xml: <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/NCT05993858</url>
    </required_header>
    <id_info>
      <org_study_id>UHCT230527</org_study_id>
      <nct_id>NCT05993858</nct_id>
    </id_info>
    <brief_title>Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced HNSCC</brief_title>
    <acronym>PC-1</acronym>
    <official_title>A Single-Center, Single-Arm Exploratory Clinical Trial of Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced Head and Neck Squamous Cell Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Wuhan Union Hospital, China</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Wuhan Union Hospital, China</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a single-center, single-arm, phase II clinical study to evaluate the efficacy and&#xD;
        safety of PD-1 inhibitor combined with cetuximab in neoadjuvant therapy for locally advanced&#xD;
        HNSCC.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        At present, the standard treatment for patients with operable locally advanced head and neck&#xD;
        squamous cell carcinoma (HNSCC) is adjuvant radiotherapy with or without platinum-based&#xD;
        synchronous chemotherapy after operation. However, the risk of recurrence, metastasis and&#xD;
        death remains high in this population with this intense combination treatment regimen. Both&#xD;
        EGFR monoclonal antibody and PD-1 inhibitors have proven the effect in advanced HNSCC. At the&#xD;
        same time, cetuximab and PD-1 inhibitors have been reported to have a synergistic effect that&#xD;
        may improve patient survival. This study aims to explore the efficacy and safety of PD-1&#xD;
        inhibitor combined with cetuximab in neoadjuvant therapy for locally advanced HNSCC.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 20, 2023</start_date>
    <completion_date type="Anticipated">December 20, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 20, 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>Pathological Complete Response (pCR) Rate evaluated by investigators</measure>
      <time_frame>up to 13 weeks after neoadjuvant</time_frame>
      <description>pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected tumour and lymph nodes following completion of neoadjuvant therapy.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>2 years Event-free survival (EFS) Rate evaluated by investigators</measure>
      <time_frame>EFS Up to 3 years</time_frame>
      <description>Event Free Survival (EFS): EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. The 2y-EFS rate is defined as the probability of event-free survival for a patient at a given point in time (2 years).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of AEs/SAEs</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Overall incidence of adverse events (AEs); incidence of grade 3 and above AEs; incidence of serious adverse events (SAEs).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR) evaluated by investigators</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>The ORR was defined as proportion of patients whose tumor volume was reduced to 30% and sustained for more than 4 weeks as assessed by RECIST 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major Pathological Response (MPR) Rate evaluated by investigators</measure>
      <time_frame>up to 13 weeks after neoadjuvant</time_frame>
      <description>MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes in neoadjuvant therapy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>2 years Disease-free survival (DFS) Rate evaluated by investigators</measure>
      <time_frame>DFS Up to 3 years</time_frame>
      <description>DFS is defined as the time from postoperation until radiographic disease progression, local or distant recurrence, or death due to any cause. The 2y-DFS rate is defined as the probability of disease-free survival for a patient at a given point in time (2 years).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Organ Retention Rate</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Organ retention rate is defined as the proportion of patients whose tumor avoids radical surgery.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Exploratory analysis of the tumor microenvironment related with the outcome</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Exploratory analysis of the tumor microenvironment related to the outcome(including the number, function and metabolism of immune cells in tumor microenvironment).</description>
    </other_outcome>
    <other_outcome>
      <measure>Exploratory analysis of potential biomakers related with the outcome</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Exploratory analysis of potential biomarkers related to the outcome (including PD-L1 expression in tissue specimen, tumor mutation burden (TMB), whole exome sequencing (WES) ,Single-cell RNA-sequencing (scRNA-seq) and Spatial transcriptomics (ST)).</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">33</enrollment>
