<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/NCT03787056</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL18_0369</org_study_id>
    <nct_id>NCT03787056</nct_id>
  </id_info>
  <brief_title>Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients</brief_title>
  <acronym>ONCOPRO</acronym>
  <official_title>Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Progastrin is a pro-hormone that, in physiological conditions, is maturated in gastrin in G&#xD;
      cells of the stomach. The role of the gastrin is to stimulate the secretion of gastric acids&#xD;
      during digestion. It is also important for the regulation of cell growth of the gastric&#xD;
      mucosal.&#xD;
&#xD;
      In a healthy person, progastrin is not detectable in the peripheral blood. However,&#xD;
      progastrin is abnormally released in the blood of patients with different cancers&#xD;
      (colorectal, gastric, ovarian, breast, cervix uterus, melanoma…) The gene GAST coding for&#xD;
      progastrin is a direct target gene of the WNT/ß-catenin oncogenic pathway. The activation of&#xD;
      this oncogenic pathway is an early event in cancer development.&#xD;
&#xD;
      Chronic activation of the WNT/ß-catenin oncogenic pathway occurs in almost all human solid&#xD;
      tumors and is a central mechanism in cancer biology that induces cellular proliferation,&#xD;
      blocking of differentiation leading to primary tumor growth and metastasis formation.&#xD;
&#xD;
      Progastrin measured in the peripheral blood of patients on treatments, could be a new&#xD;
      powerful marker for diagnosis and prognosis at different stages.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 4, 2018</start_date>
  <completion_date type="Anticipated">January 4, 2028</completion_date>
  <primary_completion_date type="Anticipated">January 4, 2028</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ROC curve AUC regarding diagnostic accuracy of progastrin levels at baseline in cancer patients compared to non-cancer controls</measure>
    <time_frame>At baseline</time_frame>
    <description>Progastrin concentration in plasma samples will be measured with an ELISA Kit (CancerREAD LAB) provided by ECS Progastrin.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Longitudinal kinetic of progastrin values during treatments, assessed by modeled kinetic parameters of interest</measure>
    <time_frame>6 years</time_frame>
    <description>A nonlinear mixed effect model will be used to model the progastrin measurements done during treatments and follow-up of patients.The effect of each event (chemotherapy, surgery…) on the progastrin value and in the inter-individual variability of production and/or elimination rates of progastrin will be analyzed. Progastrin will be measured by ELISA, and the values will be expressed in pM.&#xD;
Measures will be done depending on the treatment received. Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nycthemeral and weekly and post-operative progastrin variations</measure>
    <time_frame>every 3 hours within 24 hours for the Nycthemeral cohort, and every week for 2 or 3 weeks for the weekly cohort</time_frame>
    <description>24 patients will be selected, upon their agreement and serum high levels, to enter in nychtemer (12 patients) or weekly (12 patients) cohorts. For the Nychtemer cohort, progastrin will be assayed at d1 at 8:00 am; 11:00 am; 2:00 pm; 5:00 pm; 8:00 pm and at d2 at 8:00 For the weekly cohort, progastrin will be assayed Day 1; Day 8; Day 15 and +/- Day 22; ideally on the same hour times. Progastrin will be measured by ELISA, and the values will be expressed in pM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determinants of progastrin serum values: hepatic function</measure>
    <time_frame>6 years</time_frame>
    <description>A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (hepatic function, as measured by the concentration of AST, ALT and bilirubin).&#xD;
Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determinants of progastrin serum values: renal function</measure>
    <time_frame>6 years</time_frame>
    <description>A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (renal function, as measured by creatinin concentration and creatinin clearance).&#xD;
Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determinants of progastrin serum values: age</measure>
    <time_frame>at the inclusion</time_frame>
    <description>A nonlinear mixed effect model will be used to correlate the individual characteristics of the patient (age and gender) with progastrin concentration at the inclusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determinants of progastrin serum values: gender</measure>
    <time_frame>at the inclusion</time_frame>
    <description>A nonlinear mixed effect model will be used to correlate genders with progastrin concentrations at the inclusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>6 years</time_frame>
    <description>The relationships between the progastrin kinetics during and after treatment and overall survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.&#xD;
Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>recurrence free survival</measure>
    <time_frame>6 years</time_frame>
    <description>The relationships between the progastrin kinetics during and after treatment and recurrence free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.&#xD;
Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>progression free survival</measure>
    <time_frame>6 years</time_frame>
    <description>The relationships between the progastrin kinetics during and after treatment and progression free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.&#xD;
Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The tumor size at cancer diagnosis</measure>
    <time_frame>At baseline</time_frame>
    <description>The size of the tumor will be correlated to progastrin concentration at the time of cancer diagnosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete surgery</measure>
    <time_frame>6 years</time_frame>
    <description>The ability of progastrin kinetics during the neoadjuvant period to predict the outcome of the surgery (complete or not) will be analyzed by a ROC curve. If applicable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to recurrence (for patients enrolled in curative intent cohorts).</measure>
    <time_frame>6 years</time_frame>
    <description>The ability of the progastrin kinetics to predict recurrence free survival (curative cohorts), will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to progression (for patients enrolled in non-curative intent cohorts)</measure>
    <time_frame>6 years</time_frame>
    <description>The ability of the progastrin kinetics to predict progression-free survival (non-curative cohorts) will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to death (whenever it occurred)</measure>
    <time_frame>6 years</time_frame>
    <description>The ability of the progastrin kinetics to predict time to death will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the initial values and of the kinetics of other serum tumor markers (CA15-3, CA 19-9, CA125, CEA, PSA, AFP) with those of progastrin</measure>
    <time_frame>at the baseline</time_frame>
    <description>The ROC AUC will be compared between classical markers and the prograstrin. Logistic regression will be used to combine the classical marker(s) and the progastrin in order to estimate the diagnostic value of the marker combination.&#xD;
progastrin, CA15-3, CA19-9, CA125, CEA, PSA and AFP concentration will be measured on blood sample taken at the inclusion.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">410</enrollment>
  <condition>Cancer</condition>
  <condition>Breast Cancer</condition>
  <condition>Gastric Cancer</condition>
  <condition>Renal Cancer</condition>
  <condition>Prostate Cancer</condition>
  <condition>Melanoma</condition>
  <condition>Lung Cancer</condition>
  <condition>Hepatocellular Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Head and Neck Cancer</condition>
  <condition>Pancreatic Cancer</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Glioblastoma</condition>
  <condition>Endometrial Cancer</condition>
  <condition>Bladder Cancer</condition>
  <condition>Esophageal Cancer</condition>
  <condition>B-cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Cancer patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>420 patients affected by different types of cancer and treated in a curative or a palliative intent. In total 17 cohorts will be open, including: breast cancer, head and neck carcinomas, renal cell carcinoma, prostate carcinoma, lung carcinoma, hepatocellular carcinoma, colorectal carcinoma, thyroid cancer, pancreatic adenocarcinoma, ovarian adenocarcinoma, glioblastoma, endometrial adenocarcinoma, bladder carcinoma, oesophago-gastric carcinoma, B-cell lymphoma, gastric carcinomas. Patients enrolled in curative intent treatment cohorts will never have been previously treated for their cancer. Patients enrolled in non-curative intent treatment cohorts will have never been treated for their metastatic cancers previously, or have developed advanced/metastatic diseases as relapses of localized cancers previously treated with curative intent therapeutic strategies. Other cohort will be open (stability cohorts) : nychtemer cohort and post-operative kinetic cohort.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood draws</intervention_name>
