<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/NCT04460066</url>
  </required_header>
  <id_info>
    <org_study_id>ZKAB001-LEES-2020-02</org_study_id>
    <nct_id>NCT04460066</nct_id>
  </id_info>
  <brief_title>A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma.</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Phase Ib/II Clinical Study of Anti-pd-l1 Monoclonal Antibody Injection (ZKAB001) Combined Albumin Binding Paclitaxel, Cisplatin in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lee's Pharmaceutical Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lee's Pharmaceutical Limited</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 is a randomized, double-blind, placebo-controlled Ib/Ⅱ clinical study to evaluate the&#xD;
      safety and effect of anti-PD-L1 antibody (ZKAB001) in neoadjuvant chemotherapy of esophageal&#xD;
      squamous carcinoma in combination with Alb-paclitaxel and cisplatin. The immunotherapy will&#xD;
      be given before and after the operation every three weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 18, 2020</start_date>
  <completion_date type="Anticipated">July 15, 2023</completion_date>
  <primary_completion_date type="Actual">December 6, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>major pathologic response rate</measure>
    <time_frame>Two weeks after surgery.</time_frame>
    <description>The rate of pathologic 1a and 1b after neoadjuvant chemotherapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>R0 resection rate</measure>
    <time_frame>Two weeks after surgery.</time_frame>
    <description>The R0 resection rate of esophagectomy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pathological complete response rate</measure>
    <time_frame>Two weeks after surgery.</time_frame>
    <description>The rate of pathologic 1a after neoadjuvant chemotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease free survival</measure>
    <time_frame>From the date of surgery until the date of death due to disease progression or the date of first documented disease progression whichever came first, assessed up to 24 months.</time_frame>
    <description>The 2-year disease free survival of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease free survival rate</measure>
    <time_frame>From the date of surgery until the date of death due to disease progression or the date of first documented disease progression whichever came first, assessed up to 24 months.</time_frame>
    <description>The 2-year disease free survival rate of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>event free survival</measure>
    <time_frame>From the date of randomization 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>
    <description>The 2-year event free survival of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>event free survival rate</measure>
    <time_frame>From the date of randomization 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>
    <description>The 2-year event free survival rate of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival rate</measure>
    <time_frame>From the 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>
    <description>The 2-year overall survival rate of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>From the 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>
    <description>The 2-year overall survival of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events rate</measure>
    <time_frame>From the date of randomization to 90 days after the last chemotherapy.</time_frame>
    <description>The incidence rate of treatment-related adverse events of the whole group assessed by CTCAE v5.0.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Esophageal Cancer</condition>
  <arm_group>
    <arm_group_label>PD-L1 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive 16 cycles of anti-PD-L1 antibody (5mg/kg, IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>All patients will receive 4 cycles of placebo ( IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>anti-PD-L1 antibody</intervention_name>
    <description>Patients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks.</description>
    <arm_group_label>PD-L1 group</arm_group_label>
    <other_name>ZKAB001</other_name>
    <other_name>Socazolimab Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>albumin bound paclitaxel</intervention_name>
    <description>Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .</description>
    <arm_group_label>PD-L1 group</arm_group_label>
    <arm_group_label>placebo group</arm_group_label>
    <other_name>ABRAXANE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatin</intervention_name>
    <description>Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.</description>
    <arm_group_label>PD-L1 group</arm_group_label>
    <arm_group_label>placebo group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Patients will receive 4 cycles of placebo IV on day 1 every 3 weeks.</description>
    <arm_group_label>placebo group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>radical resection of esophageal carcinoma</intervention_name>
    <description>Patients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy.</description>
    <arm_group_label>PD-L1 group</arm_group_label>
    <arm_group_label>placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key inclusion Criteria:&#xD;
&#xD;
          1. Aged 18 to 75 years old of either gender;&#xD;
&#xD;
          2. A histopathological diagnosis of esophageal squamous cell carcinoma with a clinical&#xD;
             stage of T2N+M0 or T3-4aN+/-M0 according to the 8th edition of the UICC staging&#xD;
             system;&#xD;
&#xD;
          3. ECOG score 0-1;&#xD;
&#xD;
          4. Estimated life expectancy &gt;3 months;&#xD;
&#xD;
          5. BMI ≥18.5kg/m2 or PG-SGA score A/B;&#xD;
&#xD;
          6. The function of important organs meets the following requirements:&#xD;
&#xD;
               1. white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥&#xD;
                  1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L;&#xD;
&#xD;
               2. ALT, AST and AKP ≤ 2.5×ULN;&#xD;
&#xD;
               3. serum albumin ≥ 30g/L;&#xD;
&#xD;
               4. total bilirubin ≤ 1.5×ULN;&#xD;
&#xD;
               5. serum creatinine ≤ 1.0×ULN, creatinine clearance rate ≥60 mL/min;&#xD;
&#xD;
               6. INR ≤ 1.5, PT≤ 1.5×ULN;&#xD;
&#xD;
          7. Cardiac function: ≤I, pulmonary function: FEV1 &gt;1.2L, FEV1% &gt;40%, liver function:&#xD;
             Child-Pugh 5-6;&#xD;
&#xD;
          8. Serum HCG negative in premenopausal women ;&#xD;
&#xD;
          9. Ability to understand the study and sign informed consent.&#xD;
&#xD;
        Key exclusion Criteria:&#xD;
&#xD;
          1. Cervical esophageal carcinoma;&#xD;
&#xD;
          2. Patients who have been treated previously with anti-tumor therapy (including&#xD;
             chemotherapy, radiotherapy, surgery, immunotherapy, etc.);&#xD;
&#xD;
          3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any&#xD;
             ingredients of anti-PD-L1 antibody and chemotherapeutic drugs;&#xD;
&#xD;
          4. Active autoimmune diseases;&#xD;
&#xD;
          5. A history of allogeneic stem cell transplantation and organ transplantation;&#xD;
&#xD;
          6. A history of interstitial lung disease or non-infectious pneumonia;&#xD;
&#xD;
          7. Patients who cannot tolerate chemotherapy or surgery due to severe cardiac, lung,&#xD;
             liver or kidney dysfunction, or hematopoietic disease or cachexia;&#xD;
&#xD;
          8. A history of immunodeficiency (including a positive HIV test result), or other&#xD;
             acquired or congenital immunodeficiency diseases;&#xD;
&#xD;
          9. Presence of active hepatitis B (HBV DNA ≥ 200 IU/mL or 103 copies/mL), hepatitis C&#xD;
             (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of&#xD;
             the assay);&#xD;
&#xD;
         10. A history of active pulmonary tuberculosis infection within 1 year or a history of&#xD;
             active pulmonary tuberculosis infection more than 1 year ago but without formal&#xD;
             anti-tuberculosis treatment;&#xD;
&#xD;
         11. A history of malignancies other than esophageal cancer before enrollment, excluding&#xD;
             non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;&#xD;
&#xD;
         12. Lymph node metastasis in neck, supraclavicular, abdominal cavity, retroperitoneum and&#xD;
             pelvic cavity (except paracardial and left gastric lymph nodes).&#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>SHUGENG GAO, MD</last_name>
    <role>Study Director</role>
    <affiliation>Chinese Academy of Medical Sciences and Peking Union Medical College</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chinese Academy of Medical Sciences and Peking Union Medical College</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://gco.iarc.fr/today/data/factsheets/cancers/6Oesophagus-fact-sheet.pdf.</url>
    <description>GLOBOCAN 2018: oesophagus cancer fact sheet</description>
  </link>
  <reference>
    <citation>Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. doi: 10.1056/NEJM199812313392704.</citation>
    <PMID>9869669</PMID>
  </reference>
  <reference>
    <citation>Lin CC, Hsu CH, Cheng JC, Wang HP, Lee JM, Yeh KH, Yang CH, Lin JT, Cheng AL, Lee YC. Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal cancer. Ann Oncol. 2007 Jan;18(1):93-98. doi: 10.1093/annonc/mdl339. Epub 2006 Oct 6.</citation>
    <PMID>17028244</PMID>
  </reference>
  <reference>
    <citation>Polee MB, Tilanus HW, Eskens FA, Hoekstra R, Van der Burg ME, Siersema PD, Stoter G, Van der Gaast A. Phase II study of neo-adjuvant chemotherapy with paclitaxel and cisplatin given every 2 weeks for patients with a resectable squamous cell carcinoma of the esophagus. Ann Oncol. 2003 Aug;14(8):1253-7. doi: 10.1093/annonc/mdg328.</citation>
    <PMID>12881388</PMID>
  </reference>
  <reference>
    <citation>Shapiro J, van Hagen P, Lingsma HF, Wijnhoven BP, Biermann K, ten Kate FJ, Steyerberg EW, van der Gaast A, van Lanschot JJ; CROSS Study Group. Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg. 2014 Nov;260(5):807-13; discussion 813-4. doi: 10.1097/SLA.0000000000000966.</citation>
    <PMID>25379852</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>April 28, 2022</last_update_submitted>
  <last_update_submitted_qc>April 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>esophageal cancer</keyword>
  <keyword>immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Neoplasms</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>Paclitaxel</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Antibodies</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/NCT04460066
org study id: ZKAB001-LEES-2020-02
nct id: NCT04460066
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a randomized, double-blind, placebo-controlled Ib/Ⅱ clinical study to evaluate the
      safety and effect of anti-PD-L1 antibody (ZKAB001) in neoadjuvant chemotherapy of esophageal
      squamous carcinoma in combination with Alb-paclitaxel and cisplatin. The immunotherapy will
      be given before and after the operation every three weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: major pathologic response rate
time frame: Two weeks after surgery.
