<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/NCT02999087</url>
  </required_header>
  <id_info>
    <org_study_id>GORTEC 2017-01</org_study_id>
    <nct_id>NCT02999087</nct_id>
  </id_info>
  <brief_title>Randomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)</brief_title>
  <acronym>REACH</acronym>
  <official_title>A Phase III Randomized Trial of Avelumab-cetuximab-Radiotherapy Versus Standards of Care in Locally Advanced Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Groupe Oncologie Radiotherapie Tete et Cou</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>UNICANCER</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Groupe Oncologie Radiotherapie Tete et Cou</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>
      The purpose of this study is to demonstrate that treatment with avelumab in combination with&#xD;
      RT-cetuximab is superior to standard of care (SOC) cisplatin-RT and/or to SOC RT-cetuximab&#xD;
      alone in terms of progression-free survival (PFS) in front-line patients with locally&#xD;
      advanced SCCHN.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This open-label, randomized, controlled, multicenter phase III study will include 688&#xD;
      patients with LA SCCHN (420 fit for HD cisplatin and 268 unfit for HD cisplatin),&#xD;
      histologically confirmed who had not received previous treatment for this setting. The study&#xD;
      is designed with the primary objective of demonstrating that treatment with avelumab in&#xD;
      combination with cetuximab-RT is superior to SOC Cisplatin-RT or cetuximab-RT alone in terms&#xD;
      of PFS. Randomization will assign the 2 treatment arms of each cohort with a 1:1 ratio. In&#xD;
      each cohort (fit for cisplatin and unfit for cisplatin), the randomization will be stratified&#xD;
      for the 2 most established prognostic factors N stage (N0-N1 vs N2-3) and p16 expression (OPC&#xD;
      p16+ versus OPC p16- or non OPC). All patients will be followed until death or at least 60&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 14, 2017</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">December 2027</primary_completion_date>
  <phase>Phase 3</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>Progression free survival</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 74 months</time_frame>
    <description>Time between randomization and the first event among progression (per modified Response Evaluation Criteria in Solid Tumors (RECIST) version v1.1) and death, whatever the cause of death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 74 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety: acute adverse events graded by NCI CTCAE v4.03</measure>
    <time_frame>From date of randomization to end of study, assessed up to 74 months</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">707</enrollment>
  <condition>HNSCC</condition>
  <arm_group>
    <arm_group_label>Arm A Patient FIT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lead-in phase (Day-8) : no treatment&#xD;
Concomitant radiotherapy phase : Radiotherapy by IMRT + cisplatin 100mg/m2&#xD;
Maintenance phase : no treatment until follow-up phase</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B Patient FIT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg&#xD;
Concomitant radiotherapy phase : Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg&#xD;
Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C Patient UNFIT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg&#xD;
Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg&#xD;
Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm D Patient UNFIT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lead-in phase (Day-8): Cetuximab 400mg/m2&#xD;
Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2&#xD;
Maintenance phase : no treatment until follow-up phase</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of RT.</description>
    <arm_group_label>Arm B Patient FIT</arm_group_label>
    <arm_group_label>Arm C Patient UNFIT</arm_group_label>
    <arm_group_label>Arm D Patient UNFIT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>avelumab</intervention_name>
    <description>IV infusion of avelumab (10 mg/kg over 1 hour) once every 2 weeks. Avelumab will start on Day-8 together with cetuximab and subsequently every 2 weeks during the course of RT. Avelumab with be continued every 2 weeks for an additional 12 months following RT.</description>
    <arm_group_label>Arm B Patient FIT</arm_group_label>
    <arm_group_label>Arm C Patient UNFIT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>100 mg/m² IV after hyperhydration and at a maximal rate of 1 mg/min, on days 1, 22, 43.</description>
    <arm_group_label>Arm A Patient FIT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>IMRT</intervention_name>
    <description>RT will be performed using IMRT (intensity modulated radiotherapy), with a simultaneous integrated boost (SIB) technique. RT dose to the GTV will be 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions). Prophylactic dose will be 52.8 Gy in 1.6 Gy daily fractions over 6.5 weeks (33 fractions).</description>