    <condition>Head and Neck Squamous Cell Carcinoma</condition>
    <condition>Neoadjuvant Therapy</condition>
    <arm_group>
      <arm_group_label>Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Participants receive totally 3 cycles of neoadjuvant therapy (Toripalimab+cetuximab), then radical treatment(surgery). After surgery, Participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation. Then, participants receive consolidation therapy of Toripalimab.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>3cycles (Toripalimab + cetuximab)</intervention_name>
      <description>Toripalimab by intravenous (IV) infusion every 3 weeks (Q3W), 3 preoperative and 17 consolidated doses.&#xD;
  The preoperative starting dose of cetuximab is 400 mg/m^2 by IV infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 9.</description>
      <arm_group_label>Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Surgery</intervention_name>
      <description>After neoadjuvant therapy, patients would accept surgery within 11-13 weeks.</description>
      <arm_group_label>Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Radiotherapy or chemoradiotherapy</intervention_name>
      <description>Adjuvant radiotherapy was given 4 weeks after surgery. Patients with positive intraoperative pathological margins/extra lymph node envelope invasion are treated with an additional cisplatin synchronous chemotherapy.</description>
      <arm_group_label>Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  The age at the time of enrollment is more than 18 years old and less than 70 years&#xD;
               old, both male and female.&#xD;
  &#xD;
            -  Histologically diagnosed as squamous cell carcinoma of the mouth, oropharynx,&#xD;
               hypopharynx or larynx; preoperative evaluation can be surgically resected.&#xD;
  &#xD;
            -  Have the following high-risk recurrence conditions as defined in the 8th edition of&#xD;
               the American Joint Committee on Cancer [AJCC] Guidelines: a)HPV-negative disease,&#xD;
               stage III, IVa, according to the head and Neck Tumor/lymph node/metastasis (TNM)&#xD;
               guidelines; b)non-oropharyngeal HPV-positive disease, stages III, IVa, IVb, according&#xD;
               to head and neck TNM guidelines.&#xD;
  &#xD;
            -  No previous treatment for HNSCC.&#xD;
  &#xD;
            -  Have at least one evaluable target lesion according to RECIST version 1.1 criteria.&#xD;
  &#xD;
            -  The Eastern Cancer Cooperation Organization (ECOG) physical fitness score was 0 or 1.&#xD;
  &#xD;
            -  Major organs have normal function, the following criteria are met:&#xD;
  &#xD;
            -  The standard of blood routine examination（(not transfused or receiving component blood&#xD;
               within 14 days prior to testing)：hemoglobin (HB) ≥ 9g/dL；absolute neutrophil count&#xD;
               (ANC) ≥1.5×10^9/L, platelets (PLT) ≥100×10^9/L.&#xD;
  &#xD;
            -  Biochemical examination: serum total bilirubin (TBIL) &lt;1.5 times the upper limit of&#xD;
               normal value(ULN); aspartate aminotransferase (AST) and alanine aminotransferase&#xD;
               (ALT)&lt;2.5 ULN; serum creatinine≤ULN and endogenous creatinine clearance&gt;50 mL/min&#xD;
               (Cockcroft-Gault formula) Gault formula).&#xD;
  &#xD;
            -  Signed written informed consent.&#xD;
  &#xD;
            -  Adhere to the research protocol judged by the investigator.&#xD;
  &#xD;
            -  female subjects of reproductive potential must have a negative serum pregnancy test&#xD;
               prior to the first dose of the trial drug.&#xD;
  &#xD;
            -  The male fertile patients and female fertile patients with pregnancy risk must consent&#xD;
               to the use of 2 contraceptive methods (at least one of which is considered highly&#xD;
               effective) throughout the study period.&#xD;
  &#xD;
            -  Patients who are willing and able to follow visit schedules, treatment plans,&#xD;
               laboratory tests, and other research procedures.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  prior treatment with EGFR/PD-1/PD-L1/PD-L2/CD137/CTLA-4 antibodies(including&#xD;
               ipilimumab) or activating or inhibitory agents targeting T-cell receptors.&#xD;
  &#xD;
            -  Major surgery within 4 weeks before enrollment.&#xD;
  &#xD;
            -  Proven allergic to EGFR monoclonal antibody, PD-1 antibody or its excipients.&#xD;
  &#xD;
            -  Any active autoimmune disease or history of autoimmune disease (e.g., the following:&#xD;
               interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis,&#xD;
               myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after&#xD;