description: The rate of pathologic 1a and 1b after neoadjuvant chemotherapy.
measure: R0 resection rate
time frame: Two weeks after surgery.
description: The R0 resection rate of esophagectomy.
measure: pathological complete response rate
time frame: Two weeks after surgery.
description: The rate of pathologic 1a after neoadjuvant chemotherapy.
measure: disease free survival
time frame: From the date of surgery until the date of death due to disease progression or the date of first documented disease progression whichever came first, assessed up to 24 months.
description: The 2-year disease free survival of the whole group.
measure: disease free survival rate
time frame: From the date of surgery until the date of death due to disease progression or the date of first documented disease progression whichever came first, assessed up to 24 months.
description: The 2-year disease free survival rate of the whole group.
measure: event free survival
time frame: From the date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
description: The 2-year event free survival of the whole group.
measure: event free survival rate
time frame: From the date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
description: The 2-year event free survival rate of the whole group.
measure: overall survival rate
time frame: From the 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.
description: The 2-year overall survival rate of the whole group.
measure: overall survival
time frame: From the 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.
description: The 2-year overall survival of the whole group.
measure: adverse events rate
time frame: From the date of randomization to 90 days after the last chemotherapy.
description: The incidence rate of treatment-related adverse events of the whole group assessed by CTCAE v5.0.
arm group label: PD-L1 group
arm group type: Experimental
description: All patients will receive 16 cycles of anti-PD-L1 antibody (5mg/kg, IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks).
arm group label: placebo group
arm group type: Placebo Comparator
description: All patients will receive 4 cycles of placebo ( IV, every 3 weeks) , concurrently with 4 cycles of albumin-bound paclitaxel and cisplatin (albumin-bound paclitaxel 125mg/m2 on days 1, 8 and cisplatin 75 mg/m2 on day 1 every 3 weeks).
intervention type: Drug
intervention name: anti-PD-L1 antibody
description: Patients will receive 16 cycles of anti-PD-L1 antibody 5mg/kg IV on day 1 every 3 weeks.
arm group label: PD-L1 group
other name: ZKAB001
other name: Socazolimab Injection
intervention type: Drug
intervention name: albumin bound paclitaxel
description: Patients will receive 4 cycles of albumin bound paclitaxel 125mg/m2 on days 1, 8 every 3 weeks .
arm group label: PD-L1 group
arm group label: placebo group
other name: ABRAXANE
intervention type: Drug
intervention name: cisplatin
description: Patients will receive 4 cycles of cisplatin 75mg/m2 on day 1 every 3 weeks.
arm group label: PD-L1 group
arm group label: placebo group
intervention type: Drug
intervention name: placebo
description: Patients will receive 4 cycles of placebo IV on day 1 every 3 weeks.
arm group label: placebo group
intervention type: Procedure
intervention name: radical resection of esophageal carcinoma
description: Patients will receive radical resection of esophageal carcinoma after 4 cycles of chemotherapy.
arm group label: PD-L1 group
arm group label: placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: SHUGENG GAO, MD
role: Study Director
affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College
facility: 
country: China
url: http://gco.iarc.fr/today/data/factsheets/cancers/6Oesophagus-fact-sheet.pdf.
description: GLOBOCAN 2018: oesophagus cancer fact sheet
citation: Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. doi: 10.1056/NEJM199812313392704.
PMID: 9869669
citation: Lin CC, Hsu CH, Cheng JC, Wang HP, Lee JM, Yeh KH, Yang CH, Lin JT, Cheng AL, Lee YC. Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal cancer. Ann Oncol. 2007 Jan;18(1):93-98. doi: 10.1093/annonc/mdl339. Epub 2006 Oct 6.
PMID: 17028244
citation: Polee MB, Tilanus HW, Eskens FA, Hoekstra R, Van der Burg ME, Siersema PD, Stoter G, Van der Gaast A. Phase II study of neo-adjuvant chemotherapy with paclitaxel and cisplatin given every 2 weeks for patients with a resectable squamous cell carcinoma of the esophagus. Ann Oncol. 2003 Aug;14(8):1253-7. doi: 10.1093/annonc/mdg328.
PMID: 12881388
citation: Shapiro J, van Hagen P, Lingsma HF, Wijnhoven BP, Biermann K, ten Kate FJ, Steyerberg EW, van der Gaast A, van Lanschot JJ; CROSS Study Group. Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg. 2014 Nov;260(5):807-13; discussion 813-4. doi: 10.1097/SLA.0000000000000966.
PMID: 25379852
responsible party type: Sponsor
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Neoplasms
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Antibodies