<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/NCT04473716</url>
  </required_header>
  <id_info>
    <org_study_id>Illuminate trial</org_study_id>
    <nct_id>NCT04473716</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients</brief_title>
  <official_title>Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients: A Single-arm Phase I Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Jiao Tong University School of Medicine</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>
      The aim of this study is to use the combination of immune checkpoint inhibitor of&#xD;
      Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy to treat the patients&#xD;
      with locally advanced OSCC, followed with radical surgery and post-operative&#xD;
      radiotherapy/chemoradiotherapy, the major pathological response and safety will be evaluated&#xD;
      as the primary surrogate endpoints, the 2-year survival rate and local recurrence rate will&#xD;
      be the second endpoints.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with locally advanced oral squamous cell carcinoma (OSCC), comprehensive&#xD;
      treatment is recommended, including surgery, radiotherapy, chemotherapy and others.&#xD;
      Pre-operative neoadjuvant therapy can reduce tumor burden, increase organ preservation rate,&#xD;
      and reduce distant metastasis rate. Pre-operative neoadjuvant therapy with paclitaxcel and&#xD;
      cisplatin (TP) has been used as one of recommended protocols in patients with locally&#xD;
      advanced head and neck squamous cell caricnoma, including OSCC. Anti-PD1/PD-L1&#xD;
      immunotherapies have achieved exciting clinical outcomes in several malignancies, such as&#xD;
      lung cancer, breast cancer, and so on. Recently, pre-operative neoadjuvant therapy with&#xD;
      combination of immunotherapy and chemotherapy agents has been used with good pathological&#xD;
      response, which might transfer to good clinical prognosis in patients with malignancies.&#xD;
      However, pre-operative neoadjuvant therapy with combination of anti-PD1 and TP in OSCC&#xD;
      patients has not been reported. The innovation of this study is the combination of immune&#xD;
      checkpoint inhibitor of Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy&#xD;
      to treat the patients with locally advanced OSCC, followed with radical surgery and&#xD;
      post-operative radiotherapy/chemoradiotherapy, the major pathological response and safety&#xD;
      will be evaluated as the primary surrogate endpoints, the 2-year survival rate and local&#xD;
      recurrence rate will be the second endpoints.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 30, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Actual">April 12, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Major pathological response</measure>
    <time_frame>One year</time_frame>
    <description>Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>2-year overall survival</measure>
    <time_frame>Two years</time_frame>
    <description>The overall survival time refers to the time from initiating inductive therapy to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2-year tumor recurrence rate</measure>
    <time_frame>Two years</time_frame>
    <description>The tumor recurrence rate is calculated using the number of patients with tumor recurrence divided by the total number of patients.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Oral Cancer</condition>
  <condition>Induction Chemotherapy</condition>
  <condition>Programmed Cell Death 1 Inhibitor</condition>
  <condition>Inductive Therapy</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-operative neoadjuvant therapy will be used with the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of paclitaxcel and cisplatin in patients with locally advanced OSCC. After inductive therapy, the patients will receive radical surgery and post-operative radiotherapy/chemoradiotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>Neoadjuvant therapy with Toripalimab of 240mg, iv, qd, on day 1, 22</description>
    <arm_group_label>Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin</arm_group_label>
    <other_name>Toripalimab for Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxcel</intervention_name>
    <description>Neoadjuvant therapy with Paclitaxcel of 260mg/m2, iv, qd, on day 1, 22</description>
    <arm_group_label>Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin</arm_group_label>
    <other_name>Paclitaxel for Injection (Albumin Bound)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Neoadjuvant therapy with Cisplatin of 75mg/m2, iv, qd, on day 1, 22</description>
    <arm_group_label>Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin</arm_group_label>
    <other_name>Cisplatin for Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radical surgery</intervention_name>
    <description>Radical surgery will be performed on the 43th-48th after initiation of inductive therapy.</description>
    <arm_group_label>Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Post-operative radiotherapy/chemoradiotherapy</intervention_name>
    <description>Post-operative radiotherapy/chemoradiotherapy will be performed within 1.5 months after radical surgery, depending on the post-operative pathological diagnosis.</description>
    <arm_group_label>Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern cooperative oncology group performance status (ECOG PS) score: 0-1 points&#xD;
&#xD;
          -  Pathological diagnosis of oral squamous cell carcinoma (including tongue, gums,&#xD;
             cheeks, mouth floor, hard palate, posterior molar region)&#xD;
&#xD;
          -  Clinical stage of III/IVA (AJCC 2018)&#xD;
&#xD;
          -  Blood routine: white blood cells &gt; 3,000/mm3, hemoglobin &gt; 8g/L, platelets &gt;&#xD;
             80,000/mm3&#xD;
&#xD;
          -  Liver function: Alanine Transaminase/Aspartate Transaminase &lt;2.5 times the upper limit&#xD;
             of normal, bilirubin &lt;1.5 times the upper limit of normal&#xD;
&#xD;
          -  Renal function: serum creatinine &lt;1.5 times the upper limit of normal&#xD;
&#xD;
          -  Sign the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  There are still unresolved toxic reactions above CTCAE level 2 caused by previous&#xD;
             anti-cancer treatment&#xD;
&#xD;