    <arm_group_label>Arm A Patient FIT</arm_group_label>
    <arm_group_label>Arm B Patient FIT</arm_group_label>
    <arm_group_label>Arm C Patient UNFIT</arm_group_label>
    <arm_group_label>Arm D Patient UNFIT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≤ 80 years&#xD;
&#xD;
          2. Performance Status ECOG 0-1&#xD;
&#xD;
          3. Squamous cell carcinoma, previously untreated&#xD;
&#xD;
          4. Stage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)&#xD;
&#xD;
          5. Oral cavity, oropharynx, hypopharynx or larynx&#xD;
&#xD;
          6. Availability of pre-treatment tumour tissue sample (for p16 &amp; PD -L1 expression, TILs&#xD;
             and immune landscape)&#xD;
&#xD;
          7. Recording of alcohol consumption and smoking history&#xD;
&#xD;
          8. Determination of the patient's ability to receive cisplatin 100 mg /m2 for 3 cycles&#xD;
             (fit / unfit)*&#xD;
&#xD;
          9. Written informed consent&#xD;
&#xD;
               -  Criteria for determining if a patient is fit for receiving high dose cisplatin:&#xD;
&#xD;
                    -  Calculated creatinin clearance ≥ 60 mL/min as determined by the modified.&#xD;
                       method of Cockcroft and Gault or by the EDTA method&#xD;
&#xD;
                    -  Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, hemoglobin ≥ 10&#xD;
                       g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the&#xD;
                       upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum&#xD;
                       albumin &gt; 35 g/L&#xD;
&#xD;
                    -  Peripheral neuropathy &lt; grade 2&#xD;
&#xD;
                    -  No clinical hearing loss (confirmed by audiogram)&#xD;
&#xD;
                    -  Cardiac function compatible with hyperhydration; Left ventricular ejection&#xD;
                       fraction within the institutional normal ranges as measured by&#xD;
                       echocardiogram&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers&#xD;
&#xD;
          2. Squamous cell carcinoma involving cervical neck nodes with unknown primary site&#xD;
&#xD;
          3. Metastatic disease (stage IVc)&#xD;
&#xD;
          4. Viral infection (HIV, Hepatitis B/C)&#xD;
&#xD;
          5. Autoimmune disease&#xD;
&#xD;
          6. Immunodeficiency or immunosuppressive therapy&#xD;
&#xD;
          7. Active CNS disease&#xD;
&#xD;
          8. Interstitial lung disease&#xD;
&#xD;
          9. Active infection&#xD;
&#xD;
         10. Any prior or current treatment for invasive head and neck cancer. This will include&#xD;
             but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody,&#xD;
             induction chemotherapy, prior surgical resection or RT, or use of any investigational&#xD;
             agent&#xD;
&#xD;
         11. Weight loss of &gt; 10% during the last 4 weeks (except if renutrition with a feeding&#xD;
             tube is planned before the onset of treatment or is ongoing)&#xD;
&#xD;
         12. Concurrent treatment with any other systemic anti-cancer therapy that is not specified&#xD;
             in the protocol&#xD;
&#xD;
         13. Concomitant treatment with any drug on the prohibited medication list such as live&#xD;
             vaccines&#xD;
&#xD;
         14. History of other malignancy within the last 3 years (exception of in situ carcinoma&#xD;
             and skin carcinomas)&#xD;
&#xD;
         15. Significant disease which, in the judgment of the investigator, as a result of the&#xD;
             medical interview, physical examinations, or screening investigations would make the&#xD;
             patient inappropriate for entry into the trial&#xD;
&#xD;
         16. Known hypersensitivity reaction to study drugs&#xD;
&#xD;
         17. Any social, personal, medical and/or psychological factor(s) that could interfere with&#xD;
             the observance of the patient to the protocol and/or the follow-up and/or the&#xD;
             signature of the informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Centre Hospitalier Bretagne Sud</name>
      <address>
        <city>Lorient</city>
        <zip>56322</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>June 19, 2023</last_update_submitted>
  <last_update_submitted_qc>June 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Head and Neck cancer</keyword>
  <keyword>Immunotherapy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</mesh_term>
    <mesh_term>Avelumab</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/NCT02999087
org study id: GORTEC 2017-01
nct id: NCT02999087
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to demonstrate that treatment with avelumab in combination with
      RT-cetuximab is superior to standard of care (SOC) cisplatin-RT and/or to SOC RT-cetuximab
      alone in terms of progression-free survival (PFS) in front-line patients with locally
      advanced SCCHN.
This open-label, randomized, controlled, multicenter phase III study will include 688
      patients with LA SCCHN (420 fit for HD cisplatin and 268 unfit for HD cisplatin),
      histologically confirmed who had not received previous treatment for this setting. The study
      is designed with the primary objective of demonstrating that treatment with avelumab in
      combination with cetuximab-RT is superior to SOC Cisplatin-RT or cetuximab-RT alone in terms
      of PFS. Randomization will assign the 2 treatment arms of each cohort with a 1:1 ratio. In
      each cohort (fit for cisplatin and unfit for cisplatin), the randomization will be stratified
      for the 2 most established prognostic factors N stage (N0-N1 vs N2-3) and p16 expression (OPC
      p16+ versus OPC p16- or non OPC). All patients will be followed until death or at least 60
      months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 74 months
description: Time between randomization and the first event among progression (per modified Response Evaluation Criteria in Solid Tumors (RECIST) version v1.1) and death, whatever the cause of death.
measure: Overall survival
time frame: From date of randomization until the date of death from any cause, assessed up to 74 months
measure: Safety: acute adverse events graded by NCI CTCAE v4.03
time frame: From date of randomization to end of study, assessed up to 74 months
arm group label: Arm A Patient FIT
arm group type: Active Comparator
description: Lead-in phase (Day-8) : no treatment
Concomitant radiotherapy phase : Radiotherapy by IMRT + cisplatin 100mg/m2
Maintenance phase : no treatment until follow-up phase
arm group label: Arm B Patient FIT
arm group type: Experimental
description: Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg
Concomitant radiotherapy phase : Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg
Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months
arm group label: Arm C Patient UNFIT
arm group type: Experimental
description: Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg
Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg
Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months
arm group label: Arm D Patient UNFIT
arm group type: Active Comparator
description: Lead-in phase (Day-8): Cetuximab 400mg/m2
Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2
Maintenance phase : no treatment until follow-up phase
intervention type: Drug
intervention name: Cetuximab
description: Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of RT.
arm group label: Arm B Patient FIT
arm group label: Arm C Patient UNFIT
arm group label: Arm D Patient UNFIT
intervention type: Drug
intervention name: avelumab
description: IV infusion of avelumab (10 mg/kg over 1 hour) once every 2 weeks. Avelumab will start on Day-8 together with cetuximab and subsequently every 2 weeks during the course of RT. Avelumab with be continued every 2 weeks for an additional 12 months following RT.
arm group label: Arm B Patient FIT
arm group label: Arm C Patient UNFIT
intervention type: Drug
intervention name: Cisplatin
description: 100 mg/m² IV after hyperhydration and at a maximal rate of 1 mg/min, on days 1, 22, 43.
arm group label: Arm A Patient FIT
intervention type: Radiation
intervention name: IMRT
description: RT will be performed using IMRT (intensity modulated radiotherapy), with a simultaneous integrated boost (SIB) technique. RT dose to the GTV will be 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions). Prophylactic dose will be 52.8 Gy in 1.6 Gy daily fractions over 6.5 weeks (33 fractions).
arm group label: Arm A Patient FIT
arm group label: Arm B Patient FIT
arm group label: Arm C Patient UNFIT
arm group label: Arm D Patient UNFIT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Cetuximab
mesh term: Avelumab
sharing ipd: No