<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/NCT04437212</url>
  </required_header>
  <id_info>
    <org_study_id>Renji-KY2019-174</org_study_id>
    <nct_id>NCT04437212</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Locally Advanced Esophageal Cancer</brief_title>
  <official_title>A Phase II Prospective, Open-label Clinical Trial of Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Patients With Locally Advanced Esophageal Squamous Cell Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RenJi Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment&#xD;
      option for locally advanced esophageal squamous cell cancer (ESCC). However, only 20% to 40%&#xD;
      of patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with&#xD;
      favorable prognosis and about 10% of patients have disease progression after&#xD;
      chemoradiotherapy. How to improve the the efficacy of neoadjuvant therapy is an important&#xD;
      clinical problem to be solved.&#xD;
&#xD;
      Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in&#xD;
      advanced EC especially in ESCC. In Keynote181 study, for patients with metastatic esophageal&#xD;
      squamous cell carcinoma, regardless of PD-L1 expression, pembrolizumab significantly improved&#xD;
      overall survival compared with chemotherapy. However, the efficacy and safety of&#xD;
      immunotherapy therapy in surgery-based multidisciplinary treatment of local advanced&#xD;
      esophageal cancer still need a lot of clinical studies to further confirm.&#xD;
&#xD;
      The aim of this study was to evaluate the efficacy and safety of the neoadjuvant&#xD;
      chemoradiotherapy combined with perioperative toripalimab in patients with locally advanced&#xD;
      esophageal squamous cell cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>Major Pathological Response Rate (MPR)</measure>
    <time_frame>From date of surgery to 14 days later</time_frame>
    <description>No more than 10% of tumor cells were found in neoadjuvant surgical specimens.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>2-year disease-free survival</measure>
    <time_frame>From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2-year overall survival</measure>
    <time_frame>From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0</measure>
    <time_frame>60 days after the end protocol treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative complication rate</measure>
    <time_frame>From date of surgery to 30 days later</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Advanced Esophageal Squamous Cell Cancer</condition>
  <arm_group>
    <arm_group_label>Toripalimab Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive radiation therapy scheme: 41.4Gy in 23 fractions over 5 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 45mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22,29 and 2 cycles of toripalimab 240 mg every 3 weeks after chemoradiotherapy. Esophagectomy is performed 6-8 weeks after CRT completion and after operation patients received 4 cycles of toripalimab 240 mg every 3 weeks for adjuvant treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>Patients received toripalimab 240mg every 3 weeks 1-7 days after neoadjuvant chemoradiotherapy for 2 cycles before operation and 28-42 days after operation for 4 cycles.</description>
    <arm_group_label>Toripalimab Group</arm_group_label>
    <other_name>JS-001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18 to 75 years old of either gender&#xD;
&#xD;
          -  Patients with histopathological confirmed resectable thoracic esophageal squamous cell&#xD;
             carcinoma who are anti-tumor treatment-naive;&#xD;
&#xD;
          -  Clinical stage of T1-4aN1-2M0 or T3-4aN0M0 according to the 8th edition of the UICC&#xD;
             staging system;&#xD;
&#xD;
          -  ECOG PS score of 0-1;&#xD;
&#xD;
          -  The indexes of hematology, biochemistry and organ function meet the following&#xD;
             requirements: a. white blood cell count (WBC) ≥ 3.0×109/L；b. neutrophil count (ANC) ≥&#xD;
             1.5×109/L; c. platelets ≥ 85×109/L; d. hemoglobin ≥ 9g/dL; e. total bilirubin ≤&#xD;
             14.4µmol/L; f. ALT ≤ 75U/L; g. serum creatinine ≤ 104µmol/L and creatinine clearance&#xD;
             rate &gt;60 mL/min;&#xD;
&#xD;
          -  Women of childbearing age must undergo a pregnancy test within 7 days before enrolling&#xD;
             in the treatment, and those who are negative can be enrolled. Patients of childbearing&#xD;
             age and their sexual partners agree to use reliable methods of contraception before&#xD;
             entering the study, during the study, and at least 180 days after the end of the&#xD;
             study;&#xD;
&#xD;
          -  Ability to understand the study and sign informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with active infection within 2 weeks before the first use of the study drug&#xD;
             or need to be treated with oral or intravenous antibiotics;&#xD;
&#xD;
          -  A history of interstitial lung disease or non-infectious pneumonia;&#xD;
&#xD;
          -  Patients whose clinician judges surgery as the first choice for the best treatment;&#xD;
&#xD;
          -  A history of autoimmune diseases or abnormal immune system ;&#xD;
&#xD;
          -  Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung&#xD;
             dysfunction。&#xD;
&#xD;
          -  Patients diagnosed with any other malignant tumor within 5 years before enrollment,&#xD;
             except for malignant tumors with low risk of recurrence and risk of death, such as&#xD;
             fully treated basal cell or squamous cell skin and carcinoma in situ of the cervix;&#xD;
&#xD;
          -  Known or suspected allergy or hypersensitivity to monoclonal antibodies, any&#xD;
             ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;&#xD;
&#xD;
          -  A history of immunodeficiency，including a positive HIV test result or other acquired&#xD;
             or congenital immunodeficiency diseases, a history of organ transplantation or&#xD;
             allogeneic bone marrow transplantation;&#xD;
&#xD;
          -  Women during pregnancy or lactation;&#xD;
&#xD;
          -  Other situations not suitable for enrollment.&#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>Xiumei Ma, doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>RenJi Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiumei Ma, doctor</last_name>
    <phone>86-21-68683624</phone>
    <email>sallyma@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Renji Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiumei Ma, doctor</last_name>
      <phone>86-21-68383624</phone>
      <email>sallyma@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Xiumei Ma, doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>June 24, 2020</last_update_submitted>
  <last_update_submitted_qc>June 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2020</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>Neoplasms, Squamous Cell</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</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/NCT04437212
org study id: Renji-KY2019-174
nct id: NCT04437212
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment
      option for locally advanced esophageal squamous cell cancer (ESCC). However, only 20% to 40%
      of patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with
      favorable prognosis and about 10% of patients have disease progression after
      chemoradiotherapy. How to improve the the efficacy of neoadjuvant therapy is an important
      clinical problem to be solved.

      Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in
      advanced EC especially in ESCC. In Keynote181 study, for patients with metastatic esophageal
      squamous cell carcinoma, regardless of PD-L1 expression, pembrolizumab significantly improved
      overall survival compared with chemotherapy. However, the efficacy and safety of
      immunotherapy therapy in surgery-based multidisciplinary treatment of local advanced
      esophageal cancer still need a lot of clinical studies to further confirm.

      The aim of this study was to evaluate the efficacy and safety of the neoadjuvant
      chemoradiotherapy combined with perioperative toripalimab in patients with locally advanced
      esophageal squamous cell cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Major Pathological Response Rate (MPR)
time frame: From date of surgery to 14 days later
description: No more than 10% of tumor cells were found in neoadjuvant surgical specimens.
measure: 2-year disease-free survival
time frame: From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
measure: 2-year overall survival
time frame: From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months
measure: Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
time frame: 60 days after the end protocol treatment
measure: Perioperative complication rate
time frame: From date of surgery to 30 days later
arm group label: Toripalimab Group
arm group type: Experimental
description: All patients will receive radiation therapy scheme: 41.4Gy in 23 fractions over 5 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 45mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22,29 and 2 cycles of toripalimab 240 mg every 3 weeks after chemoradiotherapy. Esophagectomy is performed 6-8 weeks after CRT completion and after operation patients received 4 cycles of toripalimab 240 mg every 3 weeks for adjuvant treatment.
intervention type: Drug
intervention name: Toripalimab
description: Patients received toripalimab 240mg every 3 weeks 1-7 days after neoadjuvant chemoradiotherapy for 2 cycles before operation and 28-42 days after operation for 4 cycles.
arm group label: Toripalimab Group
other name: JS-001
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Xiumei Ma, doctor
role: Principal Investigator
affiliation: RenJi Hospital
last name: Xiumei Ma, doctor
phone: 86-21-68683624
email: sallyma@hotmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms, Squamous Cell
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma