<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/NCT04445064</url>
  </required_header>
  <id_info>
    <org_study_id>HN1901</org_study_id>
    <nct_id>NCT04445064</nct_id>
  </id_info>
  <brief_title>Activity and Safety of Peptide-based Immunotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck.</brief_title>
  <acronym>HN1901</acronym>
  <official_title>Activity and Safety of Peptide-based Immunotherapy in an Umbrella Window-of-opportunity Phase II Study in Patients With Squamous Cell Carcinoma of the Head and Neck.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</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 project is to realize a randomized open-label study (EudraCT number:&#xD;
      2020-000120-19) to evaluate the safety and the anti-tumor activity of peptide(s)-based&#xD;
      immunotherapy in an umbrella window pre-operative opportunity phase II study in patients with&#xD;
      squamous cell carcinoma of the head and neck.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with a head and neck squamous cell carcinoma eligible for curative treatment are&#xD;
      eligible for this proof of concept study. The included patients in arm A will receive IO102&#xD;
      subcutaneous at 100μg every week during the three weeks following the first endoscopy. The&#xD;
      included patients in am B (control group) won't receive any treatment. The included patients&#xD;
      in arm C will receive IO103 subcutaneous at 100μg every week during the three weeks following&#xD;
      the first endoscopy.&#xD;
&#xD;
      The main objectives of this study are:&#xD;
&#xD;
        -  To evaluate the T-cell peptide-specific response to the vaccine in a interferon(INF)-γ&#xD;
           ELISpot assay.&#xD;
&#xD;
        -  To assess the safety and tolerability of the vaccine.&#xD;
&#xD;
        -  To investigate the decreased action of the IDO enzyme in evaluating the increased&#xD;
           tumoral infiltration by CD8+ T-lymphocytes and by measuring the serum levels of&#xD;
           kynurenin, tryptophan,...&#xD;
&#xD;
        -  To evaluate the anti-tumor effect (objective response rate, overall survival, disease&#xD;
           free- survival, disease specific survival).&#xD;
&#xD;
        -  To evaluate the pre-operative activity of peptide vaccine using MRI (Magnetic Resonance&#xD;
           Imaging), DWI-MRI (Diffusion Weighted Imaging-MRI) and MRS (Magnetic Resonance&#xD;
           Spectroscopy) to visualize possible significant tumor modifications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Anticipated">June 8, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 8, 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>
    <intervention_model_description>Multicentric</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with a T-cell peptide-specific response to the vaccine as assessed by an interferon(INF)-γ ELISpot assay.</measure>
    <time_frame>2 years</time_frame>
    <description>ELISpot responses will be considered positive when the numbers of IFN-γ secreting cells will be at least twofold greater than the mean value of the baseline and with a minimum of 50 spots (per 5 × 10^5 peripheral blood mononuclear cell (PBMC) ) detected.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants experiencing toxicity</measure>
    <time_frame>2 years</time_frame>
    <description>Maximum grade of each toxicity and percentage of patients experiencing toxicity as assessed by CTC-NCIv5.0.&#xD;
Patients will have blood tests before the second and third administration of the vaccine and 4 weeks after surgery and clinical examinations before each administration of the vaccine and during the 3 months after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Increase in CD8+ T-cell density (cells/mm2) between tumour biopsies taken before and after treatment, as demonstrated by immunohistochemistry.</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>The length of time (in months) from the end of standard treatments during which patients are still alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) by RECIST Version 1.1</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival (DFS)</measure>
    <time_frame>2 years</time_frame>
    <description>The time (in months) from the end of the surgery to the time of first recurrence, death from any cause or last contact date, whichever occurred first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-specific survival (DSS)</measure>
    <time_frame>2 years</time_frame>
    <description>The time of survival (in months) of patients from the end of treatment to the date of death from a head and neck squamous cell carcinoma, or to the last follow-up date for patients still alive</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">17</enrollment>
  <condition>Oropharynx Squamous Cell Carcinoma</condition>
  <condition>Larynx Squamous Cell Carcinoma</condition>
  <condition>Hypopharynx Squamous Cell Carcinoma</condition>
  <condition>Oral Cavity Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm A: IO102 vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomization between arm A and B. Patients in arm A will receive IO102 3 to 4 times prior to curative treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Randomization between arm A and B</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C: IO103</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>No randomization. Patients in arm C will receive IO103 3 to 4 times prior to curative treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IO102</intervention_name>
    <description>100µg each week during the 3 weeks prior to curative treatment (total of 3 to 4 doses maximum)</description>
    <arm_group_label>Arm A: IO102 vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IO103</intervention_name>
    <description>100µg each week during the 3 weeks prior to curative treatment (total of 3 to 4 doses maximum)</description>
    <arm_group_label>Arm C: IO103</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women ≥ 18 years of age on day of signing informed consent.&#xD;
&#xD;
          2. Histologically proven squamous cell carcinoma of the oral cavity, oropharynx,&#xD;
             hypopharynx or larynx.&#xD;
&#xD;
          3. Patients selected for a surgical treatment.&#xD;
&#xD;
          4. No distant metastases.&#xD;
&#xD;
          5. Measurable disease as per RECIST 1.1.&#xD;
&#xD;
          6. No active second malignancy during the last 3 years except non melanomatous skin&#xD;
             cancer or carcinoma in situ of the cervix.&#xD;
&#xD;
          7. The participant provides written signed informed consent for the trial in accordance&#xD;
             with ICH-GCP and local legislation prior to admission to the trial.&#xD;
&#xD;
          8. Eastern Cooperative Oncology Group (ECOG) performance status scale 0-1 and Karnofsky&#xD;
             score &gt; or = 70.&#xD;
&#xD;
          9. Neutrophil count &gt; 1,500/mm3, platelet count &gt; 75,000/mm3, WBC&gt; or = 3.0/109 L,&#xD;
             bilirubin or creatinine &lt; 2 times ULN, ALT or AST &lt; 5 times ULN, Hemoglobin ≥ 9 g/dL.&#xD;
&#xD;
         10. A male participant able to father a child must agree to use contraception starting&#xD;
             with the screening visit and throughout the duration of the trial.&#xD;
&#xD;
         11. A female participant is eligible to participate if she is not pregnant not&#xD;
             breastfeeding, and at least one of the following conditions applies:&#xD;
&#xD;
               1. Not a woman of childbearing potential (WOCBP).&#xD;
&#xD;
               2. A WOCBP who agrees to follow contraceptive guidance starting with the screening&#xD;
                  and throughout the duration of the trial. WOCBP are allowed in the trial if they&#xD;
                  are using proper contraception (follow guidelines from the European Union Heads&#xD;
                  of Medicines Agency (CTFG, 2014).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Nasopharynx cancer, unknown primary and nasal cavity and paranasal sinuses carcinomas.&#xD;
&#xD;
          2. Previous exposure to immunotherapy.&#xD;
&#xD;
          3. Known diagnosis of immune deficiency or a positive serology of Human Immunodeficiency&#xD;
             Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
          4. Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative]&#xD;
             is detected) or pre-existing liver cirrhosis.&#xD;
&#xD;
          5. Other uncontrolled active illnesses or nonmalignant systemic disease (examples&#xD;
             include, but are not limited to, active infections requiring antibiotics, bleeding&#xD;
             disorders, uncontrolled diabetes, uncontrolled ventricular arrhythmia, uncontrolled&#xD;
             major seizure disorder, unstable spinal cord compression, superior vena cava&#xD;
             syndrome).&#xD;
&#xD;
          6. Has received a live vaccine within 30 days prior to the first dose of trial treatment&#xD;
&#xD;
          7. Has an active autoimmune disease that has required systemic treatment in past 2 years&#xD;
             (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency) is not considered a form&#xD;
             of systemic treatment and is allowed.&#xD;
&#xD;
          8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior the first dose of trial treatment.&#xD;
&#xD;
          9. Any psychiatric, psychological, familial, sociological or geographical condition&#xD;
             potentially hampering compliance with the study protocol and follow-up schedule.&#xD;
&#xD;
         10. Any malignancy (other than squamous cell carcinoma of the head and neck, non-melanoma&#xD;
             skin cancer or localized cervical cancer or localized and presumed cured prostatic&#xD;
             cancer or basal cell carcinoma of the skin and carcinoma in situ of the cervix or&#xD;
             bladder) within the last 3 years prior to registration.&#xD;
&#xD;
         11. Women of Child Bearing Potential (WOCBP) who has a positive urine pregnancy test&#xD;
             (e.g., within 72 hours) prior to treatment. If the urine test is positive or cannot be&#xD;
             confirmed as negative, a serum pregnancy test will be required.&#xD;
&#xD;
         12. Pregnant woman and women who are expecting to conceive.&#xD;
&#xD;
         13. Breastfeeding women.&#xD;
&#xD;
         14. Patients expected to father children within the projected duration of the trial.&#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>Jean-Pascal Machiels</last_name>
    <role>Principal Investigator</role>
    <affiliation>Insitut de Recherche Expérimentale et Clinique, pôle MIRO</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jean-Pascal Machiels</last_name>
    <phone>+3227645457</phone>
    <email>jean-pascal.machiels@uclouvain.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sandra Schmitz</last_name>
    <phone>+3227641881</phone>
    <email>sandra.schmitz@uclouvain.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Pascal Machiels</last_name>
      <phone>+3227645457</phone>
      <email>jean-pascal.machiels@uclouvain.be</email>
    </contact>
    <contact_backup>
      <last_name>Sandra Schmitz</last_name>
      <phone>+3227641881</phone>
      <email>sandra.schmitz@uclouvain.be</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>May 6, 2022</last_update_submitted>
  <last_update_submitted_qc>May 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vaccine</keyword>
  <keyword>immunotherapy</keyword>
  <keyword>squamous cell carcinoma</keyword>
  <keyword>head and neck</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>
  </condition_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/NCT04445064
org study id: HN1901
nct id: NCT04445064
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this project is to realize a randomized open-label study (EudraCT number:
      2020-000120-19) to evaluate the safety and the anti-tumor activity of peptide(s)-based
      immunotherapy in an umbrella window pre-operative opportunity phase II study in patients with
      squamous cell carcinoma of the head and neck.
Patients with a head and neck squamous cell carcinoma eligible for curative treatment are
      eligible for this proof of concept study. The included patients in arm A will receive IO102
      subcutaneous at 100μg every week during the three weeks following the first endoscopy. The
      included patients in am B (control group) won't receive any treatment. The included patients
      in arm C will receive IO103 subcutaneous at 100μg every week during the three weeks following
      the first endoscopy.

