<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/NCT03791073</url>
  </required_header>
  <id_info>
    <org_study_id>RECHMPL18_0437</org_study_id>
    <nct_id>NCT03791073</nct_id>
  </id_info>
  <brief_title>New Biomarkers in Pancreatic Cancer Using EXPEL Concept</brief_title>
  <acronym>PANEXPEL</acronym>
  <official_title>Discovery of New Biomarkers in Pancreatic Cancer Using Novel Nondestructive OMICS Methodology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>IRCM U1194 INSERM, Tumor Microenvironment and Resistance to Treatment Lab</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>IRCM U1194 INSERM, Cancer Bioinformatics and Systems Biology's team</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Montpellier</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 investigators recently engineered a novel biomarker discovery approach that is&#xD;
      non-destructive and fully compatible with OMICS profiling as well as routine clinical&#xD;
      procedures (5). The latter approach - termed EXPEL - mines the interstitial tissue fluid that&#xD;
      is the richest source of soluble, undiluted and uncontaminated biomarkers. The method notably&#xD;
      gives access to proteins, metabolites, RNA, DNA and exosomes, thus enabling holistic&#xD;
      biomarker discovery. Owing to its non-destructive nature, EXPEL provides for the first time&#xD;
      both clinicians and researchers with the opportunity to analyze identical material.&#xD;
&#xD;
      The investigators hypothesize that the conservation liquid used to collect cells and biopsy&#xD;
      after endoscopic ultrasound for pancreatic biopsy could contain the tissue secretome and&#xD;
      permit a comprehensive OMICS analysis of PDAC (all stages confounded) by using a &quot;modified&#xD;
      EXPEL&quot; procedure. These are ideal conditions for EXPEL approach that will additionally to&#xD;
      finding novel biomarkers also shed light on complex network of cancer cell-stroma&#xD;
      interactions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Biomarkers that are readily detectable in fluid biopsies are of outmost importance for&#xD;
      diagnosis and prediction of therapeutic response in all cancer patients. Pancreatic ductal&#xD;
      adenocarcinoma (PDAC) is an example of a deadly malignancy that is diagnosed very late due to&#xD;
      lack of sensitive and reliable markers [1]. The incidence and mortality of PDAC will double&#xD;
      in the next 15 years, which is unprecedented among all cancer types [2]. Secondary cancer&#xD;
      prevention through early diagnosis of PDAC will therefore be an essential preparedness asset&#xD;
      for facing the immense healthcare burden.&#xD;
&#xD;
      Discovery of diagnostic biomarkers depends essentially on the availability of patient&#xD;
      material ideally collected at different time points during the disease progression (e.g.&#xD;
      early lesion, before treatment and after recurrence). Unfortunately, it is very difficult to&#xD;
      access fresh biopsies from pre-malignant lesions for research purposes. These are needed in&#xD;
      their entirety for histo-pathological evaluation and diagnosis. The ability to use liquid&#xD;
      biopsies (e.g. serum, urine, saliva) brought the promise to circumvent this problem, opening&#xD;
      access to many different biomolecules such as circulating DNA and proteins. However, upon&#xD;
      their release from the tumor, these molecules are diluted up to several billion-fold in blood&#xD;
      with molecular species originating from healthy tissues [3-4]. This hampers de novo discovery&#xD;
      of biomarkers for diagnosing and understanding the disease.&#xD;
&#xD;
      To circumvent these limitations, the investigators recently engineered a novel biomarker&#xD;
      discovery approach that is non-destructive and fully compatible with OMICS profiling as well&#xD;
      as routine clinical procedures (5). The latter approach - termed EXPEL - mines the&#xD;
      interstitial tissue fluid that is the richest source of soluble, undiluted and uncontaminated&#xD;
      biomarkers. The method notably gives access to proteins, metabolites, RNA, DNA and exosomes,&#xD;
      thus enabling holistic biomarker discovery. Owing to its non-destructive nature, EXPEL&#xD;
      provides for the first time both clinicians and researchers with the opportunity to analyze&#xD;
      identical material, while having virtually no disadvantage in their respective tasks. The&#xD;
      investigators have recently shown the ability of our methodology to find new markers in the&#xD;
      context of precious human colorectal cancer samples. Thus, the investigators are convinced&#xD;
      that EXPEL can be successfully applied to pancreatic cancer. In addition, knowing the&#xD;
      important proportion of stroma in PDAC (usually 2/3 of tumor mass), the secretome of&#xD;
      pancreatic cancer is expected to be much richer in soluble &quot;communication factors&quot; exchanged&#xD;
      between cancer cells and host tissue.&#xD;
&#xD;
      In clinical practice, most of patients undergo endoscopic ultrasound with fine needle&#xD;
      aspiration/biopsy of the pancreatic mass to confirm the diagnosis of PDAC. The needle is&#xD;
      rinsed in a conservation liquid Cytolyt® (Methanol 30% et water 50%) and sent to the&#xD;
      pathologists. Microbiopsy are fixed in paraffin then analyzed and liquid is cytofiltrated to&#xD;
      keep potential tumor cells. The remnant Cytolyt® liquid is systematically trashed.&#xD;
&#xD;
      The present study is based on the hypothesis that this liquid, previously in contact with&#xD;
