<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/NCT03813836</url>
  </required_header>
  <id_info>
    <org_study_id>UCL/17/0396</org_study_id>
    <nct_id>NCT03813836</nct_id>
  </id_info>
  <brief_title>Phase II Trial of Pembrolizumab in Recurrent or Metastatic HNSCC</brief_title>
  <acronym>POPPY</acronym>
  <official_title>A Phase II Trial to Assess the Efficacy and Safety Profile of Pembrolizumab in Patients With Performance Status 2 With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University College, London</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>
      A single-arm phase II trial to assess the efficacy and safety profile of pembrolizumab in&#xD;
      patients with performance status of 2 with recurrent or metastatic squamous cell carcinoma of&#xD;
      the head and neck. Patients will receive best supportive care + pembrolizumab 200mg every 3&#xD;
      weeks for a maximum duration of 24 months&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 5, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2025</primary_completion_date>
  <phase>Phase 2</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>Disease control rate at 24 weeks assessed using iRECIST</measure>
    <time_frame>24 weeks after registration</time_frame>
    <description>Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate assessed using iRECIST</measure>
    <time_frame>12 months after registration</time_frame>
    <description>Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Response Rate- measured using the change from baseline tumour size. Assessed using iRECIST.</measure>
    <time_frame>6 months after registration</time_frame>
    <description>Best Response Rate, defined as proportion of patients who have a CR or PR as their best response, measured using the change from baseline tumour size, assessed using iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate -defined as patient's best response rate lasting at least 18 weeks</measure>
    <time_frame>From start of treatment to 30 months post start of treatment</time_frame>
    <description>Clinical Benefit Rate, defined as proportion patients who have achieved CR, PR or SD as their best response lasting at least 18 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response- defined as the time from first documented evidence of CR or PR until disease progression or death.</measure>
    <time_frame>From start of treatment to 30 months post start of treatment</time_frame>
    <description>Duration of Response, defined as the time from first documented evidence of CR or PR until disease progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression -defined as time from registration to the first documented disease progression</measure>
    <time_frame>From registration to 30 months post start of treatment</time_frame>
    <description>Time to Progression, defined as time from registration to the first documented disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first.</measure>
    <time_frame>From registration to 30 months post start of treatment</time_frame>
    <description>Progression Free Survival, defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival- defined as the time from registration to death due to any cause.</measure>
    <time_frame>From registration to 30 months post start of treatment</time_frame>
    <description>Overall Survival, defined as the time from registration to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and severity of adverse events- throughout the patient's treatment and until 6 months after completion of trial treatment.</measure>
    <time_frame>From date of registration until 6 months after completion of trial treatment</time_frame>
    <description>Frequency and severity of adverse events</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">65</enrollment>
  <condition>Metastatic Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Recurrent Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>pembrolizumab + best supportive care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Best supportive care and pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Patients will receive best supportive care + pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months</description>
    <arm_group_label>pembrolizumab + best supportive care</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head&#xD;
             and neck that is considered incurable by local therapies.&#xD;
&#xD;
          2. Measurable disease evaluated by RECIST v1.1&#xD;
&#xD;
          3. WHO performance status of 2&#xD;
&#xD;
          4. Life expectancy of at least 12 weeks&#xD;
&#xD;
          5. Aged ≥ 18 years of age&#xD;
&#xD;
          6. Adequate Bone marrow function:&#xD;
&#xD;
               -  Absolute neutrophils grade 0 or 1 (using CTCAE v5)&#xD;
&#xD;
               -  Platelets grade 0 or 1&#xD;
&#xD;
               -  Haemoglobin grade 0 or 1&#xD;
&#xD;
          7. Adequate renal function:&#xD;
&#xD;
             Creatinine grade 0 or 1 Calculated glomerular filtration rate (GFR) ≥ 50 mL/min&#xD;
             estimated using validated creatinine clearance calculation (e.g. Cockcroft-Gault or&#xD;
             Wright formula). If calculated GFR is &lt; 50 mL/min then an isotope GFR assessment&#xD;
             (Cr51-EDTA or 99mTc-DTPA) should be performed. If an isotope GFR test is unavailable&#xD;
             an estimation from 24 hour urine collection may be used&#xD;
&#xD;
          8. Adequate liver function:&#xD;
&#xD;
             Serum bilirubin grade 0 or 1 AST and ALT grade 0 or 1 (up to grade 2 for patients with&#xD;
             liver metastases)&#xD;
&#xD;
          9. Willing to use contraception for the duration of trial treatment and for 120 days&#xD;
             after completion of treatment&#xD;
&#xD;
         10. Willing to have a new biopsy, if site of disease is accessible and considered safe to&#xD;
             biopsy by investigator If newly obtained samples cannot be obtained (e.g. inaccessible&#xD;
             disease or patient safety concern) sites may submit archival tissue only upon&#xD;
             agreement from the sponsor&#xD;
&#xD;
         11. Able to give informed consent, indicating that the patient has been informed of and&#xD;
             understands the experimental nature of the study, possible risks and benefits, trial&#xD;
             procedures, and alternative options&#xD;
&#xD;
         12. Willing and able to comply with the protocol for the duration of the study, including&#xD;
             the treatment plan, investigations required and follow up visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with undifferentiated nasopharyngeal or sino-nasal cancers&#xD;
&#xD;
          2. Disease suitable for treatment with curative intent&#xD;
&#xD;
          3. Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent&#xD;
&#xD;
          4. Any investigational agents within 4 weeks prior to registration&#xD;
&#xD;
          5. Anti-cancer monoclonal antibody therapy within 4 weeks prior to registration&#xD;
&#xD;
          6. Chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to&#xD;
             registration&#xD;
&#xD;
          7. Patients with concurrent or previous malignancy that could compromise assessment of&#xD;
             the primary or secondary endpoints of the trial&#xD;
&#xD;
          8. Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment&#xD;
&#xD;
          9. Grade 3 or 4 peripheral neuropathy&#xD;
&#xD;
         10. Any serious and/or unstable pre-existing medical, psychiatric or other condition that,&#xD;
             in the treating clinician's judgment, could interfere with patient safety or obtaining&#xD;
             informed consent&#xD;
&#xD;
         11. Active central nervous system (CNS) metastases and/or carcinomatous meningitis;&#xD;
             subjects with previously treated brain metastases may participate provided they:&#xD;
&#xD;
             Are stable, without evidence of progression for at least four weeks prior to the first&#xD;
             dose of trial treatment Have no evidence of new or enlarging brain metastases Have no&#xD;
             evidence of leptomeningeal disease Are not using steroids for at least 7 days prior to&#xD;
             trial treatment&#xD;
&#xD;
         12. Has a known history of or is positive for hepatitis B (hepatitis B surface antigen&#xD;
             [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is&#xD;
             detected) NB: Without known history, testing is required to determine eligibility.&#xD;
             Hepatitis C antibody testing is allowed for screening purposes in sites where HCV RNA&#xD;
             is not part of standard of care&#xD;
&#xD;
         13. Immunocompromised patients (e.g. known HIV positive status)*&#xD;
&#xD;
         14. Prior organ transplantation including allogenic stem-cell transplantation&#xD;
&#xD;
         15. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required&#xD;
             steroids, or current pneumonitis/interstitial lung disease&#xD;
&#xD;
         16. Active infection requiring systemic therapy&#xD;
&#xD;
         17. Has received a live vaccine within 30 days prior to registration (seasonal flu&#xD;
             vaccines that do not contain live virus are permitted)&#xD;
&#xD;
         18. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment (NB: the use of physiologic doses of corticosteroids may be approved after&#xD;
             consultation with UCL CTC)&#xD;
&#xD;
         19. Active autoimmune disease that might deteriorate when receiving an immune-stimulatory&#xD;
             agent. Patients with the following are eligible:&#xD;
&#xD;
             Autoimmune-related hyperthyroidism or autoimmune-related hypothyroidism who are in&#xD;
             remission or on a stable dose of thyroid-replacement hormone Vitiligo Psoriasis&#xD;
&#xD;
         20. Current use of immunosuppressive medication, except for the following:&#xD;
&#xD;
        intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular&#xD;
        injection) Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisolone or&#xD;
        equivalent (after approval by UCL CTC) Steroids as premedication for hypersensitivity&#xD;
        reactions (e.g., CT scan premedication)&#xD;
&#xD;
        *Testing for HIV for the POPPY trial is not mandatory, however if this test has been done&#xD;
        the result should be known prior to registration.&#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>Martin Forster, FRCP PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University College, London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emily Ambrose</last_name>
    <phone>020 7679 9483</phone>
    <email>ctc.poppy@ucl.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rubina Begum</last_name>
    <phone>020 7679 9514</phone>
    <email>ctc.poppy@ucl.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Aberdeen Royal Infirmary (NHS Grampian)</name>
      <address>
        <city>Aberdeen</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Bristol Haematology and Oncology Centre (University Hospital Bristol NHS Foundation Trust)</name>
      <address>
        <city>Bristol</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Western General Hospital (NHS Lothian)</name>
      <address>
        <city>Edinburgh</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>East Suffolk and North Essex NHS Foundation Trust</name>
      <address>
        <city>Ipswich</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Guy's and St Thomas' NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University College London Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>East and North Hertfordshire NHS Trust</name>
      <address>
        <city>Northwood</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Queens Hospital (Barking, Havering and Redbridge University Hospitals NHS Trust)</name>
      <address>
        <city>Romford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Musgrove Park Hospital (Somerset NHS Foundation Trust)</name>
      <address>
        <city>Taunton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospital Trust</name>
      <address>
        <city>Truro</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Clatterbridge Cancer Centre NHS Foundation Trust</name>
      <address>
        <city>Wirral</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>June 8, 2023</last_update_submitted>
  <last_update_submitted_qc>June 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Head and Neck Cancer</keyword>
  <keyword>Metastatic Head and Neck Squamous Cell Carcinoma</keyword>
  <keyword>Recurrent Head and Neck Squamous Cell Carcinoma</keyword>
  <keyword>Pembrolizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03813836
org study id: UCL/17/0396
nct id: NCT03813836
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A single-arm phase II trial to assess the efficacy and safety profile of pembrolizumab in
      patients with performance status of 2 with recurrent or metastatic squamous cell carcinoma of
      the head and neck. Patients will receive best supportive care + pembrolizumab 200mg every 3
      weeks for a maximum duration of 24 months
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease control rate at 24 weeks assessed using iRECIST
time frame: 24 weeks after registration
description: Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST
measure: Disease control rate assessed using iRECIST
time frame: 12 months after registration
description: Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST
measure: Best Response Rate- measured using the change from baseline tumour size. Assessed using iRECIST.
time frame: 6 months after registration
description: Best Response Rate, defined as proportion of patients who have a CR or PR as their best response, measured using the change from baseline tumour size, assessed using iRECIST
measure: Clinical Benefit Rate -defined as patient's best response rate lasting at least 18 weeks
time frame: From start of treatment to 30 months post start of treatment
description: Clinical Benefit Rate, defined as proportion patients who have achieved CR, PR or SD as their best response lasting at least 18 weeks
measure: Duration of Response- defined as the time from first documented evidence of CR or PR until disease progression or death.
time frame: From start of treatment to 30 months post start of treatment
description: Duration of Response, defined as the time from first documented evidence of CR or PR until disease progression or death
measure: Time to Progression -defined as time from registration to the first documented disease progression
time frame: From registration to 30 months post start of treatment
description: Time to Progression, defined as time from registration to the first documented disease progression
measure: Progression Free Survival defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first.
time frame: From registration to 30 months post start of treatment
description: Progression Free Survival, defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first.
measure: Overall Survival- defined as the time from registration to death due to any cause.
time frame: From registration to 30 months post start of treatment
description: Overall Survival, defined as the time from registration to death due to any cause.
measure: Frequency and severity of adverse events- throughout the patient's treatment and until 6 months after completion of trial treatment.
time frame: From date of registration until 6 months after completion of trial treatment
description: Frequency and severity of adverse events
arm group label: pembrolizumab + best supportive care
arm group type: Experimental
description: Best supportive care and pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months
intervention type: Drug
intervention name: Pembrolizumab
description: Patients will receive best supportive care + pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months
arm group label: pembrolizumab + best supportive care
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martin Forster, FRCP PhD
role: Principal Investigator
affiliation: University College, London
last name: Emily Ambrose
phone: 020 7679 9483
email: ctc.poppy@ucl.ac.uk
last name: Rubina Begum
phone: 020 7679 9514
email: ctc.poppy@ucl.ac.uk
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: United Kingdom
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Recurrence
mesh term: Pembrolizumab