               effective hormone replacement therapy), etc; patients with vitiligo or asthma in&#xD;
               complete remission in childhood may be included, adults patients with asthma who do&#xD;
               not need any intervention and require medical intervention with bronchodilators may be&#xD;
               included) .&#xD;
  &#xD;
            -  Previous or co-existing malignancies (except those that have been cured and have&#xD;
               survived cancer-free for more than 5 years, such as basal cell carcinoma of the skin,&#xD;
               carcinoma in situ of the cervix, and papillary carcinoma of the thyroid).&#xD;
  &#xD;
            -  Failure to control cardiac clinical symptoms or disease, e.g., the following: a)&#xD;
               patients with NYHAII or above heart failure, b) unstable angina pectoris c) patients&#xD;
               with myocardial infarction within 1 year, d) patients with clinically significant&#xD;
               supraventricular or ventricular arrhythmias requiring clinical intervention.&#xD;
  &#xD;
            -  Subjects requiring systemic treatment with corticosteroids (&gt; 10mg/ day prednisone&#xD;
               efficacy dose) or other immunosuppressants within 14 days prior to administration of&#xD;
               the study drug were allowed to use inhaled or topical steroids and adrenal hormone&#xD;
               replacement at a dose&gt;10mg/day prednisone efficacy dose in the absence of active&#xD;
               autoimmune disease.&#xD;
  &#xD;
            -  Have active infections that require treatment.&#xD;
  &#xD;
            -  Have a congenital or acquired immune deficiency (such as HIV infection), active&#xD;
               hepatitis B (HBV-DNA≥10^3 copy number/ml), or hepatitis C (hepatitis C antibody&#xD;
               positive and HCV-RNA above the lower detection limit of analytical methods).&#xD;
  &#xD;
            -  The patient has received other treatment before.&#xD;
  &#xD;
            -  Had received live vaccine within 4 weeks prior to starting study treatment.&#xD;
  &#xD;
            -  A known history of psychotropic substance abuse, alcohol or drug use.&#xD;
  &#xD;
            -  Pregnant or lactating women.&#xD;
  &#xD;
            -  In the investigator's judgment, the subjects had other factors that might have led to&#xD;
               their forced discontinuation of the study, such as other serious medical conditions&#xD;
               (including mental illness) requiring concomitant treatment, serious abnormalities in&#xD;
               laboratory test values, or family or social factors that might have affected the&#xD;
               safety of the subjects or the circumstances of the trial data collection.&#xD;
  &#xD;
            -  HNSCC Patients with T1/T2 or N0/N1.&#xD;
  &#xD;
            -  oral cancer, larynx cancer, hypopharyngeal cancer withT4b or N3 and P16-oropharyngeal&#xD;
               cancer.&#xD;
  &#xD;
            -  Have active pulmonary tuberculosis.&#xD;
  &#xD;
            -  Serious infections (including, but not limited to, hospitalization for complications&#xD;
               of infection, bacteremia, or severe pneumonia) that occurred within 4 weeks prior to&#xD;
               initiation of study treatment.&#xD;
  &#xD;
            -  Had received systemic immunostimulatory drugs (including but not limited to interferon&#xD;
               or interleukin-2 [IL-2]) within 4 weeks prior to initiation of study therapy or&#xD;
               remained within 5 drug half-lives (choice the longer of the two).&#xD;
  &#xD;
            -  Patients with recurrent peptic ulcers (e.g., gastric ulcers, duodenal ulcers), who&#xD;
               have a history of peptic ulcer complications such as perforation, bleeding,&#xD;
               obstruction, etc., or who have been assessed by clinicians as having a higher risk of&#xD;
               complications.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Union Hospital, Tongji Medical College, Huazhong University of Science and Technology</name>
        <address>
          <city>Wuhan</city>
          <state>Hebei</state>
          <zip>430000</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Kunyu Yang, Doctor</last_name>
        <phone>+86-13995595360</phone>
        <email>yangkunyu@hust.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 6, 2023</last_update_submitted>
    <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</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</mesh_term>
      <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>Cetuximab</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05993858
  org study id: UHCT230527
  nct id: NCT05993858
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-center, single-arm, phase II clinical study to evaluate the efficacy and
        safety of PD-1 inhibitor combined with cetuximab in neoadjuvant therapy for locally advanced
        HNSCC.
