#xD;
            -  Adequate renal function as defined below&#xD;
  &#xD;
               _- Creatinine ≤ 1.5 x UNL or creatinine clearance &gt; 60 mL/min&#xD;
  &#xD;
            -  Patient monitored for their cancer at CHU of Brest&#xD;
  &#xD;
            -  Did not oppose for their samples and clinical data to be used for translational&#xD;
               research&#xD;
  &#xD;
            -  Non-opposition form obtained prior to any study related procedure&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patient with a significant medical, neuro-psychiatric, or surgical condition,&#xD;
               currently uncontrolled by treatment, which, in the principal investigator's opinion,&#xD;
               may interfere with completion of the study&#xD;
  &#xD;
            -  Patient already receiving ICI&#xD;
  &#xD;
            -  Primary immunodeficiency and/or history of allogenic transplantation&#xD;
  &#xD;
            -  Current active infection&#xD;
  &#xD;
            -  Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C&#xD;
               Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection)&#xD;
  &#xD;
            -  Subject of guardianship (tutorship, curatorship)&#xD;
  &#xD;
            -  Active pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Benjamin Auberger</last_name>
      <role>Principal Investigator</role>
      <affiliation>CHU Brest</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Benjamin Auberger</last_name>
      <phone>+33298223740</phone>
      <email>benjamin.auberger@chu-brest.fr</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>immunotherapy</keyword>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05973344
  org study id: 29BRC22.0189 (TADIG-P)
  secondary id: 2022-A02237-36
  nct id: NCT05973344
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this observational study is to explore the value of blood biomarkers for the
        purpose of predicting irAE development in cancer patients treated with immune checkpoint
        inihibitors (ICI) alone or in combination with other treatments (chemotherapy, radiotherapy
        and targeted therapy).
  
        Data and blood samples will be collected from participants at different time points as part
        of routine follow-up visits. Data and blood samples will be analysed. Analysis will include
        the characterization of immune cells by mass and flow cytometry.
  Advances in treating patients with immunotherapy have dramatically changed cancer morbidity
        and mortality. Immune checkpoint inhibitors (ICI), alone or combined with other treatments,
        are currently used both as standard of care or in experimental settings for various cancers.
        ICI treatment induces objective clinical responses in 20-40% of patients (varies by tumor
        type); however, this leaves a majority of patients that do not respond to ICI therapy. ICI
        drugs purposely release immune regulatory controls and consequently increase immune
        activities; however, this release also provokes a significant risk of immunerelated adverse
        events (irAEs) such as dermatitis, hepatitis, thyroiditis and colitis, and less frequently
        but clinically important, hypophysitis, myocarditis and pneumonia. While the incidence of
        irAE is highly variable and influenced by many factors, Phase I and II trials reported rates
        from 10% to 80% for any grade irAE while an irAE of grade 3 or higher was observed in 2.5% to
        18% of subjects. Recently, Jing et al. demonstrated that 20% of patients receiving
        anti-PD-1/PD-L1 had at least one irAE by integrating real-world pharmacovigilance of 26 tumor
        types for a total of 18,706 patients. Presently, the specific immune mechanism(s) driving
        irAE are unknown and biomarkers that predict their onset, particularly high-grade irAE, are
        urgently needed. For this reason, we hypothesize that an in-depth characterization and
        comparisons of the cell subpopulations composing and interacting within the primary cancer
        lesions, the peripheral blood, and in the organs in which irAE arise could help to better
        understand but also predict the clinical therapeutic response or/and irAE in patients with
        advanced cancers treated with ICI.
  
        The research is a non-interventional monocentric prospective study of humans for the
        development of biological and medical knowledge, in which the procedures are performed and
        the products used in the usual manner, without additional or unusual diagnostic, treatment or
        monitoring procedures. The study includes patients monitored for their cancer at CHU of Brest
        and treated using Immune Checkpoint Inhibitors. Data and peripheral blood (47mL) will be
        collected at different time points as part of routine follow-up visits for analysis. Analysis
        will include the characterization of immune cells by mass and flow cytometry.
  observational model: Cohort
  time perspective: Prospective
  measure: Occurrence of irAE over the duration of the patient's follow-up
  time frame: 36 months
  description: Apparition of irAE is appreciated according the physician definition. The description and grading scales of irAE found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.
  measure: Survival (PFS).
  time frame: 36 months
  description: PFS is defined as the time from random assignment in the clinical trial to disease progression or death from any cause.
  measure: Survival (OS).
  time frame: 36 months
  description: OS is defined as the time from random assignment in the clinical trial to death.
  measure: Tumor response according to the iRECIST criteria
  time frame: 36 months
  description: A copy of the iRECIST can be downloaded from the Lancet Oncology web site: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30074-8/fulltext
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Benjamin Auberger
  role: Principal Investigator
  affiliation: CHU Brest
  last name: Benjamin Auberger
  phone: +33298223740
  email: benjamin.auberger@chu-brest.fr
  responsible party type: Sponsor