      tumoral tissue, could contain the tissue secretome and permit a comprehensive OMICS analysis&#xD;
      of PDAC (all stages confounded) by using a &quot;modified EXPEL&quot; procedure. These are ideal&#xD;
      conditions for EXPEL approach that will additionally to finding novel biomarkers also shed&#xD;
      light on complex network of cancer cell - stroma interactions.&#xD;
&#xD;
      For this purpose, the investigators aim to perform proteomic analysis on the conservation&#xD;
      liquid (Cytolyt) in patients who underwent endoscopic ultrasound with fine needle&#xD;
      aspiration/biopsy for suspicious pancreatic mass at the CHU de Montpellier between Jan 2018&#xD;
      and Jan 2019.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">November 1, 2024</completion_date>
  <primary_completion_date type="Actual">January 1, 2019</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Predictive value of each protein contained in Cytolyt® for the positive diagnosis of pancreatic ductal adenocarcinoma</measure>
    <time_frame>an average of 1 year</time_frame>
    <description>Correlation with positive diagnosis of pancreatic ductal adenocarcinoma and proteins quantity in Cytolyt® samples using ROC curves (sensibility/specificity: Area Under the Curve &gt; 0.85) and binary logistic regression method with controlling for the effects of the co-variates (such as age, disease cTNM stage, and treatment details).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis</measure>
    <time_frame>1 year</time_frame>
    <description>Disease-free survival (percentage of patients without recurrence) at 1 year</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis</measure>
    <time_frame>1 year</time_frame>
    <description>Overall survival at 1 year (percentage of patients alive)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis</measure>
    <time_frame>1 year</time_frame>
    <description>Disease-free survival (DFS) (time from diagnosis to time of first radiological evidence of local, regional, or distant relapse, or death due to any cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis</measure>
    <time_frame>1 year</time_frame>
    <description>Overall survival (OS) (time from diagnosis until death, regardless of cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis</measure>
    <time_frame>1 year</time_frame>
    <description>Kaplan Meier analysis, logrank test and Cox's proportional hazards regression model to identify biomarkers that are prognostically significant (Hazard ratio (HR) and its 95% confidence interval (CI)).</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Oncology</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Cytolyt Samples:&#xD;
&#xD;
      Liquid conservation samples from patients who underwent endoscopic ultrasound with fine&#xD;
      needle aspiration/biopsy for suspicious pancreatic mass at the CHU de Montpellier were&#xD;
      conserved at +4°c.&#xD;
&#xD;
      Cytolyt samples do not contain any cell or tissue from patient, this liquid is systematically&#xD;
      trashed in current practice. No genetics analysis will be performed from these particular&#xD;
      samples in the present study.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patient with pancreatic mass and suspicion of pancreatic ductal adenocarcinoma requiring&#xD;
        endoscopic ultrasound with fine needle biopsy or surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient with pancreatic mass and suspicion of pancreatic ductal adenocarcinoma&#xD;
             requiring endoscopic ultrasound with fine needle biopsy or surgery&#xD;
&#xD;
          -  Patient ≥18 years old&#xD;
&#xD;
          -  Patient naïve of any treatment of Pancreatic cancer&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient who reject the study protocol&#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>REGIS SOUCHE</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital, Montpellier</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>REGIS SOUCHE, MD</last_name>
    <phone>467337072</phone>
    <phone_ext>33</phone_ext>
    <email>fr-souche@chu-montpellier.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jean-Michel Fabre, MD, PhD</last_name>
    <phone>467337072</phone>
    <phone_ext>33</phone_ext>
    <email>jm-fabre@chu-montpellier.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Uhmontpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Regis SOUCHE, MD</last_name>
      <phone>467337072</phone>
      <phone_ext>33</phone_ext>
      <email>fr-souche@chu-montpellier.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Biomarker discovery</keyword>
  <keyword>Pancreatic adenocarcinoma</keyword>
  <keyword>Bioinformatics</keyword>
  <keyword>pancreatic cancer</keyword>
  <keyword>microenvironment</keyword>
  <keyword>proteomics</keyword>
  <keyword>transcriptomics</keyword>
  <keyword>metabolomics</keyword>
  <keyword>diagnosis</keyword>
  <keyword>Prognosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03791073
org study id: RECHMPL18_0437
nct id: NCT03791073
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators recently engineered a novel biomarker discovery approach that is
      non-destructive and fully compatible with OMICS profiling as well as routine clinical
      procedures (5). The latter approach - termed EXPEL - mines the interstitial tissue fluid that
      is the richest source of soluble, undiluted and uncontaminated biomarkers. The method notably
      gives access to proteins, metabolites, RNA, DNA and exosomes, thus enabling holistic
      biomarker discovery. Owing to its non-destructive nature, EXPEL provides for the first time
      both clinicians and researchers with the opportunity to analyze identical material.

      The investigators hypothesize that the conservation liquid used to collect cells and biopsy
      after endoscopic ultrasound for pancreatic biopsy could contain the tissue secretome and
      permit a comprehensive OMICS analysis of PDAC (all stages confounded) by using a "modified
      EXPEL" procedure. These are ideal conditions for EXPEL approach that will additionally to
      finding novel biomarkers also shed light on complex network of cancer cell-stroma
      interactions.
Biomarkers that are readily detectable in fluid biopsies are of outmost importance for
      diagnosis and prediction of therapeutic response in all cancer patients. Pancreatic ductal
      adenocarcinoma (PDAC) is an example of a deadly malignancy that is diagnosed very late due to
      lack of sensitive and reliable markers [1]. The incidence and mortality of PDAC will double
      in the next 15 years, which is unprecedented among all cancer types [2]. Secondary cancer
      prevention through early diagnosis of PDAC will therefore be an essential preparedness asset
      for facing the immense healthcare burden.

      Discovery of diagnostic biomarkers depends essentially on the availability of patient
      material ideally collected at different time points during the disease progression (e.g.
      early lesion, before treatment and after recurrence). Unfortunately, it is very difficult to
      access fresh biopsies from pre-malignant lesions for research purposes. These are needed in
      their entirety for histo-pathological evaluation and diagnosis. The ability to use liquid
      biopsies (e.g. serum, urine, saliva) brought the promise to circumvent this problem, opening
      access to many different biomolecules such as circulating DNA and proteins. However, upon
      their release from the tumor, these molecules are diluted up to several billion-fold in blood
      with molecular species originating from healthy tissues [3-4]. This hampers de novo discovery
      of biomarkers for diagnosing and understanding the disease.

