<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/NCT04435197</url>
  </required_header>
  <id_info>
    <org_study_id>RTS-010</org_study_id>
    <nct_id>NCT04435197</nct_id>
  </id_info>
  <brief_title>Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma</brief_title>
  <acronym>PALACE-2</acronym>
  <official_title>Multicenter Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophageus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fujian Medical University Union Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Anhui Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Nanchang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>
      To investigate the safety and activity of preoperative pembrolizumab combined with&#xD;
      chemoradiotherapy for resectable esophageal squamous cell carcinoma (ESCC) ,20 patients&#xD;
      enrolled in Phase Ib PALACE-1(NCT03792347).The results showed that preoperative pembrolizumab&#xD;
      with concurrent chemoradiotherapy was safe, did not delay surgery and induced a pCR in 55.6%&#xD;
      of resected tumors. In this multicentre prospective study(PALACE-2),the investigators will&#xD;
      evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in&#xD;
      patients with locally advanced esophageal squamous cell carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy&#xD;
      followed by surgery has been recommended as the optimal therapeutic strategy.Patients who&#xD;
      achieved pathologic complete response(pCR) after receiving neoadjuvant therapy were more&#xD;
      likely to have better survival. And the pCR rates was 43.2% reported in NEOCRTEC5010 trial,&#xD;
      49% with ESCC in the CROSS trial and 33.3% in FFCD 990130.&#xD;
&#xD;
      In Phase Ib PALACE-1(NCT03792347), the investigators firstly present that preoperative&#xD;
      pembrolizumab combined with chemoradiotherapy followed by surgery is safe.All 20 patients&#xD;
      have received PPCT successfully, except 1 patient who missed the last dose of chemotherapy&#xD;
      due to leukopenia. Grade 3 and higher adverse events (AEs) were observed in 13 patients&#xD;
      (13/20, 65%), and 1 patient had a grade 5 AE. The most frequent grade 3 AE was lymphopenia&#xD;
      (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR&#xD;
      rate was 55.6% (10/18).&#xD;
&#xD;
      This study (PALACE-2) will evaluate the efficacy of preoperative pembrolizumab with&#xD;
      concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell&#xD;
      carcinoma in multicentres.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 11, 2020</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>
    <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 4-6 weeks after completion of preoperative therapy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathologic complete response</measure>
    <time_frame>1 month after resection</time_frame>
    <description>Pathologic complete response was defined as pT0N0M0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>3-year disease free survival</measure>
    <time_frame>3 years after resection</time_frame>
    <description>Percentage of Participants With 3-Year disease-Free Survival (DFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Disease free survival defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>5 years</time_frame>
    <description>OS is defined as the time from enrollment to death due to any cause</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">143</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1:&#xD;
A: Pembrolizumab 200mg(100mg if weight less than 50kg) IV on days 1 and 22 B: Carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week.&#xD;
D: Ivor-Lewis or McKeown esophagectomy&#xD;
The participants will receive preoperative A+B+C. 4-6 weeks after completion of preoperative therapy ，D will be performed if there is no contraindication.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab Injection</intervention_name>
    <description>Pre-operative Pembrolizumab+chemoradiotherapy</description>
    <arm_group_label>Arm A</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.&#xD;
&#xD;
          2. Patients who have a condition requiring systemic treatment with either corticosteroids&#xD;
             or other immunosuppressive medications.&#xD;
&#xD;
          3. Subjects with a history of symptomatic interstitial lung disease.&#xD;
&#xD;
          4. History of allergy to study drug components.&#xD;
&#xD;
          5. Women must not be pregnant or breast-feeding.&#xD;
&#xD;
          6. Men with female partners (WOCBP) that are not willing to use contraception.&#xD;
&#xD;
          7. Patient has received prior chemotherapy, radiotherapy, target therapy and immune&#xD;
             therapy for this malignancy or for any other past malignancy.&#xD;
&#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&amp;PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hecheng Li, MD,PHD</last_name>
    <phone>00862164370045</phone>
    <phone_ext>00862164370045</phone_ext>
    <email>lihecheng2000@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chengqiang Li, MD</last_name>
    <phone>00862164370045</phone>
    <email>whipple@yeah.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ruijin Hospital, Shanghai Jiao Tong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hecheng Li, MD,PHD</last_name>
      <phone>021-64370045</phone>
      <email>lihecheng2000@hotmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Chengqiang Li, MD</last_name>
      <phone>13524282905</phone>
      <email>lcq12305@rjh.com.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Hecheng Li, MD,PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Chengqiang Li, MD</last_name>
      <phone>13524282905</phone>
      <phone_ext>666112</phone_ext>
      <email>whipple@yeah.net</email>
    </contact>
    <contact_backup>
      <last_name>Yuyan Zheng, MD</last_name>
      <phone>00862164370045</phone>
      <phone_ext>666112</phone_ext>
      <email>yuyanzheng@outlook.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>April 20, 2023</last_update_submitted>
  <last_update_submitted_qc>April 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ruijin Hospital</investigator_affiliation>
    <investigator_full_name>Hecheng Li M.D., Ph.D</investigator_full_name>
    <investigator_title>Chair of thoracic department</investigator_title>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>Pathologic complete response</keyword>
  <keyword>preoperative pembrolizumab with concurrent chemoradiotherapy</keyword>
  <keyword>Disease-free Survival</keyword>
  <keyword>Median overall survival</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>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04435197
org study id: RTS-010
nct id: NCT04435197
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
To investigate the safety and activity of preoperative pembrolizumab combined with
      chemoradiotherapy for resectable esophageal squamous cell carcinoma (ESCC) ,20 patients
      enrolled in Phase Ib PALACE-1(NCT03792347).The results showed that preoperative pembrolizumab
      with concurrent chemoradiotherapy was safe, did not delay surgery and induced a pCR in 55.6%
      of resected tumors. In this multicentre prospective study(PALACE-2),the investigators will
      evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in
      patients with locally advanced esophageal squamous cell carcinoma.
For locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy
      followed by surgery has been recommended as the optimal therapeutic strategy.Patients who
      achieved pathologic complete response(pCR) after receiving neoadjuvant therapy were more
      likely to have better survival. And the pCR rates was 43.2% reported in NEOCRTEC5010 trial,
      49% with ESCC in the CROSS trial and 33.3% in FFCD 990130.

      In Phase Ib PALACE-1(NCT03792347), the investigators firstly present that preoperative
      pembrolizumab combined with chemoradiotherapy followed by surgery is safe.All 20 patients
      have received PPCT successfully, except 1 patient who missed the last dose of chemotherapy
      due to leukopenia. Grade 3 and higher adverse events (AEs) were observed in 13 patients
      (13/20, 65%), and 1 patient had a grade 5 AE. The most frequent grade 3 AE was lymphopenia
      (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR
      rate was 55.6% (10/18).

      This study (PALACE-2) will evaluate the efficacy of preoperative pembrolizumab with
      concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell
      carcinoma in multicentres.
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 4-6 weeks after completion of preoperative therapy.
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic complete response
time frame: 1 month after resection
description: Pathologic complete response was defined as pT0N0M0
measure: 3-year disease free survival
time frame: 3 years after resection
description: Percentage of Participants With 3-Year disease-Free Survival (DFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Disease free survival defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.
measure: Overall Survival (OS)
time frame: 5 years
description: OS is defined as the time from enrollment to death due to any cause
arm group label: Arm A
arm group type: Experimental
description: Arm 1:
A: Pembrolizumab 200mg(100mg if weight less than 50kg) IV on days 1 and 22 B: Carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week.
D: Ivor-Lewis or McKeown esophagectomy
The participants will receive preoperative A+B+C. 4-6 weeks after completion of preoperative therapy ，D will be performed if there is no contraindication.
intervention type: Drug
intervention name: Pembrolizumab Injection
description: Pre-operative Pembrolizumab+chemoradiotherapy
arm group label: Arm A
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 hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine
last name: Hecheng Li, MD,PHD
phone: 00862164370045
phone ext: 00862164370045
email: lihecheng2000@hotmail.com
last name: Chengqiang Li, MD
phone: 00862164370045
email: whipple@yeah.net
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Ruijin Hospital
investigator full name: Hecheng Li M.D., Ph.D
investigator title: Chair of thoracic department
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Pembrolizumab
sharing ipd: Undecided