          -  Grade 3-4 allergic reactions to Toripalimab, paclitaxcel or cisplatin&#xD;
&#xD;
          -  Active severe clinical infection (&gt; CTCAE 5.0 version 2 infection)&#xD;
&#xD;
          -  Difficult to control hypertension or cardiovascular disease with clinical significance&#xD;
             (such as activity)-such as cerebrovascular accident (&lt; 6 months before treatment),&#xD;
             myocardial infarction (&lt; 6 months before treatment), unstable angina, New York&#xD;
             Cardiology Society (NYHA Appendix 5) congestive heart failure grade II or above, or&#xD;
             severe arrhythmia that cannot be controlled with drugs or has potential impact on&#xD;
             experimental treatment&#xD;
&#xD;
          -  Chronic diseases requiring immunotherapy or hormone therapy&#xD;
&#xD;
          -  Women during pregnancy or lactation&#xD;
&#xD;
          -  Participated in other clinical studies within 30 days before enrollment&#xD;
&#xD;
          -  Other circumstances that the investigator thinks are not suitable for participating in&#xD;
             the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lai-ping Zhong, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>October 4, 2022</last_update_submitted>
  <last_update_submitted_qc>October 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University</investigator_affiliation>
    <investigator_full_name>Lai-ping Zhong</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Mouth Neoplasms</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>Paclitaxel</mesh_term>
    <mesh_term>Cisplatin</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/NCT04473716
org study id: Illuminate trial
nct id: NCT04473716
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to use the combination of immune checkpoint inhibitor of
      Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy to treat the patients
      with locally advanced OSCC, followed with radical surgery and post-operative
      radiotherapy/chemoradiotherapy, the major pathological response and safety will be evaluated
      as the primary surrogate endpoints, the 2-year survival rate and local recurrence rate will
      be the second endpoints.
In patients with locally advanced oral squamous cell carcinoma (OSCC), comprehensive
      treatment is recommended, including surgery, radiotherapy, chemotherapy and others.
      Pre-operative neoadjuvant therapy can reduce tumor burden, increase organ preservation rate,
      and reduce distant metastasis rate. Pre-operative neoadjuvant therapy with paclitaxcel and
      cisplatin (TP) has been used as one of recommended protocols in patients with locally
      advanced head and neck squamous cell caricnoma, including OSCC. Anti-PD1/PD-L1
      immunotherapies have achieved exciting clinical outcomes in several malignancies, such as
      lung cancer, breast cancer, and so on. Recently, pre-operative neoadjuvant therapy with
      combination of immunotherapy and chemotherapy agents has been used with good pathological
      response, which might transfer to good clinical prognosis in patients with malignancies.
      However, pre-operative neoadjuvant therapy with combination of anti-PD1 and TP in OSCC
      patients has not been reported. The innovation of this study is the combination of immune
      checkpoint inhibitor of Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy
      to treat the patients with locally advanced OSCC, followed with radical surgery and
      post-operative radiotherapy/chemoradiotherapy, the major pathological response and safety
      will be evaluated as the primary surrogate endpoints, the 2-year survival rate and local
      recurrence rate will be the second endpoints.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Major pathological response
time frame: One year
description: Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant therapy.
measure: 2-year overall survival
time frame: Two years
description: The overall survival time refers to the time from initiating inductive therapy to death due to any cause.
measure: 2-year tumor recurrence rate
time frame: Two years
description: The tumor recurrence rate is calculated using the number of patients with tumor recurrence divided by the total number of patients.
arm group label: Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
arm group type: Experimental
description: Pre-operative neoadjuvant therapy will be used with the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of paclitaxcel and cisplatin in patients with locally advanced OSCC. After inductive therapy, the patients will receive radical surgery and post-operative radiotherapy/chemoradiotherapy.
intervention type: Drug
intervention name: Toripalimab
description: Neoadjuvant therapy with Toripalimab of 240mg, iv, qd, on day 1, 22
arm group label: Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
other name: Toripalimab for Injection
intervention type: Drug
intervention name: Paclitaxcel
description: Neoadjuvant therapy with Paclitaxcel of 260mg/m2, iv, qd, on day 1, 22
arm group label: Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
other name: Paclitaxel for Injection (Albumin Bound)
intervention type: Drug
intervention name: Cisplatin
description: Neoadjuvant therapy with Cisplatin of 75mg/m2, iv, qd, on day 1, 22
arm group label: Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
other name: Cisplatin for Injection
intervention type: Procedure
intervention name: Radical surgery
description: Radical surgery will be performed on the 43th-48th after initiation of inductive therapy.
arm group label: Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
intervention type: Radiation
intervention name: Post-operative radiotherapy/chemoradiotherapy
description: Post-operative radiotherapy/chemoradiotherapy will be performed within 1.5 months after radical surgery, depending on the post-operative pathological diagnosis.
arm group label: Neoadjuvant therapy with Toripalimab, Paclitaxcel and Cisplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Lai-ping Zhong, MD, PhD
role: Principal Investigator
affiliation: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
investigator full name: Lai-ping Zhong
investigator title: Professor
mesh term: Carcinoma, Squamous Cell
mesh term: Mouth Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Paclitaxel
mesh term: Cisplatin