<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/NCT03792347</url>
  </required_header>
  <id_info>
    <org_study_id>RuijinH-nit</org_study_id>
    <nct_id>NCT03792347</nct_id>
  </id_info>
  <brief_title>Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus</brief_title>
  <acronym>PALACE</acronym>
  <official_title>A Phase Ib Study of Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hecheng Li M.D., Ph.D</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ruijin Hospital</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 study will evaluate the safety and feasibility of preoperative immune checkpoint therapy&#xD;
      with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell&#xD;
      carcinoma. And this study will provide valuable information for further clinical trials of&#xD;
      preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Esophageal cancer ranks the eighth most common cancer (the fifth most common cancer in&#xD;
      China), while ESCC is the most common subtype in Asia (more than 90 % in china). Radical&#xD;
      resection is thought to be the mainstay of esophageal cancer treatment and preoperative CRT&#xD;
      is well applied in treating locally advanced esophageal cancer. In a multicohort, phase IB&#xD;
      study, pembrolizumab was used in 23 unresectable esophageal cancer patients. In this clinical&#xD;
      trial, the incidence of grade 3 treatment-related adverse events was 39 % without the&#xD;
      appearance of grade 4 and higher-grade adverse event, while the overall response rate reached&#xD;
      30 %. The safety of immune checkpoint therapy for unresected esophageal cancers using&#xD;
      nivolumab, a different PD-1 monoclonal antibody, has also been confirmed by high quality&#xD;
      clinical trials.&#xD;
&#xD;
      This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy&#xD;
      using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced&#xD;
      esophageal squamous cell carcinoma. And this study will provide valuable information for&#xD;
      further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in&#xD;
      esophageal cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Anticipated">June 17, 2020</completion_date>
  <primary_completion_date type="Actual">March 17, 2020</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>Single Group Assignment</intervention_model>
    <intervention_model_description>Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 1 and 22. Surgery will be performed within 6 weeks after completion of preoperative therapy described above</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety(The rates of grade 3 and higher-grade treatment-related adverse events)</measure>
    <time_frame>From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose</time_frame>
    <description>Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility (The rates of patients who finished pembrolizumab with chemoradiotherapy and receive surgery within 6 weeks after preoperative therapies.)</measure>
    <time_frame>From date of treatment allocation until surgery or definitive chemoradiotherapy was applied,whichever came first, assessed up to 5 months</time_frame>
    <description>Feasibility was defined as completion of surgery within 6 weeks after preoperative therapies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic complete response</measure>
    <time_frame>From date of treatment allocation and during treatment period up to 1 year</time_frame>
    <description>Pathologic complete response was defined as pT0N0M0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic response</measure>
    <time_frame>From date of treatment allocation and during treatment period up to 3 months</time_frame>
    <description>To assess radiographic response to neoadjuvant pembrolizumab with concurrent chemoradiotherapy using RECIST 1.1.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1:preoperative pembrolizumab with chemoradiotherapy group Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 15 and 29. Surgery will be performed within 6 weeks after completion of preoperative therapy described above.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Arm1：Pre-operative Pembrolizumab+chemoradiotherapy</description>
    <arm_group_label>Arm 1</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A patient will be eligible for inclusion in this study only if ALL of the following&#xD;
             criteria apply:&#xD;
&#xD;
               1. Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell&#xD;
                  carcinoma&#xD;
&#xD;
               2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1&#xD;
&#xD;
               3. Patients approve and sign the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Patients with active autoimmune disease or history of autoimmune disease 2.&#xD;
             Patients who have a condition requiring systemic treatment with either corticosteroids&#xD;
             or other immunosuppressive medications 3. Subjects with a history of symptomatic&#xD;
             interstitial lung disease 4. History of allergy to study drug components 5. Women must&#xD;
             not be pregnant or breast-feeding 6. Men with female partners (WOCBP) that are not&#xD;
             willing to use contraception 7. Patient has received prior chemotherapy, radiotherapy,&#xD;
             target therapy and immune therapy for this malignancy or for any other past malignancy&#xD;
             8. Underlying medical conditions that, in the Investigator's opinion, will make the&#xD;
             administration of study drug hazardous or obscure the interpretation of toxicity or&#xD;
             adverse events&#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>Hecheng Li, MD PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ruijin Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ruijin Hospital, Shanghai JiaoTong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>December 28, 2018</study_first_submitted>
  <study_first_submitted_qc>January 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>May 31, 2020</last_update_submitted>
  <last_update_submitted_qc>May 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ruijin Hospital</investigator_affiliation>
    <investigator_full_name>Hecheng Li M.D., Ph.D</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>esophageal squamous cell carcinoma</keyword>
  <keyword>neoadjuvant chemoradiotherapy</keyword>
  <keyword>pembrolizumab</keyword>
  <keyword>immune therapy</keyword>
  <keyword>checkpoint inhibitor</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>Esophageal Squamous Cell Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 10, 2020</submitted>
    <returned>August 25, 2020</returned>
    <submitted>November 29, 2020</submitted>
    <returned>December 23, 2020</returned>
  </pending_results>
  <!-- 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/NCT03792347
org study id: RuijinH-nit
nct id: NCT03792347
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy
      with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell
      carcinoma. And this study will provide valuable information for further clinical trials of
      preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer
      treatment.
Esophageal cancer ranks the eighth most common cancer (the fifth most common cancer in
      China), while ESCC is the most common subtype in Asia (more than 90 % in china). Radical
      resection is thought to be the mainstay of esophageal cancer treatment and preoperative CRT
      is well applied in treating locally advanced esophageal cancer. In a multicohort, phase IB
      study, pembrolizumab was used in 23 unresectable esophageal cancer patients. In this clinical
      trial, the incidence of grade 3 treatment-related adverse events was 39 % without the
      appearance of grade 4 and higher-grade adverse event, while the overall response rate reached
      30 %. The safety of immune checkpoint therapy for unresected esophageal cancers using
      nivolumab, a different PD-1 monoclonal antibody, has also been confirmed by high quality
      clinical trials.

      This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy
      using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced
      esophageal squamous cell carcinoma. And this study will provide valuable information for
      further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in
      esophageal cancer.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 1 and 22. Surgery will be performed within 6 weeks after completion of preoperative therapy described above
primary purpose: Treatment
masking: None (Open Label)
measure: Safety(The rates of grade 3 and higher-grade treatment-related adverse events)
time frame: From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose
description: Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported
measure: Feasibility (The rates of patients who finished pembrolizumab with chemoradiotherapy and receive surgery within 6 weeks after preoperative therapies.)
time frame: From date of treatment allocation until surgery or definitive chemoradiotherapy was applied,whichever came first, assessed up to 5 months
description: Feasibility was defined as completion of surgery within 6 weeks after preoperative therapies.
measure: Pathologic complete response
time frame: From date of treatment allocation and during treatment period up to 1 year
description: Pathologic complete response was defined as pT0N0M0
measure: Radiographic response
time frame: From date of treatment allocation and during treatment period up to 3 months
description: To assess radiographic response to neoadjuvant pembrolizumab with concurrent chemoradiotherapy using RECIST 1.1.
arm group label: Arm 1
arm group type: Experimental
description: Arm 1:preoperative pembrolizumab with chemoradiotherapy group Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 15 and 29. Surgery will be performed within 6 weeks after completion of preoperative therapy described above.
intervention type: Drug
intervention name: Pembrolizumab
description: Arm1：Pre-operative Pembrolizumab+chemoradiotherapy
arm group label: Arm 1
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hecheng Li, MD PHD
role: Principal Investigator
affiliation: Ruijin Hospital
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Ruijin Hospital
investigator full name: Hecheng Li M.D., Ph.D
investigator title: Professor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Pembrolizumab
sharing ipd: No
submitted: August 10, 2020
returned: August 25, 2020
submitted: November 29, 2020
returned: December 23, 2020