      The main objectives of this study are:

        -  To evaluate the T-cell peptide-specific response to the vaccine in a interferon(INF)-γ
           ELISpot assay.

        -  To assess the safety and tolerability of the vaccine.

        -  To investigate the decreased action of the IDO enzyme in evaluating the increased
           tumoral infiltration by CD8+ T-lymphocytes and by measuring the serum levels of
           kynurenin, tryptophan,...

        -  To evaluate the anti-tumor effect (objective response rate, overall survival, disease
           free- survival, disease specific survival).

        -  To evaluate the pre-operative activity of peptide vaccine using MRI (Magnetic Resonance
           Imaging), DWI-MRI (Diffusion Weighted Imaging-MRI) and MRS (Magnetic Resonance
           Spectroscopy) to visualize possible significant tumor modifications.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multicentric
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with a T-cell peptide-specific response to the vaccine as assessed by an interferon(INF)-γ ELISpot assay.
time frame: 2 years
description: ELISpot responses will be considered positive when the numbers of IFN-γ secreting cells will be at least twofold greater than the mean value of the baseline and with a minimum of 50 spots (per 5 × 10^5 peripheral blood mononuclear cell (PBMC) ) detected.
measure: Number of participants experiencing toxicity
time frame: 2 years
description: Maximum grade of each toxicity and percentage of patients experiencing toxicity as assessed by CTC-NCIv5.0.
Patients will have blood tests before the second and third administration of the vaccine and 4 weeks after surgery and clinical examinations before each administration of the vaccine and during the 3 months after surgery.
measure: Increase in CD8+ T-cell density (cells/mm2) between tumour biopsies taken before and after treatment, as demonstrated by immunohistochemistry.
time frame: 2 years
measure: Overall survival (OS)
time frame: 2 years
description: The length of time (in months) from the end of standard treatments during which patients are still alive.
measure: Objective response rate (ORR) by RECIST Version 1.1
time frame: 2 years
measure: Disease-free survival (DFS)
time frame: 2 years
description: The time (in months) from the end of the surgery to the time of first recurrence, death from any cause or last contact date, whichever occurred first
measure: Disease-specific survival (DSS)
time frame: 2 years
description: The time of survival (in months) of patients from the end of treatment to the date of death from a head and neck squamous cell carcinoma, or to the last follow-up date for patients still alive
arm group label: Arm A: IO102 vaccine
arm group type: Experimental
description: Randomization between arm A and B. Patients in arm A will receive IO102 3 to 4 times prior to curative treatment
arm group label: Arm B: Control group
arm group type: No Intervention
description: Randomization between arm A and B
arm group label: Arm C: IO103
arm group type: Experimental
description: No randomization. Patients in arm C will receive IO103 3 to 4 times prior to curative treatment
intervention type: Biological
intervention name: IO102
description: 100µg each week during the 3 weeks prior to curative treatment (total of 3 to 4 doses maximum)
arm group label: Arm A: IO102 vaccine
intervention type: Biological
intervention name: IO103
description: 100µg each week during the 3 weeks prior to curative treatment (total of 3 to 4 doses maximum)
arm group label: Arm C: IO103
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Pascal Machiels
role: Principal Investigator
affiliation: Insitut de Recherche Expérimentale et Clinique, pôle MIRO
last name: Jean-Pascal Machiels
phone: +3227645457
email: jean-pascal.machiels@uclouvain.be
last name: Sandra Schmitz
phone: +3227641881
email: sandra.schmitz@uclouvain.be
facility: 
status: Recruiting
contact: 
contact backup: 
country: Belgium
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck