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/NCT05980715</url>
    </required_header>
    <id_info>
      <org_study_id>SYSKY-2023-463-02</org_study_id>
      <nct_id>NCT05980715</nct_id>
    </id_info>
    <brief_title>PD-1 Inhibitor Therapy Versus Radiotherapy in pCR Patients With Locally Advanced HNSCC After Neoadjuvant Immunochemotherapy</brief_title>
    <acronym>HNC-SYSU-003</acronym>
    <official_title>A Randomized Controlled, Non-inferior, Phase III Study of PD-1 Inhibitor Therapy Versus Radiotherapy in pCR Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Neoadjuvant Immunochemotherapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>First People's Hospital of Foshan</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>First Affiliated Hospital, Sun Yat-Sen University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Affiliated Cancer Hospital of Shantou University Medical College</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</source>
    <oversight_info>
      <has_dmc>No</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>
        In patients with locally advanced head and neck squamous cell carcinoma undergoing standard&#xD;
        surgical treatment after neoadjuvant immunochemotherapy, can PD-1 inhibitor therapy be used&#xD;
        instead of adjuvant radiotherapy for both primary and lymph node pathology? To provide&#xD;
        further evidence-based medical evidence for the late precision treatment of HNSCC patients&#xD;
        after neoadjuvant immunochemotherapy. Avoid the side effects caused by excessive&#xD;
        radiotherapy, especially avoid the occurrence of second primary cancer, radiation&#xD;
        osteonecrosis and other diseases.&#xD;
  &#xD;
          1. Main study endpoint:&#xD;
  &#xD;
             A randomized controlled, non-inferiority, multicentre Phase III trial was conducted to&#xD;
             investigate the difference in 5-year overall survival (OS) between experimental group&#xD;
             (Group B) and control group (group A) in patients undergoing standard surgical treatment&#xD;
             after neoadjuvant immunochemotherapy for locally advanced HNSCC, with both primary and&#xD;
             lymph node pathology revealed by pCR. At the same time, adverse events and safety were&#xD;
             evaluated according to NCI-CTCAE 5.0 criteria and RTOG later radiotherapy damage&#xD;
             evaluation criteria.&#xD;
  &#xD;
             Safety indicators focused on late radiotherapy toxicity and the incidence of grade 3 and&#xD;
             4 adverse reactions in NCI-CTC AE 5.0 and RTOG. The differences in the incidence of&#xD;
             grade 3 and 4 adverse events were compared between the experimental group and the&#xD;
             control group.&#xD;
  &#xD;
          2. Secondary study endpoint:&#xD;
  &#xD;
        The differences in 2-year disease-free survival (DFS), regional relapse-free survival (RRFS),&#xD;
        distant metastasis free survival (DMFS), safety and adverse events were compared.&#xD;
  &#xD;
        Safety evaluation NCI-CTC AE 5.0 standard was used to evaluate the acute safety index of&#xD;
        radiotherapy, and RTOG late-stage damage evaluation standard was used to evaluate the&#xD;
        late-stage safety index of radiotherapy.&#xD;
  &#xD;
        4) Exploratory goals The influence of prognostic laboratory indicators, clinical risk factors&#xD;
        were analyzed. To explore the factors that influence the efficacy of radiotherapy after pCR&#xD;
        immunotherapy.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2030</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2030</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>Overall survival(OS)</measure>
      <time_frame>5 years</time_frame>
      <description>Overall survival(OS) is the time from day 1 of study treatment(the time randomized) until death from any cause.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>The percentage of Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG</measure>
      <time_frame>5 years</time_frame>
      <description>The incidence(percentage) of late toxicity , Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Disease-free survival （DFS）</measure>
      <time_frame>2 years</time_frame>
      <description>DFS(by months) is defined as the time from treatment until the date of the first relapse (local/regional recurrence or distant metastasis) or death (from any cause) whichever comes firsts and regardless of whether the patient withdraws from treatment or receives another anti-cancer therapy prior to disease DFS is defined as the time from treatment until the date of the first relapse (local/regional recurrence or distant metastasis) or death (from any cause) whichever comes firsts and regardless of whether the patient withdraws from treatment or receives another anti-cancer therapy prior to disease relapse.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>regional recurrence-free survival (RRFS)</measure>
      <time_frame>2 years</time_frame>
      <description>The time( by months) from randomization to clinically confirmed recurrence in the lymph node drainage area. Deaths were counted in RRFS.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>distant metastasis free survival (DMFS)</measure>
      <time_frame>2 years</time_frame>
      <description>The time( by months) from randomization to clinically confirmed distant metastasis.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number and percentage of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and RTOG</measure>
      <time_frame>2 years</time_frame>
      <description>The detail number and percentage of adverse events by every systems Assessed by CTCAE v5.0 and RTOG.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">324</enrollment>
    <condition>HNSCC</condition>
    <condition>Radiotherapy</condition>
    <condition>PD-1</condition>
    <arm_group>
      <arm_group_label>Arm 1（PD-1）</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Radiotherapy free treatment: the experimental group took PD-1 inhibitor maintenance regimen.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm 2（radiotherapy）</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>conventional radiotherapy (chemoradiotherapy) regimen, and received comprehensive treatment according to the guidelines (radiotherapy or platinum-based concurrent chemoradiotherapy as stipulated in the guidelines).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>PD-1inhibitor</intervention_name>
      <description>The PD-1 monoclonal antibody was the same as the neoadjuvant therapy before surgery, and the postoperative level was maintained at Q3*6.</description>
      <arm_group_label>Arm 1（PD-1）</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>concurrent chemoradiotherapy</intervention_name>
      <description>According to the guidelines, concurrent chemoradiotherapy is required, and carboplatin (50mg/m2) plus concurrent radiotherapy or cisplatin (30mg/m2) plus concurrent radiotherapy is optional.</description>
      <arm_group_label>Arm 2（radiotherapy）</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  In this study, patients with locally advanced head and neck squamous cell carcinoma&#xD;
               (AJCC 8th) who underwent standard surgical treatment after neoadjuvant&#xD;
               immunochemotherapy and showed pCR in both primary lesions and lymph node pathology&#xD;
               were selected. Locally advanced squamous cell carcinoma of head and neck includes: i)&#xD;
               T3, N0, M0; 2) T1-T3, N1-N2, M0; 3) T4a, N0-2, M0.&#xD;
  &#xD;
            -  No history of other malignant tumors&#xD;
  &#xD;
            -  Ages 18-65&#xD;
  &#xD;
            -  Normal baseline inspection:&#xD;
  &#xD;
                 1. The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14 days&#xD;
                    without the use of granulocyte colony stimulating factor;&#xD;
  &#xD;
                 2. Platelets ≥100×109/L without blood transfusion in the past 14 days;&#xD;
  &#xD;
                 3. Hemoglobin &amp;gt without blood transfusion or use of erythropoietin within the last&#xD;
                    14 days; 9g/dL;&#xD;
  &#xD;
                 4. Total bilirubin ≤1.5× upper limit of normal value (ULN);&#xD;
  &#xD;
                 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (ALT&#xD;
                    or AST ≤5×ULN in patients with liver metastasis);&#xD;
  &#xD;
                 6. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault&#xD;
                    formula) ≥60 ml/min;&#xD;
  &#xD;
                 7. Good coagulation function, defined as International Standardized ratio (INR) or&#xD;
                    prothrombin time (PT) ≤1.5 times ULN;&#xD;
  &#xD;
                 8. Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the&#xD;
                    normal range. Subjects whose baseline TSH is outside the normal range can be&#xD;
                    enrolled if total T3 (or FT3) and FT4 are within the normal range;&#xD;
  &#xD;
                 9. The myocardial enzyme profile was within the normal range (if the researchers&#xD;
                    comprehensively judged that the simple laboratory abnormality was not clinically&#xD;
                    significant, it was also allowed to be included);&#xD;
  &#xD;
                10. For female subjects of childbearing age, a urine or serum pregnancy test should&#xD;
                    be tested negative within 3 days prior to receiving the first study drug&#xD;
                    administration (day 1 of Cycle 1). If the urine pregnancy test results cannot be&#xD;
                    confirmed negative, a blood pregnancy test is requested. Women of&#xD;
                    non-reproductive age were defined as at least one year after menopause or having&#xD;
                    undergone surgical sterilization or hysterectomy;&#xD;
  &#xD;
                11. If there is a risk of conception, all subjects (male or female) shall use&#xD;
                    contraception with an annual failure rate of less than 1% for the entire duration&#xD;
                    of treatment up to 120 days after the last study drug administration (or 180 days&#xD;
                    after the last chemotherapeutic drug administration).&#xD;
  &#xD;
               5 Sign informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1 HNSCC is not the initial diagnosis of other malignant tumors or neoadjuvant therapy.&#xD;
  &#xD;
            -  Prior to treatment An active autoimmune immune disease requiring systemic therapy&#xD;
               (e.g. the use of disease-modifying drugs, glucocorticoids, or immunosuppressants) has&#xD;
               occurred in the last 2 years. Alternative therapies (such as thyroxine, insulin, or&#xD;
               physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered&#xD;
               systemic therapy;&#xD;
  &#xD;
            -  Known allogeneic organ transplantation (except corneal transplantation) or allogeneic&#xD;
               hematopoietic stem cell transplantation;&#xD;
  &#xD;
            -  Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody&#xD;
               positive);&#xD;
  &#xD;
            -  Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number&#xD;
               detected greater than the upper limit of normal value in the laboratory of the study&#xD;
               center);&#xD;
  &#xD;
          Note: Hepatitis B subjects who meet the following criteria can also be enrolled:&#xD;
  &#xD;
          1) HBV viral load &amp;lt before initial administration; At 1000 copies /ml (200 IU/ml),&#xD;
          subjects should receive anti-HBV therapy to avoid viral reactivation throughout the study&#xD;
          treatment period 2) For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-), and HBV viral&#xD;
          load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral&#xD;
          reactivation is required&#xD;
  &#xD;
            -  Active HCV infected subjects (HCV antibody positive and HCV-RNA level above the lower&#xD;
               limit);&#xD;
  &#xD;
            -  Pregnant or lactating women;&#xD;
  &#xD;
            -  The presence of any serious or uncontrolled systemic disease, such as:&#xD;
  &#xD;
                 1. The resting electrocardiogram (ECG) presents significant and severely&#xD;
                    uncontrollable abnormalities in rhythm, conduction or morphology, such as&#xD;
                    complete left bundle branch block, Ⅱ degree or above heart block, ventricular&#xD;
                    arrhythmia or atrial fibrillation;&#xD;
  &#xD;
                 2. Unstable angina pectoris, congestive heart failure, and NYHA grade ≥ 2 chronic&#xD;
                    heart failure;&#xD;
  &#xD;
                 3. Any arterial thrombosis, embolism or ischemia, such as myocardial infarction,&#xD;
                    unstable angina pectoris, cerebrovascular accident or transient ischemic attack,&#xD;
                    occurred within 6 months before treatment;&#xD;
  &#xD;
                 4. Poor blood pressure control (systolic &gt; 140 mmHg, diastolic &gt; 90 mmHg);&#xD;
  &#xD;
                 5. A history of non-infectious pneumonia requiring glucocorticoid therapy or&#xD;
                    clinically active interstitial lung disease within 1 year prior to initial&#xD;
                    administration;&#xD;
  &#xD;
                 6. Active pulmonary tuberculosis;&#xD;
  &#xD;
                 7. There is an active or uncontrolled infection that requires systemic treatment;&#xD;
  &#xD;
                 8. Clinically active diverticulitis, abdominal abscess, gastrointestinal&#xD;
                    obstruction;&#xD;
  &#xD;
                 9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic&#xD;
                    active hepatitis;&#xD;
  &#xD;
                10. Poor diabetes control (fasting blood glucose (FBG) &gt; 10mmol/L);&#xD;
  &#xD;
                11. Urine routine indicated urine protein ≥++, and confirmed 24 hours urine protein&#xD;
                    quantity &gt; 1.0 g;&#xD;
  &#xD;
                12. Patients with mental disorders and unable to cooperate with treatment;&#xD;
  &#xD;
            -  Medical history or evidence of disease that may interfere with test results, prevent&#xD;
               subjects from fully participating in the study, abnormal values of treatment or&#xD;
               laboratory tests, or other conditions that the investigator considers unsuitable for&#xD;
               enrollment. The investigator considers other potential risks unsuitable for&#xD;
               participation in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Jinsong Li, MD</last_name>
      <phone>008618583879908</phone>
      <email>caobleat@hotmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Haotian Cao, MD</last_name>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Sun yat-sen memorial hospital</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Haotian Cao, MD</last_name>
        <phone>008618583879908</phone>
        <email>caobleat@hotmail.com</email>
      </contact>
      <contact_backup>
        <last_name>Jinsong Li, MD</last_name>
      </contact_backup>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 5, 2023</study_first_submitted>
    <study_first_submitted_qc>August 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 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 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HNSCC</keyword>
    <keyword>radiotherapy</keyword>
    <keyword>PD-1</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <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>Immune Checkpoint Inhibitors</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05980715
  org study id: SYSKY-2023-463-02
  nct id: NCT05980715
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  In patients with locally advanced head and neck squamous cell carcinoma undergoing standard
        surgical treatment after neoadjuvant immunochemotherapy, can PD-1 inhibitor therapy be used
        instead of adjuvant radiotherapy for both primary and lymph node pathology? To provide
        further evidence-based medical evidence for the late precision treatment of HNSCC patients
        after neoadjuvant immunochemotherapy. Avoid the side effects caused by excessive
        radiotherapy, especially avoid the occurrence of second primary cancer, radiation
        osteonecrosis and other diseases.
  
          1. Main study endpoint:
  
             A randomized controlled, non-inferiority, multicentre Phase III trial was conducted to
             investigate the difference in 5-year overall survival (OS) between experimental group
             (Group B) and control group (group A) in patients undergoing standard surgical treatment
             after neoadjuvant immunochemotherapy for locally advanced HNSCC, with both primary and
             lymph node pathology revealed by pCR. At the same time, adverse events and safety were
             evaluated according to NCI-CTCAE 5.0 criteria and RTOG later radiotherapy damage
             evaluation criteria.
  
             Safety indicators focused on late radiotherapy toxicity and the incidence of grade 3 and
             4 adverse reactions in NCI-CTC AE 5.0 and RTOG. The differences in the incidence of
             grade 3 and 4 adverse events were compared between the experimental group and the
             control group.
  
          2. Secondary study endpoint:
  
        The differences in 2-year disease-free survival (DFS), regional relapse-free survival (RRFS),
        distant metastasis free survival (DMFS), safety and adverse events were compared.
  
        Safety evaluation NCI-CTC AE 5.0 standard was used to evaluate the acute safety index of
        radiotherapy, and RTOG late-stage damage evaluation standard was used to evaluate the
        late-stage safety index of radiotherapy.
  
        4) Exploratory goals The influence of prognostic laboratory indicators, clinical risk factors
        were analyzed. To explore the factors that influence the efficacy of radiotherapy after pCR
        immunotherapy.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall survival(OS)
  time frame: 5 years
  description: Overall survival(OS) is the time from day 1 of study treatment(the time randomized) until death from any cause.
  measure: The percentage of Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG
  time frame: 5 years
  description: The incidence(percentage) of late toxicity , Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG.
  measure: Disease-free survival （DFS）
  time frame: 2 years
  description: DFS(by months) is defined as the time from treatment until the date of the first relapse (local/regional recurrence or distant metastasis) or death (from any cause) whichever comes firsts and regardless of whether the patient withdraws from treatment or receives another anti-cancer therapy prior to disease DFS is defined as the time from treatment until the date of the first relapse (local/regional recurrence or distant metastasis) or death (from any cause) whichever comes firsts and regardless of whether the patient withdraws from treatment or receives another anti-cancer therapy prior to disease relapse.
  measure: regional recurrence-free survival (RRFS)
  time frame: 2 years
  description: The time( by months) from randomization to clinically confirmed recurrence in the lymph node drainage area. Deaths were counted in RRFS.
  measure: distant metastasis free survival (DMFS)
  time frame: 2 years
  description: The time( by months) from randomization to clinically confirmed distant metastasis.
  measure: Number and percentage of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and RTOG
  time frame: 2 years
  description: The detail number and percentage of adverse events by every systems Assessed by CTCAE v5.0 and RTOG.
  arm group label: Arm 1（PD-1）
  arm group type: Experimental
  description: Radiotherapy free treatment: the experimental group took PD-1 inhibitor maintenance regimen.
  arm group label: Arm 2（radiotherapy）
  arm group type: Active Comparator
  description: conventional radiotherapy (chemoradiotherapy) regimen, and received comprehensive treatment according to the guidelines (radiotherapy or platinum-based concurrent chemoradiotherapy as stipulated in the guidelines).
  intervention type: Drug
  intervention name: PD-1inhibitor
  description: The PD-1 monoclonal antibody was the same as the neoadjuvant therapy before surgery, and the postoperative level was maintained at Q3*6.
  arm group label: Arm 1（PD-1）
  intervention type: Radiation
  intervention name: concurrent chemoradiotherapy
  description: According to the guidelines, concurrent chemoradiotherapy is required, and carboplatin (50mg/m2) plus concurrent radiotherapy or cisplatin (30mg/m2) plus concurrent radiotherapy is optional.
  arm group label: Arm 2（radiotherapy）
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Jinsong Li, MD
  phone: 008618583879908
  email: caobleat@hotmail.com
  last name: Haotian Cao, MD
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: China
  responsible party type: Sponsor
  mesh term: Squamous Cell Carcinoma of Head and Neck
  mesh term: Immune Checkpoint Inhibitors
  sharing ipd: No