<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/NCT02997332</url>
  </required_header>
  <id_info>
    <org_study_id>2015-004146-25</org_study_id>
    <secondary_id>2015/2316</secondary_id>
    <nct_id>NCT02997332</nct_id>
  </id_info>
  <brief_title>Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU for Locally Advanced Head and Neck Squamous Cell Carcinoma</brief_title>
  <acronym>MEDINDUCTION</acronym>
  <official_title>Phase I Trial Evaluating the Safety of Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU in Induction for Locally Advanced Head and Neck Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gustave Roussy, Cancer Campus, Grand Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gustave Roussy, Cancer Campus, Grand Paris</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 prognosis of patients with locally advanced SCCHN is poor. Results of recent randomized&#xD;
      trials evaluating induction chemotherapy by docetaxel, cisplatin, 5 fluorouracil are&#xD;
      conflicting, and benefit on overall survival is uncertain. Improve efficacy of induction&#xD;
      chemotherapy is important without increase toxicities. Durvalumab is a promising agent in&#xD;
      SSCHN. The safety of combination of docetaxel, cisplatin, 5 fluorouracil with durvalumab is&#xD;
      unknown.&#xD;
&#xD;
      The aim of the study is to evaluate the feasibility and the safety of the association of DCF&#xD;
      (standard regimen for induction in SSCCHN) and durvalumab. The safety profile of DCF and&#xD;
      durvalumab are different, so the expected toxicities should not be additive. The addition of&#xD;
      durvalumab to DCF could improve the efficacy of induction chemotherapy and the prognostic of&#xD;
      patients with SSCCHN.&#xD;
&#xD;
      Concerning the translational research, the aim will be to explore the relationships between&#xD;
      immune capacity, specificity, activation state and clinical outcome to help elucidate the&#xD;
      determinants of response to immunotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 30, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <phase>Phase 1</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended Phase 2 dose (RP2D)</measure>
    <time_frame>Up to 10 weeks</time_frame>
    <description>To determine the recommended Phase 2 dose (RP2D) and schedule of durvalumab when administered with docetaxel, cisplatin and 5 Fluorouracil</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Dose Limiting Toxicity (DLT)</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>To characterize the safety and tolerability profile of durvalumab when administered in combination with docetaxel, cisplatin and 5 Fluorouracil</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Head and Neck Cancers</condition>
  <arm_group>
    <arm_group_label>Patients with squamous cell carcinoma of the oral cavity,</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The aim is to evaluate safety, PK and pharmacodynamics of durvalumab in adult patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx previously untreated, with indication of induction chemotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab will be administered every 3 weeks for 3 injections at week 1, 4, 7. Dose levels: the durvalumab first dose level is 1120 mg Q3W, and the dose level -1 is 750 mg Q3W.</description>
    <arm_group_label>Patients with squamous cell carcinoma of the oral cavity,</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel 75mg/m² on D2, IV in 1 hour</description>
    <arm_group_label>Patients with squamous cell carcinoma of the oral cavity,</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin 75mg/m² on D2, IV in 3 hours</description>
    <arm_group_label>Patients with squamous cell carcinoma of the oral cavity,</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5 Fluorouracil</intervention_name>
    <description>5 Fluorouracil 750mg/m²/day on D2, D3, D4, D5, D6 IV in 24 hours</description>
    <arm_group_label>Patients with squamous cell carcinoma of the oral cavity,</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years and &lt; 75 years&#xD;
&#xD;
          2. Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity,&#xD;
             oropharynx, larynx or hypopharynx, previously untreated, amenable to induction&#xD;
             chemotherapy according to the investigator. Patients with a diagnosis of SCCHN of&#xD;
             occult primary could be enrolled.&#xD;
&#xD;
          3. Absence of metastases determined by CT scan or PET scan&#xD;
&#xD;
          4. ECOG performance status &lt; 1&#xD;
&#xD;
          5. Subjects must have at least 1 measurable lesion per RECIST v1.1 guidelines&#xD;
&#xD;
          6. Adequate organ and marrow function as defined below:&#xD;
&#xD;
               -  Hemoglobin ≥ 9,0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500/mm3&#xD;
&#xD;
               -  Platelet count ≥ 100,000/mm3&#xD;
&#xD;
               -  AST and ALT ≤ 2.5 × institutional upper limit of normal (ULN);&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 × ULN;&#xD;
&#xD;
               -  Creatinine clearance &gt; 60 mL/min as determined by the Cockcroft-Gault equation&#xD;
                  (Cockcroft and Gault, 1976) or by 24-hour urine collection for determination of&#xD;
                  creatinine clearance&#xD;
&#xD;
          7. Negative serology for hepatitis B and C&#xD;
&#xD;
          8. Availability of a recent formalin-fixed tumour tissue (&lt; 3 months) to determine HPV&#xD;
             status and for translational research (IHC)&#xD;
&#xD;
             a. All patients without available tumour tissue will undergo a panendoscopy with&#xD;
             biopsies.&#xD;
&#xD;
          9. Women of childbearing potential must have a negative serum β-HCG pregnancy test within&#xD;
             7 days prior to the administration of the first study treatment and/or urine pregnancy&#xD;
             48 hours prior to the administration of the first study treatment. Both sexually&#xD;
             active women of childbearing potential and males (and their female partners) patients&#xD;
             must agree to use two methods of effective contraception, one of them being a barrier&#xD;
             method, or to abstain from sexual activity during the study and for at least 6 months&#xD;
             after last dose of study drugs.&#xD;
&#xD;
         10. Patients must be willing and able to comply with scheduled visits, treatment plan,&#xD;
             laboratory tests and other study procedures&#xD;
&#xD;
         11. Patients must be affiliated to a Social Security System or beneficiary of the same&#xD;
&#xD;
         12. Patient information and written informed consent form signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Primary site of head and neck carcinoma in nasopharynx, or skin&#xD;
&#xD;
          2. Patients receiving other anti-cancer medication such as, chemotherapy, immunotherapy,&#xD;
             biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other&#xD;
             than leuprolide or other GnRH agonists) or other investigational agent within 30 days&#xD;
             prior to the first dose of study drug and while on study treatment.&#xD;
&#xD;
          3. Patients receiving other anti-cancer non-drug therapies: radiation, or tumor&#xD;
             embolization within 30 days prior to the first dose of study drug and while on study&#xD;
             treatment.&#xD;
&#xD;
          4. No relevant toxicities (&gt;grade 1 CTCAE) due to prior medical treatment at time of&#xD;
             study entry&#xD;
&#xD;
          5. Participation in another clinical study with an investigational product during the&#xD;
             last 30 days&#xD;
&#xD;
          6. Patient with dihydropyrimidine dehydrogenase (DPD) deficiency&#xD;
&#xD;
          7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, active peptic ulcer disease or gastritis, active bleeding diatheses. Or&#xD;
             patient under guardianship or deprived of his liberty by a judicial or administrative&#xD;
             decision or any condition (e.g psychiatric illness/social/familial/geographical&#xD;
             condition) that would limit compliance with study requirement or compromise the&#xD;
             ability of the subject to give written informed consent&#xD;
&#xD;
          8. Patient with active cardiac disease or with a history of cardiac dysfunction any of&#xD;
             the following:&#xD;
&#xD;
               -  Left Ventricular Ejection Fraction (LVEF) &lt; 50% as determined by Multiple Gated&#xD;
                  acquisition (MUGA) scan or echocardiogram (ECHO),&#xD;
&#xD;
               -  Mean QT interval corrected for heart rate (QTc) ≥ 470 msec calculated from 3&#xD;
                  electrocardiograms (ECGs) performed at screening, using Fredericia's correction&#xD;
                  (QTcF),&#xD;
&#xD;
               -  Myocardial infarction within the last 6 months, documented by persistent elevated&#xD;
                  cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF&#xD;
                  function,&#xD;
&#xD;
               -  Unstable angina pectoris&#xD;
&#xD;
               -  Uncontrolled hypertension&#xD;
&#xD;
               -  History of documented congestive heart failure (New York Heart Association&#xD;
                  functional classification III-IV), or Uncontrolled symptomatic congestive heart&#xD;
                  failure&#xD;
&#xD;
               -  Documented cardiomyopathy,&#xD;
&#xD;
               -  Other cardiac arrhythmia not controlled with medication.&#xD;
&#xD;
          9. Other invasive malignancy within 5 years except for noninvasive malignancies such as&#xD;
             cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma&#xD;
             in situ of the breast that has/have been surgically cured&#xD;
&#xD;
         10. Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or&#xD;
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of&#xD;
             prednisone or an equivalent corticosteroid&#xD;
&#xD;
         11. Receipt of live attenuated vaccination within 30 days prior to study entry or within&#xD;
             30 days of receiving durvalumab&#xD;
&#xD;
         12. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects&#xD;
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within&#xD;
             the past 2 years) are not excluded&#xD;
&#xD;
         13. Active or prior documented inflammatory bowel disease (eg, Crohn's disease,ulcerative&#xD;
             colitis)&#xD;
&#xD;
         14. History of primary immunodeficiency&#xD;
&#xD;
         15. History of allogenic organ transplant that requires use of immunosuppressives&#xD;
&#xD;
         16. Known history of previous clinical diagnosis of tuberculosis&#xD;
&#xD;
         17. Patients with a known HIV status&#xD;
&#xD;
         18. Pregnant or breast-feeding women&#xD;
&#xD;
         19. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab&#xD;
&#xD;
         20. History of hypersensitivity to durvalumab or any excipients or to other humanized mAbs&#xD;
&#xD;
         21. Any contraindication to the use of cisplatin, docetaxel and 5FU and/or known history&#xD;
             of hypersensitivity to any of those drugs&#xD;
&#xD;
         22. Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of study treatment or interpretation of patient safety or study results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Caroline EVEN, MD</last_name>
    <phone>0142116537</phone>
    <phone_ext>+33</phone_ext>
    <email>caroline.even@gustaveroussy.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Matthieu TEXIER</last_name>
    <phone>0142116309</phone>
    <phone_ext>+33</phone_ext>
    <email>matthieu.texier@gustaveroussy.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <state>Val De Marne</state>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caroline EVEN, MD</last_name>
      <phone>0142116537</phone>
      <phone_ext>+33</phone_ext>
      <email>caroline.even@gustaveroussy.fr</email>
    </contact>
    <contact_backup>
      <last_name>Matthieu TEXIER</last_name>
      <phone>0142116309</phone>
      <phone_ext>+33</phone_ext>
      <email>matthieu.texier@gustaveroussy.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Durvalumab</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/NCT02997332
org study id: 2015-004146-25
secondary id: 2015/2316
nct id: NCT02997332
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The prognosis of patients with locally advanced SCCHN is poor. Results of recent randomized
      trials evaluating induction chemotherapy by docetaxel, cisplatin, 5 fluorouracil are
      conflicting, and benefit on overall survival is uncertain. Improve efficacy of induction
      chemotherapy is important without increase toxicities. Durvalumab is a promising agent in
      SSCHN. The safety of combination of docetaxel, cisplatin, 5 fluorouracil with durvalumab is
      unknown.

      The aim of the study is to evaluate the feasibility and the safety of the association of DCF
      (standard regimen for induction in SSCCHN) and durvalumab. The safety profile of DCF and
      durvalumab are different, so the expected toxicities should not be additive. The addition of
      durvalumab to DCF could improve the efficacy of induction chemotherapy and the prognostic of
      patients with SSCCHN.

      Concerning the translational research, the aim will be to explore the relationships between
      immune capacity, specificity, activation state and clinical outcome to help elucidate the
      determinants of response to immunotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended Phase 2 dose (RP2D)
time frame: Up to 10 weeks
description: To determine the recommended Phase 2 dose (RP2D) and schedule of durvalumab when administered with docetaxel, cisplatin and 5 Fluorouracil
measure: Number of Dose Limiting Toxicity (DLT)
time frame: Up to 6 weeks
description: To characterize the safety and tolerability profile of durvalumab when administered in combination with docetaxel, cisplatin and 5 Fluorouracil
arm group label: Patients with squamous cell carcinoma of the oral cavity,
arm group type: Experimental
description: The aim is to evaluate safety, PK and pharmacodynamics of durvalumab in adult patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx previously untreated, with indication of induction chemotherapy.
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab will be administered every 3 weeks for 3 injections at week 1, 4, 7. Dose levels: the durvalumab first dose level is 1120 mg Q3W, and the dose level -1 is 750 mg Q3W.
arm group label: Patients with squamous cell carcinoma of the oral cavity,
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel 75mg/m² on D2, IV in 1 hour
arm group label: Patients with squamous cell carcinoma of the oral cavity,
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin 75mg/m² on D2, IV in 3 hours
arm group label: Patients with squamous cell carcinoma of the oral cavity,
intervention type: Drug
intervention name: 5 Fluorouracil
description: 5 Fluorouracil 750mg/m²/day on D2, D3, D4, D5, D6 IV in 24 hours
arm group label: Patients with squamous cell carcinoma of the oral cavity,
criteria: 
gender: All
minimum age: 18 Years
maximum age: 74 Years
healthy volunteers: No
last name: Caroline EVEN, MD
phone: 0142116537
phone ext: +33
email: caroline.even@gustaveroussy.fr
last name: Matthieu TEXIER
phone: 0142116309
phone ext: +33
email: matthieu.texier@gustaveroussy.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Docetaxel
mesh term: Fluorouracil
mesh term: Durvalumab
sharing ipd: No