    <description>Blood draws are realized at each steps of patient disease management. The volume of each blood drawn is 25 mL for progastrin measurements and 5 mL for the dosage of the other tumor markers. The frequency depend to the cancer and treatment administered :&#xD;
Baseline at diagnosis : Local radical treatment : within 24h before surgery, within 24h after surgery and at the post-surgery follow up visit&#xD;
Chemotherapy treatment : every 3 or 4 weeks&#xD;
Radiotherapy : start day and at the end of radiation (&quot;end of treatment&quot; visit)&#xD;
Palliative systemic treatment (only palliative cohorts) : every 3 to 12 weeks. Follow until the third progression or change of treatment line, or alternatively up to 5 years after inclusion&#xD;
In case of PD or TOX&#xD;
Follow up: at each visit scheduled (every 3 months) for the first 2 years, then every 6 months for 3 years&#xD;
Relapse : withdrawn from the study and last progastrin measurement. Patient could be enrolled in the non-curative intent cohort</description>
    <arm_group_label>Cancer patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Histologically and/or cytologically documented (documentation obtained before or after&#xD;
             diagnostic surgical procedure when clinical suspicion is strong), cancers for the&#xD;
             following cohorts:&#xD;
&#xD;
             o Breast carcinomas&#xD;
&#xD;
             o Gastric carcinomas&#xD;
&#xD;
             o Renal carcinomas&#xD;
&#xD;
             o Prostate carcinomas&#xD;
&#xD;
             o Lung carcinomas: NSCLC and SCLC&#xD;
&#xD;
             o Hepatocellular carcinomas&#xD;
&#xD;
             o Colorectal carcinomas&#xD;
&#xD;
               -  Head and neck carcinomas&#xD;
&#xD;
               -  Thyroid cancer&#xD;
&#xD;
               -  Pancreatic carcinomas&#xD;
&#xD;
               -  Ovarian adenocarcinomas&#xD;
&#xD;
               -  Glioblastoma&#xD;
&#xD;
               -  Endometrial adenocarcinomas&#xD;
&#xD;
               -  Bladder carcinoma&#xD;
&#xD;
               -  Superficial Oesophago-gastric carcinomas&#xD;
&#xD;
               -  Diffuse Large B-cell Lymphomas&#xD;
&#xD;
          -  Patient older than 18 years.&#xD;
&#xD;
          -  Patients who gave its written informed consent to participate to the study&#xD;
&#xD;
          -  Patients affiliated to a social insurance regime&#xD;
&#xD;
        Specific inclusion criteria for curative treatment strategy cancer patients:&#xD;
&#xD;
          -  Indication of a treatment strategy with curative intent (surgery; radiotherapy;&#xD;
             chemotherapy; hormonotherapy; targeted agents…)&#xD;
&#xD;
          -  Patient naïve of anticancer treatments for the considered cancer&#xD;
&#xD;
          -  A prior anti-cancer treatment is allowed if this treatment was performed with curative&#xD;
             intent, and if it did not include systemic chemotherapy, and if a complete remission ≥&#xD;
             6 months was observed in between the end of treatment and relapse. Previous local&#xD;
             treatments for superficial lesions are allowed without any time restriction (for&#xD;
             example among others, intravesical treatment for superficial bladder cancer lesions).&#xD;
&#xD;
        Specific inclusion criteria for non-curative treatment strategy cancer patients:&#xD;
&#xD;
          -  Indication of a treatment strategy with no curative intent (radiotherapy;&#xD;
             chemotherapy; hormonotherapy; immunotherapy; targeted agents, non-curative surgery, …)&#xD;
&#xD;
          -  Patient naïve of anticancer treatments in non-curative setting (except for metastatic&#xD;
             hormone-sensitive prostate cancer, see specific inclusion criteria).&#xD;
&#xD;
        The following tumor type specific inclusion criteria must be met in addition to the&#xD;
        inclusion criteria listed above:&#xD;
&#xD;
        Breast carcinomas&#xD;
&#xD;
        • All cohorts:&#xD;
&#xD;
          -  Invasive breast ductal carcinoma, or&#xD;
&#xD;
          -  Invasive breast lobular carcinoma&#xD;
&#xD;
               -  Curative intent treatment patient cohort:&#xD;
&#xD;
          -  Planned to be treated with surgery, with/without neo-adjuvant and/or adjuvant&#xD;
             chemotherapy and/or anti-hormone treatment&#xD;
&#xD;
        Gastric carcinomas&#xD;
&#xD;
          -  All cohorts:&#xD;
&#xD;
             o Intestinal-type adenocarcinoma, or&#xD;
&#xD;
             o Diffuse cell type adenocarcinoma&#xD;
&#xD;
          -  Curative intent treatment patient cohort:&#xD;
&#xD;
               -  Planned to be treated with surgery with/without neo-adjuvant treatment,&#xD;
                  with/without adjuvant treatment&#xD;
&#xD;
        Renal carcinomas • All cohorts:&#xD;
&#xD;
          -  Any histology of renal cancer is accepted (non-clear cell renal cancer could be&#xD;
             included)&#xD;
&#xD;
          -  A pathology proof of renal cell carcinoma is not necessarily provided if patients&#xD;
             present typical radiologic characteristics of renal cancer on imaging&#xD;
&#xD;
             • Curative intent treatment patients cohort:&#xD;
&#xD;
          -  Planned to be treated with partial or total nephrectomy&#xD;
&#xD;
        Prostate carcinomas&#xD;
&#xD;
          -  Curative intent treatment patients cohort:&#xD;
&#xD;
             o Localized prostate cancer with high risk features : StageT2b , T2c or T3 and/or&#xD;
             Gleason &gt;= 4+3 and/or PSA &gt;= 20 and/or N+&#xD;
&#xD;
             o Planned to be treated with radical prostatectomy or radiotherapy (potentially&#xD;
             associated with androgen deprivation therapy). Brachytherapy and/or focused&#xD;
             ultrasounds are not allowed.&#xD;
&#xD;
          -  Non-curative intent treatment patients cohort:&#xD;
&#xD;
               -  Patients with metastatic castration resistant prostate cancer (mCRPC) defined by&#xD;
                  validated criteria of EAU, planned to be treated with doceteaxel or cabazitaxel&#xD;
                  or second generation hormone (i.e. abiraterone or enzalutamide). Patients have to&#xD;
                  be naïve of treatment for the castration resistant mCRPC. Patients that&#xD;
                  previously received docetaxel or a 1st or 2nd generation hormonotherapy for their&#xD;
                  hormone-sensitive prostate cancer in metastatic setting can be included.&#xD;
&#xD;
        Lung carcinomas treated by immunotherapy :&#xD;
&#xD;
        • Non-curative intent patients cohort:&#xD;
&#xD;
        o NSCLC stage IV according to 8th TNM classification planned to be treated with&#xD;
        immunotherapy, with/ without chemotherapy&#xD;
&#xD;
        Lung carcinomas excluding those treated with immunotherapy:&#xD;
&#xD;
          -  Curative intent treatment patients cohort:&#xD;
&#xD;
             o NSCLC histology only&#xD;
&#xD;
             o Stage I-II according to 8th TNM classification&#xD;
&#xD;
             o Stage IIIA-B according to 8th TNM classification&#xD;
&#xD;
             o Planned to be treated with radical treatment (surgery or radiotherapy with/without&#xD;
             concurrent chemotherapy), potentially associated with neo-adjuvant or adjuvant&#xD;
             treatment&#xD;
&#xD;
          -  Non-curative intent patients cohort:&#xD;
&#xD;
               -  NSCLC or SCLC stage IV according to 8th TNM classification planned to be treated&#xD;
                  with a first line of chemotherapy, with/without associated treatments except&#xD;
                  immunotherapy (radiotherapy, targeted therapies…). Immunotherapy can be&#xD;
                  administrated for the subsequent lines of treatment.&#xD;
&#xD;
        Hepatocellular carcinomas A pathology proof of HCC is not necessarily provided if patients&#xD;
        present typical radiologic characteristics of hepatocellular carcinoma on imaging&#xD;
&#xD;
          -  Absence or chronic hepatic encephalopathy, absence of refractory ascites&#xD;
&#xD;
               -  Curative intent treatment patients cohort:&#xD;
&#xD;
          -  Indication of a treatment strategy with curative intent, except liver transplantation:&#xD;
             surgical resection, monopolar radiofrequency ablation for HCC (1 to 3 nodules ≤3 cm)&#xD;
             or multibipolar radiofrequency if nodule ≤4 cm).&#xD;
&#xD;
             • Non-curative intent patients cohort:&#xD;
&#xD;
          -  Indication of a treatment strategy with no curative intent: transarterial&#xD;
             intra-hepatic chemoembolization, targeted therapies (tyrosine kinase inhibitors or&#xD;
             monoclonal antibodies) or immune therapy.&#xD;
&#xD;
        Colorectal carcinomas&#xD;
&#xD;
        • Curative intent treatment patients cohort:&#xD;
&#xD;
        o Lieberkühn adenocarcinoma associated with metastases planned to be treated with&#xD;
        peri-operative chemotherapy +/- targeted agent and interval surgery&#xD;
&#xD;
        Head and neck carcinomas&#xD;
&#xD;
          -  All cohorts&#xD;
&#xD;
             o Head and neck squamous cell carcinoma from oral cavity, oropharynx, hypopharynx,&#xD;
             larynx&#xD;
&#xD;
          -  Curative intent treatment patients cohort:&#xD;
&#xD;
             o Planned to be treated with a radical treatment (surgery and/or radiotherapy&#xD;
             potentially associated with concurrent chemotherapy) with/without&#xD;
             neo-adjuvant/adjuvant chemotherapy.&#xD;
&#xD;
          -  Non-curative intent treatment patients cohort:&#xD;
&#xD;
             o De novo metastatic or metastatic/loco-regional relapse planned to be treated with&#xD;
             chemotherapy and/or immunotherapy&#xD;
&#xD;
        Thyroid cancer • Curative intent patient cohort o Thyroid carcinoma differentiated, poorly&#xD;
        differentiated, papillary, vesicular, Hurthle Cell o For which a iodine treatment is&#xD;
        indicated (Iodine treatment will be discussed after surgery. In the case the histological&#xD;
        result does not confirm a high risk thyroid cancer, patient will be withdrawn from the&#xD;
        study. In the same way, if a iodine treatment is not recommended after surgery, patient&#xD;
        will be withdrawn from the study. In both cases, patient will be replaced).&#xD;
&#xD;
        Pancreatic carcinomas&#xD;
&#xD;
        • Curative intent patients cohort:&#xD;
&#xD;
        o Pancreas exocrine adenocarcinoma planned to be treated with initial surgery with/without&#xD;
        neo-adjuvant chemotherapy and with/without adjuvant chemotherapy or radiotherapy&#xD;
&#xD;
        Ovarian adenocarcinomas • Non/uncertain curative intent patients cohort:&#xD;
&#xD;
        o 1st platinum-sensitive relapse&#xD;
&#xD;
          -  High or low grade epithelial adenocarcinomas or carcinosarcoma&#xD;
&#xD;
          -  Planned to be treated with chemotherapy and/or PARP inhibitors based treatment, +/-&#xD;
             interval debulking surgery&#xD;
&#xD;
        Glioblastoma • Curative intent patients cohort:&#xD;
&#xD;
        o Planned to be treated with surgical resection, followed by adjuvant temozolomide and&#xD;
        radiotherapy&#xD;
&#xD;
        Endometrial adenocarcinomas&#xD;
&#xD;
          -  Non-curative intent patients cohort:&#xD;
&#xD;
             o Type 1 (endometrioid or mucinous) or type 2 endometrial (serous, clear cell,&#xD;
             undifferentiated carcinoma and carcinosarcoma) cancers&#xD;
&#xD;
             o Planned to be treated with non-curative systemic treatment for metastatic or&#xD;
             advanced disease&#xD;
&#xD;
        Bladder carcinoma&#xD;
&#xD;
          -  Transitional cell carcinoma • Curative intent treatment patients:&#xD;
&#xD;
          -  Patients with localized muscle invasive bladder cancer (&gt;=PT2)&#xD;
&#xD;
          -  Planned to be treated with neo-adjuvant cisplatin based chemotherapy, or immunotherapy&#xD;
             or a combination of chemotherapy and immunotherapy&#xD;
&#xD;
        Superficial Oesophago-gastric cancer • Curative intent patients cohort:&#xD;
&#xD;
        o Superficial oesophago-gastric carcinomas (adenocarcinomas or epidermoid carcinomas) of&#xD;
        Stage T1 planned to be treated by endoscopic surgery&#xD;
&#xD;
        Diffuse Large B-Cell Lymphoma (DLBCL)&#xD;
&#xD;
        • Curative intent patients cohort:&#xD;
&#xD;
        o Patients planned to be treated with R-CHOP (Rituximab-Cyclophosphamide,&#xD;
        Hydroxyadriamycine, Oncovin, Prednisone)&#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>Benoit YOU, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospices Civils de Lyon</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Benoit YOU, MD</last_name>
    <phone>04 78 86 43 53</phone>
    <phone_ext>+33</phone_ext>
    <email>benoit.you@hu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sara CALATTINI</last_name>
    <phone>04 78 86 37 79</phone>
    <phone_ext>+33</phone_ext>
    <email>sara.calattini@chu-lyon.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Service de NEURO-ONCOLOGIE du Groupement Hospitalier EST</name>
      <address>
        <city>Bron</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francois DUCRAY, MD</last_name>
      <email>francois.ducray@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Francois DUCRAY, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'hôpital de la Croix-Rousse</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marielle GUILLET, MD</last_name>
      <email>marielle.guillet@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Marielle GUILLET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Philippe MERLE, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE de l'Hôpital E. Herriot</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas WALTER, MD</last_name>
      <email>thomas.walter@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Thomas WALTER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mathieu PIOCHE, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'Oto-Rhino-Laryngologie de l'Hôpital de la Croix-Rousse</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amandine BRUYAS, MD</last_name>
      <email>amandine.bruyas@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Amandine BRUYAS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Philippe CERUSE, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'Urologie de l'Hôpital E. Herriot</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lionel BADET, MD</last_name>
      <email>lionel.badet@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Lionel BADET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Gynécologie de l'hôpital de la Croix-Rousse</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marion CORTET, MD</last_name>
      <email>marion.cortet@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Marion CORTET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Gynécologie du Groupement Hospitalier Est</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christophe SAJOUS, MD</last_name>
      <email>christophe.sajous@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Christophe SAJOUS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Pneumologie de l'hôpital de la Croix-Rousse</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gilles DEVOUASSOUX, MD</last_name>
      <email>gilles.devouassoux@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Gilles DEVOUASSOUX, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lize KIAKOUAMA, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Pneumologie du Groupement Hospitalier Est</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael DURUISSEAUX, MD</last_name>
      <email>michael.duruisseaux@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Michael DURUISSEAUX, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'Hématologie de l'Hôpital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lionel KARLIN, MD</last_name>
      <email>lionel.karlin@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Lionel KARLIN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'ONCOLOGIE DIGESTIVE et HEPATOLOGIE du Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marion CHAUVENET, MD</last_name>
      <email>marion.chauvenet@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Marion CHAUVENET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'Oncologie médicale du Centre hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benoit YOU, MD</last_name>
      <email>benoit.you@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Benoit YOU, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gilles FREYER, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Véronique TRILLET LENOIR, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Denis MAILLET, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sophie TARTAS, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nathalie BONNIN, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Julien PERON, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Olivia LE SAUX, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service d'Urologie de l'hôpital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Philippe PAPAREL, MD</last_name>
      <email>philippe.paparel@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Philippe PAPAREL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Chirurgie de l'hôpital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier GLEHEN, MD</last_name>
      <email>olivier.glehen@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Olivier GLEHEN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Naoual BAKRIN, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Dermatologie de l'hôpital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephane DALLE, MD</last_name>
      <email>stephane.dalle@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Stephane DALLE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mona AMINI, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Gynécologie de l'hôpital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre Adrien BOLZE, MD</last_name>
      <email>pierre-adrien.bolze@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Pierre Adrien BOLZE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Pneumologie de l'Hôpital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sebastien COURAUD, MD</last_name>
      <email>sebastien.couraud@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Sebastien COURAUD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>October 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>July 12, 2021</last_update_submitted>
  <last_update_submitted_qc>July 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>dd</keyword>
  <keyword>TUMOR MARKER</keyword>
  <keyword>PROGASTRIN</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Kidney Neoplasms</mesh_term>
    <mesh_term>Liver Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</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/NCT03787056
org study id: 69HCL18_0369
nct id: NCT03787056
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Progastrin is a pro-hormone that, in physiological conditions, is maturated in gastrin in G
      cells of the stomach. The role of the gastrin is to stimulate the secretion of gastric acids
      during digestion. It is also important for the regulation of cell growth of the gastric
      mucosal.

      In a healthy person, progastrin is not detectable in the peripheral blood. However,
      progastrin is abnormally released in the blood of patients with different cancers
      (colorectal, gastric, ovarian, breast, cervix uterus, melanoma…) The gene GAST coding for
      progastrin is a direct target gene of the WNT/ß-catenin oncogenic pathway. The activation of
      this oncogenic pathway is an early event in cancer development.

      Chronic activation of the WNT/ß-catenin oncogenic pathway occurs in almost all human solid
      tumors and is a central mechanism in cancer biology that induces cellular proliferation,
      blocking of differentiation leading to primary tumor growth and metastasis formation.

      Progastrin measured in the peripheral blood of patients on treatments, could be a new
      powerful marker for diagnosis and prognosis at different stages.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: ROC curve AUC regarding diagnostic accuracy of progastrin levels at baseline in cancer patients compared to non-cancer controls
time frame: At baseline
description: Progastrin concentration in plasma samples will be measured with an ELISA Kit (CancerREAD LAB) provided by ECS Progastrin.
measure: Longitudinal kinetic of progastrin values during treatments, assessed by modeled kinetic parameters of interest
time frame: 6 years
description: A nonlinear mixed effect model will be used to model the progastrin measurements done during treatments and follow-up of patients.The effect of each event (chemotherapy, surgery…) on the progastrin value and in the inter-individual variability of production and/or elimination rates of progastrin will be analyzed. Progastrin will be measured by ELISA, and the values will be expressed in pM.
Measures will be done depending on the treatment received. Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients.
measure: Nycthemeral and weekly and post-operative progastrin variations
time frame: every 3 hours within 24 hours for the Nycthemeral cohort, and every week for 2 or 3 weeks for the weekly cohort
description: 24 patients will be selected, upon their agreement and serum high levels, to enter in nychtemer (12 patients) or weekly (12 patients) cohorts. For the Nychtemer cohort, progastrin will be assayed at d1 at 8:00 am; 11:00 am; 2:00 pm; 5:00 pm; 8:00 pm and at d2 at 8:00 For the weekly cohort, progastrin will be assayed Day 1; Day 8; Day 15 and +/- Day 22; ideally on the same hour times. Progastrin will be measured by ELISA, and the values will be expressed in pM.
measure: Determinants of progastrin serum values: hepatic function
time frame: 6 years
description: A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (hepatic function, as measured by the concentration of AST, ALT and bilirubin).
Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients
measure: Determinants of progastrin serum values: renal function
time frame: 6 years
description: A nonlinear mixed effect model will be used to correlate individual values of progastrin (expressed in pM) with individual characteristic on the patient (renal function, as measured by creatinin concentration and creatinin clearance).
Measures will be done Chemotherapy, every 3 or 4 weeks. Oral treatments: every 3 to 12 weeks. Surgery or radiotherapy: before and after the treatment. Follow up: concomitantly to the visits scheduled for the regular follow up of the patients
measure: Determinants of progastrin serum values: age
time frame: at the inclusion
description: A nonlinear mixed effect model will be used to correlate the individual characteristics of the patient (age and gender) with progastrin concentration at the inclusion.
measure: Determinants of progastrin serum values: gender
time frame: at the inclusion
description: A nonlinear mixed effect model will be used to correlate genders with progastrin concentrations at the inclusion.
measure: Overall survival
time frame: 6 years
description: The relationships between the progastrin kinetics during and after treatment and overall survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.
Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.
measure: recurrence free survival
time frame: 6 years
description: The relationships between the progastrin kinetics during and after treatment and recurrence free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.
Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.
measure: progression free survival
time frame: 6 years
description: The relationships between the progastrin kinetics during and after treatment and progression free survival will be analyzed. Analyses will be performed separately on patients with curative intent treatment and on patients with palliative intent treatment.
Measures wil be done At the end of the study (6 years for patients enrolled in curative intent and 5 years for patients enrolled in non-curative intent) or alternatively at the occurrence of progression or relapse.
measure: The tumor size at cancer diagnosis
time frame: At baseline
description: The size of the tumor will be correlated to progastrin concentration at the time of cancer diagnosis
measure: Complete surgery
time frame: 6 years
description: The ability of progastrin kinetics during the neoadjuvant period to predict the outcome of the surgery (complete or not) will be analyzed by a ROC curve. If applicable.
measure: time to recurrence (for patients enrolled in curative intent cohorts).
time frame: 6 years
description: The ability of the progastrin kinetics to predict recurrence free survival (curative cohorts), will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up.
measure: time to progression (for patients enrolled in non-curative intent cohorts)
time frame: 6 years
description: The ability of the progastrin kinetics to predict progression-free survival (non-curative cohorts) will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up
measure: time to death (whenever it occurred)
time frame: 6 years
description: The ability of the progastrin kinetics to predict time to death will be based on parameters estimated with a PK/PD model able to characterize the early kinetics of progastrin during and after the end of treatment and during follow up
measure: Comparison of the initial values and of the kinetics of other serum tumor markers (CA15-3, CA 19-9, CA125, CEA, PSA, AFP) with those of progastrin
time frame: at the baseline
description: The ROC AUC will be compared between classical markers and the prograstrin. Logistic regression will be used to combine the classical marker(s) and the progastrin in order to estimate the diagnostic value of the marker combination.
progastrin, CA15-3, CA19-9, CA125, CEA, PSA and AFP concentration will be measured on blood sample taken at the inclusion.
arm group label: Cancer patients
arm group type: Other
description: 420 patients affected by different types of cancer and treated in a curative or a palliative intent. In total 17 cohorts will be open, including: breast cancer, head and neck carcinomas, renal cell carcinoma, prostate carcinoma, lung carcinoma, hepatocellular carcinoma, colorectal carcinoma, thyroid cancer, pancreatic adenocarcinoma, ovarian adenocarcinoma, glioblastoma, endometrial adenocarcinoma, bladder carcinoma, oesophago-gastric carcinoma, B-cell lymphoma, gastric carcinomas. Patients enrolled in curative intent treatment cohorts will never have been previously treated for their cancer. Patients enrolled in non-curative intent treatment cohorts will have never been treated for their metastatic cancers previously, or have developed advanced/metastatic diseases as relapses of localized cancers previously treated with curative intent therapeutic strategies. Other cohort will be open (stability cohorts) : nychtemer cohort and post-operative kinetic cohort.
intervention type: Other
intervention name: Blood draws
description: Blood draws are realized at each steps of patient disease management. The volume of each blood drawn is 25 mL for progastrin measurements and 5 mL for the dosage of the other tumor markers. The frequency depend to the cancer and treatment administered :
Baseline at diagnosis : Local radical treatment : within 24h before surgery, within 24h after surgery and at the post-surgery follow up visit
Chemotherapy treatment : every 3 or 4 weeks
Radiotherapy : start day and at the end of radiation ("end of treatment" visit)
Palliative systemic treatment (only palliative cohorts) : every 3 to 12 weeks. Follow until the third progression or change of treatment line, or alternatively up to 5 years after inclusion
In case of PD or TOX
Follow up: at each visit scheduled (every 3 months) for the first 2 years, then every 6 months for 3 years
Relapse : withdrawn from the study and last progastrin measurement. Patient could be enrolled in the non-curative intent cohort
arm group label: Cancer patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Benoit YOU, MD
role: Principal Investigator
affiliation: Hospices Civils de Lyon
last name: Benoit YOU, MD
phone: 04 78 86 43 53
phone ext: +33
email: benoit.you@hu-lyon.fr
last name: Sara CALATTINI
phone: 04 78 86 37 79
phone ext: +33
email: sara.calattini@chu-lyon.fr
facility: 
status: Recruiting
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country: France
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Endometrial Neoplasms
mesh term: Kidney Neoplasms
mesh term: Liver Neoplasms
mesh term: Carcinoma, Hepatocellular