      To circumvent these limitations, the investigators recently engineered a novel biomarker
      discovery approach that is non-destructive and fully compatible with OMICS profiling as well
      as routine clinical procedures (5). The latter approach - termed EXPEL - mines the
      interstitial tissue fluid that is the richest source of soluble, undiluted and uncontaminated
      biomarkers. The method notably gives access to proteins, metabolites, RNA, DNA and exosomes,
      thus enabling holistic biomarker discovery. Owing to its non-destructive nature, EXPEL
      provides for the first time both clinicians and researchers with the opportunity to analyze
      identical material, while having virtually no disadvantage in their respective tasks. The
      investigators have recently shown the ability of our methodology to find new markers in the
      context of precious human colorectal cancer samples. Thus, the investigators are convinced
      that EXPEL can be successfully applied to pancreatic cancer. In addition, knowing the
      important proportion of stroma in PDAC (usually 2/3 of tumor mass), the secretome of
      pancreatic cancer is expected to be much richer in soluble "communication factors" exchanged
      between cancer cells and host tissue.

      In clinical practice, most of patients undergo endoscopic ultrasound with fine needle
      aspiration/biopsy of the pancreatic mass to confirm the diagnosis of PDAC. The needle is
      rinsed in a conservation liquid Cytolyt® (Methanol 30% et water 50%) and sent to the
      pathologists. Microbiopsy are fixed in paraffin then analyzed and liquid is cytofiltrated to
      keep potential tumor cells. The remnant Cytolyt® liquid is systematically trashed.

      The present study is based on the hypothesis that this liquid, previously in contact with
      tumoral tissue, could contain the tissue secretome and permit a comprehensive OMICS analysis
      of PDAC (all stages confounded) by using a "modified EXPEL" procedure. These are ideal
      conditions for EXPEL approach that will additionally to finding novel biomarkers also shed
      light on complex network of cancer cell - stroma interactions.

      For this purpose, the investigators aim to perform proteomic analysis on the conservation
      liquid (Cytolyt) in patients who underwent endoscopic ultrasound with fine needle
      aspiration/biopsy for suspicious pancreatic mass at the CHU de Montpellier between Jan 2018
      and Jan 2019.
observational model: Cohort
time perspective: Retrospective
measure: Predictive value of each protein contained in Cytolyt® for the positive diagnosis of pancreatic ductal adenocarcinoma
time frame: an average of 1 year
description: Correlation with positive diagnosis of pancreatic ductal adenocarcinoma and proteins quantity in Cytolyt® samples using ROC curves (sensibility/specificity: Area Under the Curve > 0.85) and binary logistic regression method with controlling for the effects of the co-variates (such as age, disease cTNM stage, and treatment details).
measure: Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis
time frame: 1 year
description: Disease-free survival (percentage of patients without recurrence) at 1 year
measure: Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis
time frame: 1 year
description: Overall survival at 1 year (percentage of patients alive)
measure: Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis
time frame: 1 year
description: Disease-free survival (DFS) (time from diagnosis to time of first radiological evidence of local, regional, or distant relapse, or death due to any cause)
measure: Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis
time frame: 1 year
description: Overall survival (OS) (time from diagnosis until death, regardless of cause)
measure: Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis
time frame: 1 year
description: Kaplan Meier analysis, logrank test and Cox's proportional hazards regression model to identify biomarkers that are prognostically significant (Hazard ratio (HR) and its 95% confidence interval (CI)).
Cytolyt Samples:

      Liquid conservation samples from patients who underwent endoscopic ultrasound with fine
      needle aspiration/biopsy for suspicious pancreatic mass at the CHU de Montpellier were
      conserved at +4°c.

      Cytolyt samples do not contain any cell or tissue from patient, this liquid is systematically
      trashed in current practice. No genetics analysis will be performed from these particular
      samples in the present study.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: REGIS SOUCHE
role: Study Director
affiliation: University Hospital, Montpellier
last name: REGIS SOUCHE, MD
phone: 467337072
phone ext: 33
email: fr-souche@chu-montpellier.fr
last name: Jean-Michel Fabre, MD, PhD
phone: 467337072
phone ext: 33
email: jm-fabre@chu-montpellier.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms