<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/NCT03806309</url>
  </required_header>
  <id_info>
    <org_study_id>TEDOPAM D17-01 PRODIGE 63</org_study_id>
    <nct_id>NCT03806309</nct_id>
  </id_info>
  <brief_title>Maintenance With OSE2101 Plus FOLFIRI, or FOLFIRI After FOLFIRINOX-based Induction Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma</brief_title>
  <acronym>TEDOPAM</acronym>
  <official_title>A Randomized Non-comparative Phase II Study of Maintenance Therapy With OSE2101 Plus FOLFIRI, or FOLFIRI After Induction Therapy With FOLFIRINOX in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (TEDOPaM-D17-01 PRODIGE 63 Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GERCOR - Multidisciplinary Oncology Cooperative Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>OSE Immunotherapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GERCOR - Multidisciplinary Oncology Cooperative Group</source>
  <oversight_info>
    <has_dmc>Yes</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>
      TEDOPAM is a randomized (1.1.1) non-comparative phase II study. This study will assess the&#xD;
      efficacy and safety of OSE2101 alone or in combination with nivolumab followed by FOLFIRI&#xD;
      reintroduction, versus FOLFIRI as maintenance therapy in patients with advanced PDAC after&#xD;
      induction therapy with FOLFIRINOX.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current standard of care for patients with advanced pancreatic ductal adenocarcinoma (PDAC)&#xD;
      is chemotherapy, preferential regimen being FOLFIRINOX (5FU, leucovorin, irinotecan, and&#xD;
      oxaliplatin) in fit patients (PS 0-1, bilirubin &lt; 1.5 ULN). The question of how and when the&#xD;
      FOLFIRINOX regimen and doses can be deescalated after a period of disease control (i.e.&#xD;
      maintenance therapy) remains unanswered. In routine practice, oxaliplatin is usually stopped&#xD;
      after 6-8 cycles due to limiting neuropathy, and the fluoropyrimidine is continued, either&#xD;
      alone or, more frequently, in combination with irinotecan (FOLFIRI regimen), until disease&#xD;
      progression.&#xD;
&#xD;
      Immune therapies have opened new opportunities in cancer therapy. However, results of&#xD;
      immunotherapy in PDAC have been disappointing so far, with failure of checkpoint inhibitor&#xD;
      monotherapies (anti-CTLA4 and anti-PD-L1 monoclonal antibodies [mAb]) in progressive advanced&#xD;
      PDAC, while monovalent vaccines were demonstrated to be safe but with limited activity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 31, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>At 12 months</time_frame>
    <description>The OS is defined according to the DATECAN (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) consensus as the time from randomization to death for any reason. In the absence of confirmation of death, survival time will be censored at the date of the last clinical assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) by centralized review of CT-scan imaging.</measure>
    <time_frame>assessed up to 60 months</time_frame>
    <description>The PFS is defined according to the DATECAN consensus as the time from randomization to first progression or death for any reason, whichever occurs first. In the absence of event (confirmation of progression or death), PFS status will be censored at the date of the last radiological assessment.&#xD;
PFS according to RECIST (Response Evaluation Criteria In Solid Tumors) v1.1 in the FOLFIRI arm (Arm A) and iRECIST (immune Response Evaluation Criteria In Solid Tumors) in the immune therapy arms (Arm B and C) by centralized review of CT-scan imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of patients with success of the strategy (SSR)</measure>
    <time_frame>At 6 months</time_frame>
    <description>The SSR is derived from the duration of disease control (DDC), which is defined as the PFS, or, if FOLFIRI is reintroduced and achieves partial response (PR) or stable disease (SD), as the addition of the initial PFS (PFS1) and the PFS of the reintroduction PFS (PFS2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCICTCAE] v5.0</measure>
    <time_frame>from signature of informed consent to 28 days after the last administration of the investigational product in Arm A and B and 100 days after the last administration of the investigational product in Arm C.</time_frame>
    <description>All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>assessed up to 60 months</time_frame>
    <description>Response according to RECIST v1.1 in the FOLFIRI arm (Arm A) and iRECIST in the immune therapy arms (Arms B and C) (centralized review of CT-scan imaging); a comparative analysis of tumor response according to these two evaluation rules will be performed in Arm B and C</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related Quality of life (HRQoL) evaluation assessed by EORTC QLQ (quality of life questionnaire) -C30 questionnaire</measure>
    <time_frame>Baseline, Month 2, Month 4, Month 6, Month 8, Month 10, Month 12, Month 14, Month 16, Month 18, Month 20, Month 22, Month 24 (until the date of first documented progression or date of death, assessed up 60 months)</time_frame>
    <description>Rate of patients with an improvement of their quality of life score according to EORTC QLQ-C30. A quality of life score is obtained according to the answers to the 30 questions. The Minimal Clinically Important Difference (MCID) will be fixed to 10 points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimate the Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment (Q-Twist) for each participant</measure>
    <time_frame>assessed up to 60 months</time_frame>
    <description>Q-TWiST analysis considers three health states, TOX (toxicity), TWiST, and REL (The duration of the relapse), and the duration of each state is calculated for every patient.&#xD;
The TOX state comprises the total number of days after randomisation and before strategy failure spent with toxicity, regardless of when the toxicity started or whether there were gaps between toxicities. All grade 3 or 4 toxicities attributable to the study drugs are included in the analysis, apart from those starting after strategy failure.&#xD;
The TWiST state is defined as DDC time minus time with toxicities.&#xD;
The duration of the relapse or REL state is defined as OS time minus DDC time, or the period of time from progression to death. Patients alive at the end of the study are censored for the OS endpoint.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">106</enrollment>
  <condition>Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Locally Advanced Cancer</condition>
  <condition>Metastatic Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A : maintenance with FOLFIRI</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>FOLFIRI (IV; folinic acid 400 mg/m^2, irinotecan 180 mg/m^2, 5-FU bolus 400 mg/m^2 and continuous infusion 2,400 mg/m^2/46h (dose adjustment will be accepted).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B : maintenance with OSE2101 plus FOLFIRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OSE2101 - subcutaneous injection on day 1 and day 15, every 4 weeks for 6 doses then every 8 weeks until month 12 then every 12 weeks up to 24 months.&#xD;
FOLFIRI - schedules as in Arm A until disease progression on unacceptable toxicity</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRI</intervention_name>
    <description>Intravenous (IV); folinic acid 400 mg/m^2, irinotecan 180 mg/m^2, 5-FU bolus 400 mg/m^2 and continuous infusion 2,400 mg/m^2</description>
    <arm_group_label>Arm A : maintenance with FOLFIRI</arm_group_label>
    <arm_group_label>Arm B : maintenance with OSE2101 plus FOLFIRI</arm_group_label>
    <other_name>Leucovorin (Folinic Acid), Fluorouracil, Irinotecan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OSE2101</intervention_name>
    <description>subcutaneous injection on days 1 and 15, every 4 weeks for 6 doses then every 8 weeks until month 12 and then every 12 weeks for a maximum treatment duration of 24 months</description>
    <arm_group_label>Arm B : maintenance with OSE2101 plus FOLFIRI</arm_group_label>
    <other_name>Tedopi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed and dated informed consent document, willing and able to comply with protocol&#xD;
             requirements,&#xD;
&#xD;
          2. Histologically or cytologically proven pancreatic ductal adenocarcinoma,&#xD;
&#xD;
          3. Age ≥ 18 years,&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1,&#xD;
&#xD;
          5. Human Leukocyte Antigen (HLA-A2) genotype,&#xD;
&#xD;
          6. Recurrent or advanced disease not amenable to surgery with curative intent (previous&#xD;
             resection of primary tumor allowed),&#xD;
&#xD;
          7. Measurable or evaluable (radiologically detectable disease which does not fulfill&#xD;
             RECIST criteria for measurable disease) lesions according to RECIST v1.1 criteria&#xD;
             (CT-scan &lt; 4 weeks),&#xD;
&#xD;
          8. Stable disease or tumor response according to RECIST v1.1 after a 4-month (8 cycles)&#xD;
             course of first-line FOLFIRINOX or modified FOLFIRINOX induction chemotherapy,&#xD;
&#xD;
          9. Have archival tissue sample that has been identified and confirmed as available for&#xD;
             study, or newly obtained core or excisional biopsy of a tumor lesion,&#xD;
&#xD;
         10. Adequate organ function, as defined by the following:&#xD;
&#xD;
               -  Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) &lt;&#xD;
                  3 x upper limit of normal (ULN),&#xD;
&#xD;
               -  Total serum bilirubin &lt; 1.5 ULN,&#xD;
&#xD;
               -  Prothrombin ratio &gt; 70%,&#xD;
&#xD;
               -  Serum albumin ≥ 2.8 g/dL,&#xD;
&#xD;
               -  Hemoglobin ≥ 10,0 g/dl,&#xD;
&#xD;
               -  White blood cell count (WBC) ≥ 3,000/μL,&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500/μL,&#xD;
&#xD;
               -  Platelets ≥ 100,000/μL,&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 ULN or creatinine clearance &gt; 50 mL/min (Modification of&#xD;
                  diet in renal disease [MDRD]),&#xD;
&#xD;
         11. Life expectancy ≥ 3 months,&#xD;
&#xD;
         12. Women participants of childbearing potential must have a negative serum pregnancy test&#xD;
             within the 3 days prior to the first treatment administration. Both women participants&#xD;
             of childbearing potential and men participants who are sexually active with women of&#xD;
             childbearing potential must agree to use a reliable method of birth control (i.e.&#xD;
             pregnancy rate &lt; 1% per year) until 6 months after the last dose of FOLFIRI, and 90&#xD;
             days after the last dose of OSE2101,&#xD;
&#xD;
         13. Registration in a national health care system (PUMA included).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Obstructive jaundice (bilirubin &gt; 1.5 ULN) without adequate biliary drainage,&#xD;
&#xD;
          2. Allograft recipient,&#xD;
&#xD;
          3. Active HBV (hepatitis B virus), HCV (hepatitis C virus ), or HIV infection, Note:&#xD;
             Patients with past HBV infection or resolved HBV infection (defined as having a&#xD;
             negative HBsAg test and a positive HBc (hepatitis B core antigen) antibody test are&#xD;
             eligible.&#xD;
&#xD;
             Note: Patients positive for HCV antibody are eligible only if polymerase chain&#xD;
             reaction testing is negative for HCV ribonucleic acid (RNA).&#xD;
&#xD;
          4. Diagnosis of any second malignancy within the last 5 years, except for adequately&#xD;
             treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix&#xD;
             uteri,&#xD;
&#xD;
          5. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the&#xD;
             exception of neuropathy, alopecia, and the laboratory values defined in the inclusion&#xD;
             criteria,&#xD;
&#xD;
          6. Known active central nervous system metastases and/or carcinomatous meningitis;&#xD;
             patients with previously treated brain metastases may participate provided they are&#xD;
             stable (without evidence of progression by imaging for at least 4 weeks prior to the&#xD;
             first dose of trial treatment and any neurological symptoms have returned to&#xD;
             baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids at a dose &gt; 10 mg/day of prednisone or equivalent for at least 14 days prior&#xD;
             to trial treatment,&#xD;
&#xD;
          7. Uncontrolled massive pleural effusion or massive ascites,&#xD;
&#xD;
          8. Evidence of interstitial lung disease, any active, non-infectious pneumonitis, or&#xD;
             known active tuberculosis,&#xD;
&#xD;
          9. Active uncontrolled infection, or current unstable or uncompensated respiratory or&#xD;
             cardiac conditions, or bleeding,&#xD;
&#xD;
         10. Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
             with the requirements of the study,&#xD;
&#xD;
         11. History or current evidence of any condition, therapy, or laboratory abnormality that&#xD;
             might confound the results of the trial, interfere with participation for the full&#xD;
             duration of the trial, or is not in the best interest of the participant, in the&#xD;
             opinion of the treating investigator,&#xD;
&#xD;
         12. Known or suspected drug hypersensitivity to OSE2101 vaccine,&#xD;
&#xD;
         13. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of&#xD;
             radiation within 4 weeks of the first dose of study drug,&#xD;
&#xD;
         14. Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of investigational product, Note: Local surgery of isolated lesions for&#xD;
             palliative intent is acceptable.&#xD;
&#xD;
         15. Treatment with any investigational medicinal product within 28 days prior to study&#xD;
             entry,&#xD;
&#xD;
         16. Prior intolerance/severe toxicity with 5-fluorouracil (5-FU) or irinotecan (including&#xD;
             dihydropyrimidinedehydrogenase [DPD] and UGT1A1 deficiency),&#xD;
&#xD;
         17. Pregnancy/lactation,&#xD;
&#xD;
         18. Tutelage or guardianship.&#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>Cindy NEUZILLET, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Curie site de Saint Cloud</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Cindy NEUZILLET, MD</last_name>
    <phone>0140298500</phone>
    <email>cindy.neuzillet@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marie-Line GARCIA LARNICOL, MD</last_name>
    <phone>0140298500</phone>
    <email>marie-line.garcia-larnicol@gercor.com.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Clinique de l'Europe</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Khadija KALAI, MD</last_name>
    </contact>
    <investigator>
      <last_name>Khadija KALAI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Sud CHU Amiens</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Vincent HAUTEFEUILLE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Vincent HAUTEFEUILLE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Beauvais</name>
      <address>
        <city>Beauvais</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Hocine FAYCAL, MD</last_name>
    </contact>
    <investigator>
      <last_name>Hocine FAYCAL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Jean Minjoz</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christophe BORG, MD</last_name>
    </contact>
    <investigator>
      <last_name>Christophe BORG, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinique Tivoli Ducos</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nathalie BONICHON LAMICHHANE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Nathalie BONICHON LAMICHHANE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Morvan</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jean Philippe METGES, MD</last_name>
    </contact>
    <investigator>
      <last_name>Jean Philippe METGES, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>GHPSO Site de Creil</name>
      <address>
        <city>Creil</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Elisabeth CAROLA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Elisabeth CAROLA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Henri Mondor</name>
      <address>
        <city>Créteil</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Isabelle BAUMGAERTNER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Isabelle BAUMGAERTNER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>François GHIRINGHELLI, MD</last_name>
    </contact>
    <investigator>
      <last_name>François GHIRINGHELLI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Dijon</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Antoine DROUILLARD, MD</last_name>
    </contact>
    <investigator>
      <last_name>Antoine DROUILLARD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Lille</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Anthony TURPIN, MD</last_name>
    </contact>
    <investigator>
      <last_name>Anthony TURPIN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christelle de LA FOUCHARDIERE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Christelle de LA FOUCHARDIERE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Julien FORESTIER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Julien FORESTIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital la Croix Rousse</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Marielle GUILLET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marielle GUILLET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Lyon Sud Hospices Civils de Lyon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Marion CHAUVENET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marion CHAUVENET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Privé Jean Mermoz</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jérôme DESRAME, MD</last_name>
    </contact>
    <investigator>
      <last_name>Jérome DESRAME, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yves RINALDI, MD</last_name>
    </contact>
    <investigator>
      <last_name>Yves RINALDI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Paoli Calmette</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Marine GILABERT, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marine GILABERT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Pitié Salpêtrière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jean Baptiste BACHET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Jean Baptiste BACHET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Antoine</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Isabelle TROUILLOUD, MD</last_name>
    </contact>
    <investigator>
      <last_name>Isabelle TROUILLOUD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Mutualiste Montsouris</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christophe LOUVET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Christophe LOUVET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Poitiers</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>David TOUGERON, MD</last_name>
    </contact>
    <investigator>
      <last_name>David TOUGERON, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Robert Debré</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Olivier BOUCHE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Olivier BOUCHE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Saint-Cloud</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cindy NEUZILLET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Cindy NEUZILLET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Paul Strauss</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Meher Ben Abdelghani, MD</last_name>
    </contact>
    <investigator>
      <last_name>Meher Ben Abdelghani, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinique Pasteur</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alain GRATET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Alain GRATET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital TROUSSEAU</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Thierry LECOMTE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Thierry LECOMTE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Insitut de Cancérologie de Lorraine</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Aurélien LAMBERT, MD</last_name>
    </contact>
    <investigator>
      <last_name>Aurélien LAMBERT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 24, 2018</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>February 24, 2023</last_update_submitted>
  <last_update_submitted_qc>February 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>Chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03806309
org study id: TEDOPAM D17-01 PRODIGE 63
nct id: NCT03806309
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
TEDOPAM is a randomized (1.1.1) non-comparative phase II study. This study will assess the
      efficacy and safety of OSE2101 alone or in combination with nivolumab followed by FOLFIRI
      reintroduction, versus FOLFIRI as maintenance therapy in patients with advanced PDAC after
      induction therapy with FOLFIRINOX.
Current standard of care for patients with advanced pancreatic ductal adenocarcinoma (PDAC)
      is chemotherapy, preferential regimen being FOLFIRINOX (5FU, leucovorin, irinotecan, and
      oxaliplatin) in fit patients (PS 0-1, bilirubin < 1.5 ULN). The question of how and when the
      FOLFIRINOX regimen and doses can be deescalated after a period of disease control (i.e.
      maintenance therapy) remains unanswered. In routine practice, oxaliplatin is usually stopped
      after 6-8 cycles due to limiting neuropathy, and the fluoropyrimidine is continued, either
      alone or, more frequently, in combination with irinotecan (FOLFIRI regimen), until disease
      progression.

      Immune therapies have opened new opportunities in cancer therapy. However, results of
      immunotherapy in PDAC have been disappointing so far, with failure of checkpoint inhibitor
      monotherapies (anti-CTLA4 and anti-PD-L1 monoclonal antibodies [mAb]) in progressive advanced
      PDAC, while monovalent vaccines were demonstrated to be safe but with limited activity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival (OS)
time frame: At 12 months
description: The OS is defined according to the DATECAN (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) consensus as the time from randomization to death for any reason. In the absence of confirmation of death, survival time will be censored at the date of the last clinical assessment
measure: Progression free survival (PFS) by centralized review of CT-scan imaging.
time frame: assessed up to 60 months
description: The PFS is defined according to the DATECAN consensus as the time from randomization to first progression or death for any reason, whichever occurs first. In the absence of event (confirmation of progression or death), PFS status will be censored at the date of the last radiological assessment.