  At present, the standard treatment for patients with operable locally advanced head and neck
        squamous cell carcinoma (HNSCC) is adjuvant radiotherapy with or without platinum-based
        synchronous chemotherapy after operation. However, the risk of recurrence, metastasis and
        death remains high in this population with this intense combination treatment regimen. Both
        EGFR monoclonal antibody and PD-1 inhibitors have proven the effect in advanced HNSCC. At the
        same time, cetuximab and PD-1 inhibitors have been reported to have a synergistic effect that
        may improve patient survival. This study aims to explore the efficacy and safety of PD-1
        inhibitor combined with cetuximab in neoadjuvant therapy for locally advanced HNSCC.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Pathological Complete Response (pCR) Rate evaluated by investigators
  time frame: up to 13 weeks after neoadjuvant
  description: pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected tumour and lymph nodes following completion of neoadjuvant therapy.
  measure: 2 years Event-free survival (EFS) Rate evaluated by investigators
  time frame: EFS Up to 3 years
  description: Event Free Survival (EFS): EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. The 2y-EFS rate is defined as the probability of event-free survival for a patient at a given point in time (2 years).
  measure: Incidence of AEs/SAEs
  time frame: Up to 3 years
  description: Overall incidence of adverse events (AEs); incidence of grade 3 and above AEs; incidence of serious adverse events (SAEs).
  measure: Objective Response Rate (ORR) evaluated by investigators
  time frame: Up to 3 years
  description: The ORR was defined as proportion of patients whose tumor volume was reduced to 30% and sustained for more than 4 weeks as assessed by RECIST 1.1.
  measure: Major Pathological Response (MPR) Rate evaluated by investigators
  time frame: up to 13 weeks after neoadjuvant
  description: MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes in neoadjuvant therapy.
  measure: 2 years Disease-free survival (DFS) Rate evaluated by investigators
  time frame: DFS Up to 3 years
  description: DFS is defined as the time from postoperation until radiographic disease progression, local or distant recurrence, or death due to any cause. The 2y-DFS rate is defined as the probability of disease-free survival for a patient at a given point in time (2 years).
  measure: Organ Retention Rate
  time frame: Up to 3 years
  description: Organ retention rate is defined as the proportion of patients whose tumor avoids radical surgery.
  measure: Exploratory analysis of the tumor microenvironment related with the outcome
  time frame: Up to 3 years
  description: Exploratory analysis of the tumor microenvironment related to the outcome(including the number, function and metabolism of immune cells in tumor microenvironment).
  measure: Exploratory analysis of potential biomakers related with the outcome
  time frame: Up to 3 years
  description: Exploratory analysis of potential biomarkers related to the outcome (including PD-L1 expression in tissue specimen, tumor mutation burden (TMB), whole exome sequencing (WES) ,Single-cell RNA-sequencing (scRNA-seq) and Spatial transcriptomics (ST)).
  arm group label: Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy
  arm group type: Other
  description: Participants receive totally 3 cycles of neoadjuvant therapy (Toripalimab+cetuximab), then radical treatment(surgery). After surgery, Participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation. Then, participants receive consolidation therapy of Toripalimab.
  intervention type: Drug
  intervention name: 3cycles (Toripalimab + cetuximab)
  description: Toripalimab by intravenous (IV) infusion every 3 weeks (Q3W), 3 preoperative and 17 consolidated doses.
  The preoperative starting dose of cetuximab is 400 mg/m^2 by IV infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 9.
  arm group label: Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy
  intervention type: Procedure
  intervention name: Surgery
  description: After neoadjuvant therapy, patients would accept surgery within 11-13 weeks.
  arm group label: Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy
  intervention type: Radiation
  intervention name: Radiotherapy or chemoradiotherapy
  description: Adjuvant radiotherapy was given 4 weeks after surgery. Patients with positive intraoperative pathological margins/extra lymph node envelope invasion are treated with an additional cisplatin synchronous chemotherapy.
  arm group label: Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Squamous Cell
  mesh term: Squamous Cell Carcinoma of Head and Neck
  mesh term: Cetuximab