<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/NCT03777813</url>
  </required_header>
  <id_info>
    <org_study_id>UC-110/1719 -PRODIGE 67-UCGI33</org_study_id>
    <secondary_id>2018-000708-40</secondary_id>
    <nct_id>NCT03777813</nct_id>
  </id_info>
  <brief_title>Association of Radiochemotherapy and Immunotherapy for the Treatment of Unresectable Oesophageal caNcer</brief_title>
  <acronym>ARION</acronym>
  <official_title>Association of Radiochemotherapy and Immunotherapy for the Treatment of Unresectable Oesophageal caNcer: a Comparative Randomized Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNICANCER</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UNICANCER</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>
      This study aims to assess the efficacy of durvalumab in combination with radiochemotherapy&#xD;
      (FOLFOX and IMRT) and then as maintenance therapy for treating patients with localised&#xD;
      unresectable oesophageal cancer. This is a randomized, French national, multicentre,&#xD;
      comparative phase II trial&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ARION study will randomize 120 patients, in 12 centers in France, according to a ratio 1:1 in&#xD;
      the following arm of treatment:&#xD;
&#xD;
      - Standard and experimental arm:&#xD;
&#xD;
      Definitive modulated-intensity radiotherapy will be delivered according to boost integrated&#xD;
      technique 5 days a week for 5 weeks at a dose of:&#xD;
&#xD;
        -  50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused&#xD;
           FDG PET)&#xD;
&#xD;
        -  45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node&#xD;
&#xD;
      FOLFOX 4 simplified protocol, 1 infusion every 2 weeks (q2w) during 3 months starting with&#xD;
      radiotherapy (+/- 1 day):&#xD;
&#xD;
        -  IV oxaliplatin 85 mg/m² in 2 h on day 1 (D1)&#xD;
&#xD;
        -  IV Leucovorin 200 mg/m² in 2 h on D1, followed by&#xD;
&#xD;
        -  IV 5-FU 400 mg/m² in 10 minutes on D1 followed by&#xD;
&#xD;
        -  IV continuous infusion 5-FU 2400 mg/m² in 46 h&#xD;
&#xD;
        -  Experimental arm: Concomitant administration of durvalumab:&#xD;
&#xD;
      Every 4 weeks during concurrent FOLFOX (dose: 1500 mg) and after FOLFOX completion (total of&#xD;
      12 months of treatment).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 5, 2018</start_date>
  <completion_date type="Anticipated">September 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2024</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>cPFS (centrally reviewed cPFS)</measure>
    <time_frame>12-months cPFS</time_frame>
    <description>defined by a blinded independent centralized revue of progression free survival. cPFS is defined as the time from randomization until progression or death; patients alive and without documented progression at last follow-up news have PFS censored at this date or at initiation of new anticancer treatment (if applicable). Progression will be defined with central external reviewing of TDM per RECIST v1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>For each treatment arms, survival rates (PFS and OS) will be estimated at 12, 18 and 24 months</time_frame>
    <description>defined as the time between randomization and death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>2 years after randomization</time_frame>
    <description>will be assessed on occurrence of Adverse Events (AEs) based on NCI CTCAE v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life OES18, used for patients with oesophageal cancer always complemented by the QLQ-C30 measuring 5 functional scales (physical, everyday activity, cognitive, emotional and social) and 3 symptoms scales (fatigue, pain, nausea and vomiting)</measure>
    <time_frame>2 years after randomization</time_frame>
    <description>scores EORTC QLQ C30 - OES18</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Esophagus Cancer</condition>
  <condition>Unresectable Malignant Neoplasm</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Concomitant administration of durvalumab (dose: 1500 mg):&#xD;
Every 4 weeks during concurrent FOLFOX and after FOLFOX completion (total of 12 months of treatment)&#xD;
Definitive modulated-intensity radiotherapy will be delivered according to boost integrated technique 5 days a week for 5 weeks at a dose of:&#xD;
50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused FDG PET)&#xD;
45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node&#xD;
FOLFOX 4 simplified protocol, 1 infusion every 2 weeks during 3 months starting with radiotherapy (+/- 1 day):&#xD;
IV oxaliplatin 85 mg/m² in 2 h on D1&#xD;
IV Leucovorin 200 mg/m² in 2 h on D1, followed by&#xD;
IV 5-FU 400 mg/m² in 10 minutes on D1 followed by&#xD;
IV continuous infusion 5-FU 2400 mg/m² in 46 h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Definitive modulated-intensity radiotherapy will be delivered according to boost integrated technique 5 days a week for 5 weeks at a dose of:&#xD;
50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused FDG PET)&#xD;
45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node&#xD;
FOLFOX 4 simplified protocol, 1 infusion every 2 weeks during 3 months starting with radiotherapy (+/- 1 day):&#xD;
IV oxaliplatin 85 mg/m² in 2 h on D1&#xD;
IV Leucovorin 200 mg/m² in 2 h on D1, followed by&#xD;
IV 5-FU 400 mg/m² in 10 minutes on D1 followed by&#xD;
IV continuous infusion 5-FU 2400 mg/m² in 46 h</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Radiochemotherapy in standard arm and in experimental arm: 10 weeks (RT 50 Gy and FOLFOX q2w) Immunotherapy in experimental arm only: Patients will received concomitantly a maximum of 12 infusions</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)</intervention_name>
    <description>Radiochemotherapy in standard arm and in experimental arm: 10 weeks (RT 50 Gy and FOLFOX q2w)</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically proven squamous cell carcinoma or adenocarcinoma of the oesophagus,&#xD;
&#xD;
          2. Unresectable disease due to anatomical consideration or medical condition (patient&#xD;
             unfit for surgical procedure),&#xD;
&#xD;
          3. Presence of at least one measurable lesion &gt;10 mm with spiral CT scan,&#xD;
&#xD;
          4. No prior therapy for pathology investigated including chemotherapy or radiotherapy&#xD;
             prior to the study, except anterior out of field radiotherapy, received for treatment&#xD;
             of another primary tumor considered in remission, in the past 5 years,&#xD;
&#xD;
          5. Age ≥18 years old,&#xD;
&#xD;
          6. WHO performance status &lt;2 (i.e., 0 or 1),&#xD;
&#xD;
          7. Body weight &gt;35 kg,&#xD;
&#xD;
          8. Life expectancy of at least 12 weeks ,&#xD;
&#xD;
          9. Adequate haematology laboratory data within the 7 days before randomization&#xD;
&#xD;
               1. Absolute neutrophils &gt;1.5 x 109/L&#xD;
&#xD;
               2. Platelets &gt;100 x 109/L&#xD;
&#xD;
               3. Haemoglobin ≥9 g/dL,&#xD;
&#xD;
         10. Adequate Biochemistry laboratory data within the 7 days before randomization&#xD;
&#xD;
               1. Total bilirubin ≤1.5 x upper limit of normal (ULN)&#xD;
&#xD;
               2. Transaminases ≤2.5 x ULN&#xD;
&#xD;
               3. Alkaline phosphatases ≤5 x ULN,&#xD;
&#xD;
               4. Measured creatinine clearance (CL) &gt;40 mL/min by the Cockcroft-Gault formula,&#xD;
&#xD;
               5. Glycaemia ≤1.5 x ULN&#xD;
&#xD;
               6. Cholesterolaemia ≤7.30 mmol/L,&#xD;
&#xD;
               7. Albumin &gt;28 g/L&#xD;
&#xD;
         11. Adequate haemostasis laboratory data within 7 days prior to randomization: prothrombin&#xD;
             time (PT) within the normal range,&#xD;
&#xD;
         12. Adequate values for calcium, potassium and magnesium levels measured within 7 days&#xD;
             prior to randomization,&#xD;
&#xD;
         13. Women should be post-menopaused or willing to accept the use an effective&#xD;
             contraceptive regimen during the treatment period and for at least 6 months after the&#xD;
             end of the study. All non-menopausal women should have a negative pregnancy test&#xD;
             within 72 h prior to randomization. Men should accept to use an effective&#xD;
             contraception during treatment period and at least 6 months after the end of the study&#xD;
             especially after the last dose of oxaliplatin treatment.&#xD;
&#xD;
         14. Patients must have provided consent for the study by signing and dating a written&#xD;
             informed consent form prior to any study specific procedures, sampling, or analyses,&#xD;
&#xD;
         15. Patient affiliated to a social security regimen.&#xD;
&#xD;
         16. Uracilemia &lt; 16ng/ml&#xD;
&#xD;
         17. Forced expiratory volume (FEV) &gt;1 liter or &gt; 50% of the theoretical value&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with another PD-1, PD-L1 including durvalumab or CTLA-4 inhibitor&#xD;
&#xD;
          2. Metastatic disease,&#xD;
&#xD;
          3. Patients should not receive live vaccine 30 days prior to study drug&#xD;
&#xD;
          4. Female patients who are pregnant or breastfeeding&#xD;
&#xD;
          5. Uncontrolled intercurrent illness including, but not limited to diabetes,&#xD;
             hypertension, pulmonary failure, chronic renal or hepatic diseases, active peptic&#xD;
             ulcer disease or gastritis, active bleeding, diatheses... (non-exhaustive list),&#xD;
&#xD;
          6. Clinically significant cardiac disease or impaired cardiac function, such as:&#xD;
&#xD;
               1. Congestive heart failure requiring treatment (New York Heart Association [NYHA]&#xD;
                  grade ≥2), left ventricular ejection fraction (LVEF) &lt;50% as determined by&#xD;
                  multi-gated acquisition (MUGA) scan or echocardiogram (ECHO), or uncontrolled&#xD;
                  arterial hypertension defined by blood pressure &gt;140/100 mmHg at rest (average of&#xD;
                  3 consecutive readings),&#xD;
&#xD;
               2. History or current evidence of clinically significant cardiac arrhythmias, atrial&#xD;
                  fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome,&#xD;
                  high- grade/complete AV-blockage,&#xD;
&#xD;
               3. Acute coronary syndromes (including myocardial infarction, unstable angina,&#xD;
                  coronary artery bypass graft (CABG), coronary angioplasty, or stenting), &lt;3&#xD;
                  months prior to screening,&#xD;
&#xD;
               4. MeanQT interval corrected for heart rate (QTc) ≥470 ms calculated from 3&#xD;
                  electrocardiograms (ECGs) using Fridericia's Correction.&#xD;
&#xD;
          7. Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             administration of durvalumab (exception: systemic corticosteroids at physiologic doses&#xD;
             not exceeding 10 mg/day of prednisone or equivalent are allowed as well as steroids as&#xD;
             premedication for hypersensitivity reactions (e.g., CT scan premedication) - Topical,&#xD;
             inhaled, nasal, and ophthalmic steroids are allowed,&#xD;
&#xD;
          8. Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with&#xD;
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,&#xD;
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid&#xD;
             arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
               1. Patients with vitiligo or alopecia&#xD;
&#xD;
               2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stabilised with&#xD;
                  hormone replacement therapy&#xD;
&#xD;
               3. Any chronic skin condition that does not require systemic therapy&#xD;
&#xD;
               4. Patients without active disease in the last 5 years may be included but only&#xD;
                  after consultation with the study physician&#xD;
&#xD;
               5. Patients with coeliac disease controlled by diet alone&#xD;
&#xD;
          9. Known primary immunodeficiency or active HIV,&#xD;
&#xD;
         10. Patient with a dihydropyrimidine dehydrogenase (DPD) deficiency (Uracilemia ≥ 16&#xD;
             ng/ml, the test should be done for all patients before 5-FU administration)* ,&#xD;
&#xD;
         11. Known active or chronic viral hepatitis or history of any type of hepatitis within the&#xD;
             last 6 months indicated by positive HBS antibody test for hepatitis B or hepatitis C&#xD;
             virus ribonucleic acid (HCV antibody),&#xD;
&#xD;
         12. History of organ transplantation requiring the use of immunosuppressive medication,&#xD;
             including allogenic stem cell transplant&#xD;
&#xD;
         13. History of active tuberculosis or latent disease capable of reactivation,&#xD;
&#xD;
         14. Current pneumonitis or interstitial lung disease,&#xD;
&#xD;
         15. Other invasive malignancy within 2 years prior to entry into the study, except for&#xD;
             those treated with surgical therapy only,&#xD;
&#xD;
         16. History of severe allergic reactions or hypersensitivity to any unknown allergens or&#xD;
             any components of the study drug (refer to IB of durvalumab section 5.5.1.11).&#xD;
&#xD;
         17. Any prior corticosteroid-refractory immune-related adverse event (irAE),&#xD;
&#xD;
         18. Oeso-tracheal or oeso-bronchial fistulae,&#xD;
&#xD;
         19. Major surgery within 28 days prior to the first dose of study treatment&#xD;
&#xD;
         20. Toxicities of grade ≥1 from any previous therapy,&#xD;
&#xD;
         21. Peripheral sensory neuropathy with functional impairment&#xD;
&#xD;
         22. Severe infection requiring parenteral antibiotic treatment&#xD;
&#xD;
         23. Patients treated with sorivudine or analogues as brivudine&#xD;
&#xD;
         24. Patients treated with phenytoin for prophylaxis&#xD;
&#xD;
         25. Participation in another therapeutic trial within the 30 days prior to study&#xD;
             inclusion,&#xD;
&#xD;
         26. Patients deprived of liberty or under guardianship,&#xD;
&#xD;
         27. Patients unable to adhere to the protocol for geographical, social, or psychological&#xD;
             reasons.&#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>Anouchka Modesto, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Claudius Regaud</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Laurent Quero, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Saint Louis / Université Paris Diderot</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Veronica Pezzella</last_name>
    <phone>+33 (0)1 44 23 04 77</phone>
    <email>v-pezzella@unicancer.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laure Monard</last_name>
    <email>l-monard@unicancer.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centre Oscar Lambret, CLCC UNICANCER</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Farid EL HAJBI</last_name>
      <email>f-elhajbi@o-lambret.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Louis, APHP</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Laurent Quero</last_name>
      <email>laurent.quero@aphp.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpital Haut-Lévêque</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Véronique VENDRELY-BUTTIAUX</last_name>
      <email>veronique.vendrely@chu-bordeaux.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David TOUGERON</last_name>
      <email>david.tougeron@chu-poitiers.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Paul Strauss, CLCC UNICANCER</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Meher BEN ABDELGHANI</last_name>
      <email>mbenabdelghani@strasbourg.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Iuct, Clcc Unicancer</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anouchka Modesto</last_name>
      <phone>+33 (0) 5 31 15 54 28</phone>
      <email>Modesto.Anouchka@iuct-oncopole.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Rangueil Larrey</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rosine Guimbaud</last_name>
      <email>guimbaud.r@chu-toulouse.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>oesophagus</keyword>
  <keyword>localised unresectable</keyword>
  <keyword>adenocarcinoma or squamous cell carcinoma</keyword>
  <keyword>durvalumab</keyword>
  <keyword>FOLFOX 4 simplified</keyword>
  <keyword>Definitive modulated-intensity radiotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.</ipd_time_frame>
    <ipd_access_criteria>Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.</ipd_access_criteria>
  </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/NCT03777813
org study id: UC-110/1719 -PRODIGE 67-UCGI33
secondary id: 2018-000708-40
nct id: NCT03777813
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to assess the efficacy of durvalumab in combination with radiochemotherapy
      (FOLFOX and IMRT) and then as maintenance therapy for treating patients with localised
      unresectable oesophageal cancer. This is a randomized, French national, multicentre,
      comparative phase II trial
ARION study will randomize 120 patients, in 12 centers in France, according to a ratio 1:1 in
      the following arm of treatment:

      - Standard and experimental arm:

      Definitive modulated-intensity radiotherapy will be delivered according to boost integrated
      technique 5 days a week for 5 weeks at a dose of:

        -  50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused
           FDG PET)

        -  45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node

      FOLFOX 4 simplified protocol, 1 infusion every 2 weeks (q2w) during 3 months starting with
      radiotherapy (+/- 1 day):

        -  IV oxaliplatin 85 mg/m² in 2 h on day 1 (D1)

        -  IV Leucovorin 200 mg/m² in 2 h on D1, followed by

        -  IV 5-FU 400 mg/m² in 10 minutes on D1 followed by

        -  IV continuous infusion 5-FU 2400 mg/m² in 46 h

        -  Experimental arm: Concomitant administration of durvalumab:

      Every 4 weeks during concurrent FOLFOX (dose: 1500 mg) and after FOLFOX completion (total of
      12 months of treatment).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: cPFS (centrally reviewed cPFS)
time frame: 12-months cPFS
description: defined by a blinded independent centralized revue of progression free survival. cPFS is defined as the time from randomization until progression or death; patients alive and without documented progression at last follow-up news have PFS censored at this date or at initiation of new anticancer treatment (if applicable). Progression will be defined with central external reviewing of TDM per RECIST v1.1
measure: Overall survival (OS)
time frame: For each treatment arms, survival rates (PFS and OS) will be estimated at 12, 18 and 24 months
description: defined as the time between randomization and death due to any cause.
measure: Adverse Events
time frame: 2 years after randomization
description: will be assessed on occurrence of Adverse Events (AEs) based on NCI CTCAE v5.0
measure: Quality of Life OES18, used for patients with oesophageal cancer always complemented by the QLQ-C30 measuring 5 functional scales (physical, everyday activity, cognitive, emotional and social) and 3 symptoms scales (fatigue, pain, nausea and vomiting)
time frame: 2 years after randomization
description: scores EORTC QLQ C30 - OES18
arm group label: Arm A
arm group type: Experimental
description: Concomitant administration of durvalumab (dose: 1500 mg):
Every 4 weeks during concurrent FOLFOX and after FOLFOX completion (total of 12 months of treatment)
Definitive modulated-intensity radiotherapy will be delivered according to boost integrated technique 5 days a week for 5 weeks at a dose of:
50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused FDG PET)
45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node
FOLFOX 4 simplified protocol, 1 infusion every 2 weeks during 3 months starting with radiotherapy (+/- 1 day):
IV oxaliplatin 85 mg/m² in 2 h on D1
IV Leucovorin 200 mg/m² in 2 h on D1, followed by
IV 5-FU 400 mg/m² in 10 minutes on D1 followed by
IV continuous infusion 5-FU 2400 mg/m² in 46 h
arm group label: Arm B
arm group type: Active Comparator
description: Definitive modulated-intensity radiotherapy will be delivered according to boost integrated technique 5 days a week for 5 weeks at a dose of:
50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused FDG PET)
45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node
FOLFOX 4 simplified protocol, 1 infusion every 2 weeks during 3 months starting with radiotherapy (+/- 1 day):
IV oxaliplatin 85 mg/m² in 2 h on D1
IV Leucovorin 200 mg/m² in 2 h on D1, followed by
IV 5-FU 400 mg/m² in 10 minutes on D1 followed by
IV continuous infusion 5-FU 2400 mg/m² in 46 h
intervention type: Drug
intervention name: Durvalumab
description: Radiochemotherapy in standard arm and in experimental arm: 10 weeks (RT 50 Gy and FOLFOX q2w) Immunotherapy in experimental arm only: Patients will received concomitantly a maximum of 12 infusions
arm group label: Arm A
other name: IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)
intervention type: Combination Product
intervention name: IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)
description: Radiochemotherapy in standard arm and in experimental arm: 10 weeks (RT 50 Gy and FOLFOX q2w)
arm group label: Arm A
arm group label: Arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anouchka Modesto, Doctor
role: Principal Investigator
affiliation: Institut Claudius Regaud
last name: Laurent Quero, Doctor
role: Principal Investigator
affiliation: Hôpital Saint Louis / Université Paris Diderot
last name: Veronica Pezzella
phone: +33 (0)1 44 23 04 77
email: v-pezzella@unicancer.fr
last name: Laure Monard
email: l-monard@unicancer.fr
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Esophageal Neoplasms
mesh term: Leucovorin
mesh term: Oxaliplatin
mesh term: Durvalumab
mesh term: Levoleucovorin
sharing ipd: Yes
ipd description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
ipd access criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.