PFS according to RECIST (Response Evaluation Criteria In Solid Tumors) v1.1 in the FOLFIRI arm (Arm A) and iRECIST (immune Response Evaluation Criteria In Solid Tumors) in the immune therapy arms (Arm B and C) by centralized review of CT-scan imaging
measure: Rate of patients with success of the strategy (SSR)
time frame: At 6 months
description: The SSR is derived from the duration of disease control (DDC), which is defined as the PFS, or, if FOLFIRI is reintroduced and achieves partial response (PR) or stable disease (SD), as the addition of the initial PFS (PFS1) and the PFS of the reintroduction PFS (PFS2)
measure: Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCICTCAE] v5.0
time frame: from signature of informed consent to 28 days after the last administration of the investigational product in Arm A and B and 100 days after the last administration of the investigational product in Arm C.
description: All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
measure: Objective response rate (ORR)
time frame: assessed up to 60 months
description: Response according to RECIST v1.1 in the FOLFIRI arm (Arm A) and iRECIST in the immune therapy arms (Arms B and C) (centralized review of CT-scan imaging); a comparative analysis of tumor response according to these two evaluation rules will be performed in Arm B and C
measure: Health-related Quality of life (HRQoL) evaluation assessed by EORTC QLQ (quality of life questionnaire) -C30 questionnaire
time frame: Baseline, Month 2, Month 4, Month 6, Month 8, Month 10, Month 12, Month 14, Month 16, Month 18, Month 20, Month 22, Month 24 (until the date of first documented progression or date of death, assessed up 60 months)
description: Rate of patients with an improvement of their quality of life score according to EORTC QLQ-C30. A quality of life score is obtained according to the answers to the 30 questions. The Minimal Clinically Important Difference (MCID) will be fixed to 10 points.
measure: Estimate the Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment (Q-Twist) for each participant
time frame: assessed up to 60 months
description: Q-TWiST analysis considers three health states, TOX (toxicity), TWiST, and REL (The duration of the relapse), and the duration of each state is calculated for every patient.
The TOX state comprises the total number of days after randomisation and before strategy failure spent with toxicity, regardless of when the toxicity started or whether there were gaps between toxicities. All grade 3 or 4 toxicities attributable to the study drugs are included in the analysis, apart from those starting after strategy failure.
The TWiST state is defined as DDC time minus time with toxicities.
The duration of the relapse or REL state is defined as OS time minus DDC time, or the period of time from progression to death. Patients alive at the end of the study are censored for the OS endpoint.
arm group label: Arm A : maintenance with FOLFIRI
arm group type: Active Comparator
description: FOLFIRI (IV; folinic acid 400 mg/m^2, irinotecan 180 mg/m^2, 5-FU bolus 400 mg/m^2 and continuous infusion 2,400 mg/m^2/46h (dose adjustment will be accepted).
arm group label: Arm B : maintenance with OSE2101 plus FOLFIRI
arm group type: Experimental
description: OSE2101 - subcutaneous injection on day 1 and day 15, every 4 weeks for 6 doses then every 8 weeks until month 12 then every 12 weeks up to 24 months.
FOLFIRI - schedules as in Arm A until disease progression on unacceptable toxicity
intervention type: Drug
intervention name: FOLFIRI
description: Intravenous (IV); folinic acid 400 mg/m^2, irinotecan 180 mg/m^2, 5-FU bolus 400 mg/m^2 and continuous infusion 2,400 mg/m^2
arm group label: Arm A : maintenance with FOLFIRI
arm group label: Arm B : maintenance with OSE2101 plus FOLFIRI
other name: Leucovorin (Folinic Acid), Fluorouracil, Irinotecan
intervention type: Drug
intervention name: OSE2101
description: subcutaneous injection on days 1 and 15, every 4 weeks for 6 doses then every 8 weeks until month 12 and then every 12 weeks for a maximum treatment duration of 24 months
arm group label: Arm B : maintenance with OSE2101 plus FOLFIRI
other name: Tedopi
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Cindy NEUZILLET, MD
role: Principal Investigator
affiliation: Institut Curie site de Saint Cloud
last name: Cindy NEUZILLET, MD
phone: 0140298500
email: cindy.neuzillet@gmail.com
last name: Marie-Line GARCIA LARNICOL, MD
phone: 0140298500
email: marie-line.garcia-larnicol@gercor.com.fr
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Irinotecan
sharing ipd: No