<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/NCT03817658</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1210--01</org_study_id>
    <nct_id>NCT03817658</nct_id>
  </id_info>
  <brief_title>A Phase II Study of SHR-1210 vs Placebo as Consolidation Chemotherapy After Radical Concurrent Chemoradiotherapy in Locally Advanced ESCC</brief_title>
  <official_title>A Phase II Clinical Trial of Anti-PD-1 Antibody SHR-1210 Versus Placebo as Consolidation Chemotherapy After Radical Concurrent Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The First Affiliated Hospital of Zhengzhou University</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>
      The purpose of this study is to observe and evaluate the efficacy and safety of SHR-1210 vs&#xD;
      placebo as consolidation chemotherapy after radical concurrent chemoradiotherapy for&#xD;
      unresectable locally advanced ESCC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In China, the incidence of esophageal cancer has declined in recent years, but the mortality&#xD;
      rate has been ranked fourth. Morbidity and mortality were ranked sixth and fourth in all&#xD;
      malignancies, respectively. Therefore, esophageal cancer has always been a major malignant&#xD;
      tumor that threatens the health of our residents. We designed a multicenter, randomized,&#xD;
      double-blind, open-label phase II clinical trial of anti-PD-1 antibody SHR-1210 versus&#xD;
      placebo as consolidation chemotherapy (CCT) after radical concurrent chemoradiotherapy for&#xD;
      unresectable locally advanced esophageal squamous cell carcinoma (ESCC).The purpose of this&#xD;
      study is to observe and evaluate the efficacy and safety of SHR-1210 vs placebo as&#xD;
      consolidation chemotherapy after radical concurrent chemoradiotherapy for unresectable&#xD;
      locally advanced ESCC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 2019</start_date>
  <completion_date type="Anticipated">October 2021</completion_date>
  <primary_completion_date type="Anticipated">October 2020</primary_completion_date>
  <phase>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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS</measure>
    <time_frame>up to 2 year</time_frame>
    <description>Evaluation of anti-PD-1 antibody SHR-1210 for progression-free survival in patients with locally advanced esophageal squamous cell carcinoma who did not develop disease after concurrent chemoradiotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OS</measure>
    <time_frame>up to 2 year</time_frame>
    <description>From date of randomization until the date of death from any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>up to 2 year</time_frame>
    <description>Evaluation of the objective response rate of anti-PD-1 antibody SHR-1210 versus placebo in patients with locally advanced esophageal squamous cell carcinoma who had no disease progression after concurrent chemoradiotherapy(RECIST 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR</measure>
    <time_frame>up to 2 year</time_frame>
    <description>defined as the time from the first determination of an objective response until the first documentation of progression assessed by BIRC per RECIST v1.1 or death, whichever comes first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life (HRQoL)</measure>
    <time_frame>up to 2 year</time_frame>
    <description>assessment of the patient's overall health status using European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life (HRQoL)</measure>
    <time_frame>up to 2 year</time_frame>
    <description>assessment of the patient's overall health status using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer specific module (EORTC QLQ-OES18).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life (HRQoL)</measure>
    <time_frame>up to 2 year</time_frame>
    <description>assessment of the patient's overall health status using the generic health state instrument European Quality of Life- 5 Dimensions (EuroQol 5D EQ-5D-5L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence and severity of adverse events (AEs)</measure>
    <time_frame>up to 2 year</time_frame>
    <description>according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">725</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>SHR-1210</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR-1210</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR-1210</intervention_name>
    <description>First stage：&#xD;
Concurrent chemoradiotherapy:&#xD;
Cisplatin：25-30mg/m2 ivgtt d1;Capecitabine：800mg/m2, bid d1-5，qw，5weeks；Synchronous radiotherapy：1.8-2Gy/d，5d/W，45-50Gy。 Consolidation treatment： Cisplatin： 60-75mg/m2 ivgtt d1 Capecitabine：1000mg/m2, bid d1-14，q3w 6weeks。&#xD;
Second stage:&#xD;
SHR-1210 was administered intravenously (no prophylactic use), a fixed dose of 200 mg, and 3 mg/kg for subjects with a baseline weight &lt;50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 12 months.</description>
    <arm_group_label>SHR-1210</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>First stage：&#xD;
Concurrent chemoradiotherapy:&#xD;
Cisplatin：25-30mg/m2 ivgtt d1;Capecitabine：800mg/m2, bid d1-5，qw，5weeks；Synchronous radiotherapy：1.8-2Gy/d，5d/W，45-50Gy。 Consolidation treatment： Cisplatin： 60-75mg/m2 ivgtt d1 Capecitabine：1000mg/m2, bid d1-14，q3w 6weeks。&#xD;
Second stage:&#xD;
Placebo was administered intravenously (no prophylactic use), a fixed dose of 200 mg, and 3 mg/kg for subjects with a baseline weight &lt;50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 12 months.</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-75 years old, both men and women;&#xD;
&#xD;
          2. Histology confirmed as esophageal squamous cell carcinoma;&#xD;
&#xD;
          3. T1bN+M0, T2N0-2M0 local progress period;&#xD;
&#xD;
          4. According to RECIST 1.1, at least one measurable lesion;&#xD;
&#xD;
          5. Tissue samples shall be provided for biomarker analysis, preferably newly acquired&#xD;
             tissues, and patients who are unable to provide newly acquired tissues may provide 5-8&#xD;
             pieces of 5um thick paraffin sections that are archived and preserved;&#xD;
&#xD;
          6. ECOG: 0~1;&#xD;
&#xD;
          7. Expected survival period ≥ 12 weeks;&#xD;
&#xD;
          8. The main organs function normally, that is, the following criteria are met:&#xD;
&#xD;
        (1) Blood routine examination:&#xD;
&#xD;
          1. HB≥90g/L;&#xD;
&#xD;
          2. ANC ≥ 1.5 × 109 / L;&#xD;
&#xD;
          3. PLT ≥ 80 × 109 / L; (2) Biochemical examination:&#xD;
&#xD;
        a. ALB ≥ 30g / L; b. ALT and AST ≤ 2.5ULN; if there is liver metastasis, ALT and AST ≤&#xD;
        5ULN; c. TBIL ≤ 1.5ULN; d. plasma Cr ≤ 1.5ULN or creatinine clearance (CCr) ≥ 60ml / min;&#xD;
        9. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low&#xD;
        limit (50%); 10. Women of childbearing age should agree to use contraceptives (such as&#xD;
        intrauterine devices, contraceptives or condoms) during the study period and within 6&#xD;
        months after the end of the study; negative serum or urine pregnancy test within 7 days&#xD;
        prior to study enrollment And must be non-lactating patients; males should agree to&#xD;
        patients who must use contraception during the study period and within 6 months after the&#xD;
        end of the study period; 11. Subjects voluntarily joined the study, signed informed&#xD;
        consent, and were well-adhered to follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Does not meet the above inclusion criteria;&#xD;
&#xD;
          2. Those who are allergic or metabolically dying of capecitabine and cisplatin;&#xD;
&#xD;
          3. The patient has any active autoimmune disease or a history of autoimmune disease (such&#xD;
             as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia,&#xD;
             uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis,&#xD;
             Hyperthyroidism; patients with vitiligo; Asthma has been completely relieved in&#xD;
             childhood, and patients who do not need any intervention after adulthood can be&#xD;
             included; asthma patients who require bronchodilators for medical intervention cannot&#xD;
             be included);&#xD;
&#xD;
          4. The patient is using immunosuppressive agents or systemic hormonal therapy for&#xD;
             immunosuppressive purposes (dose &gt; 10 mg/day of prednisone or other therapeutic&#xD;
             hormones) and continues to be used for 2 weeks prior to enrollment;&#xD;
&#xD;
          5. Radiotherapy contraindications;&#xD;
&#xD;
          6. Patients with any severe and/or uncontrolled diseases;&#xD;
&#xD;
          7. Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150mmHg&#xD;
             or diastolic blood pressure ≥100 mmHg); myocardial ischemia or myocardial infarction&#xD;
             with grade I or above, arrhythmia (including QT interval ≥480ms) and grade I cardiac&#xD;
             insufficiency;&#xD;
&#xD;
          8. Active or uncontrolled serious infections;&#xD;
&#xD;
          9. Liver diseases such as decompensated liver disease, active hepatitis B (HBV-DNA ≥ 104&#xD;
             copies/ml or 2000 IU/ml) or hepatitis C (positive hepatitis C antibody, and HCV-RNA is&#xD;
             higher than the lower limit of detection of the analytical method);&#xD;
&#xD;
         10. Urine routine indicates that urine protein ≥ ++, and confirmed 24-hour urine protein&#xD;
             quantitation &gt; 1.0g;&#xD;
&#xD;
         11. Imaging shows that the tumor has invaded the important perivascular circumference or&#xD;
             that the patient is likely to invade the important blood vessels and cause fatal&#xD;
             bleeding during the follow-up study;&#xD;
&#xD;
         12. Pregnant or lactating women;&#xD;
&#xD;
         13. Patients with other malignancies within 5 years (except for basal cell carcinoma and&#xD;
             cervical carcinoma in situ) that have been cured;&#xD;
&#xD;
         14. Patients with a history of psychotropic substance abuse who are unable to quit or have&#xD;
             a mental disorder;&#xD;
&#xD;
         15. Patients who have participated in other drug clinical trials within four weeks;&#xD;
&#xD;
         16. At the discretion of the investigator, there are patients with serious concomitant&#xD;
             disease that compromises patient safety or affects the patient's completion of the&#xD;
             study;&#xD;
&#xD;
         17. The investigator believes that it is not suitable for inclusion.&#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>Feng Wang</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital of Zhengzhou University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Feng Wang</last_name>
    <phone>13938244776</phone>
    <email>fengw010@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Zhengzhou University</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450052</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>January 23, 2019</last_update_submitted>
  <last_update_submitted_qc>January 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The First Affiliated Hospital of Zhengzhou University</investigator_affiliation>
    <investigator_full_name>Feng Wang</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <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>
  <!-- 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/NCT03817658
org study id: SHR-1210--01
nct id: NCT03817658
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to observe and evaluate the efficacy and safety of SHR-1210 vs
      placebo as consolidation chemotherapy after radical concurrent chemoradiotherapy for
      unresectable locally advanced ESCC.
In China, the incidence of esophageal cancer has declined in recent years, but the mortality
      rate has been ranked fourth. Morbidity and mortality were ranked sixth and fourth in all
      malignancies, respectively. Therefore, esophageal cancer has always been a major malignant
      tumor that threatens the health of our residents. We designed a multicenter, randomized,
      double-blind, open-label phase II clinical trial of anti-PD-1 antibody SHR-1210 versus
      placebo as consolidation chemotherapy (CCT) after radical concurrent chemoradiotherapy for
      unresectable locally advanced esophageal squamous cell carcinoma (ESCC).The purpose of this
      study is to observe and evaluate the efficacy and safety of SHR-1210 vs placebo as
      consolidation chemotherapy after radical concurrent chemoradiotherapy for unresectable
      locally advanced ESCC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS
time frame: up to 2 year
description: Evaluation of anti-PD-1 antibody SHR-1210 for progression-free survival in patients with locally advanced esophageal squamous cell carcinoma who did not develop disease after concurrent chemoradiotherapy
measure: OS
time frame: up to 2 year
description: From date of randomization until the date of death from any cause
measure: ORR
time frame: up to 2 year
description: Evaluation of the objective response rate of anti-PD-1 antibody SHR-1210 versus placebo in patients with locally advanced esophageal squamous cell carcinoma who had no disease progression after concurrent chemoradiotherapy(RECIST 1.1)
measure: DOR
time frame: up to 2 year
description: defined as the time from the first determination of an objective response until the first documentation of progression assessed by BIRC per RECIST v1.1 or death, whichever comes first
measure: Health-Related Quality of Life (HRQoL)
time frame: up to 2 year
description: assessment of the patient's overall health status using European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30).
measure: Health-Related Quality of Life (HRQoL)
time frame: up to 2 year
description: assessment of the patient's overall health status using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer specific module (EORTC QLQ-OES18).
measure: Health-Related Quality of Life (HRQoL)
time frame: up to 2 year
description: assessment of the patient's overall health status using the generic health state instrument European Quality of Life- 5 Dimensions (EuroQol 5D EQ-5D-5L).
measure: The incidence and severity of adverse events (AEs)
time frame: up to 2 year
description: according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03
arm group label: SHR-1210
arm group type: Experimental
description: SHR-1210
arm group label: placebo
arm group type: Placebo Comparator
description: placebo
intervention type: Drug
intervention name: SHR-1210
description: First stage：
Concurrent chemoradiotherapy:
Cisplatin：25-30mg/m2 ivgtt d1;Capecitabine：800mg/m2, bid d1-5，qw，5weeks；Synchronous radiotherapy：1.8-2Gy/d，5d/W，45-50Gy。 Consolidation treatment： Cisplatin： 60-75mg/m2 ivgtt d1 Capecitabine：1000mg/m2, bid d1-14，q3w 6weeks。
Second stage:
SHR-1210 was administered intravenously (no prophylactic use), a fixed dose of 200 mg, and 3 mg/kg for subjects with a baseline weight <50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 12 months.
arm group label: SHR-1210
intervention type: Drug
intervention name: Placebo
description: First stage：
Concurrent chemoradiotherapy:
Cisplatin：25-30mg/m2 ivgtt d1;Capecitabine：800mg/m2, bid d1-5，qw，5weeks；Synchronous radiotherapy：1.8-2Gy/d，5d/W，45-50Gy。 Consolidation treatment： Cisplatin： 60-75mg/m2 ivgtt d1 Capecitabine：1000mg/m2, bid d1-14，q3w 6weeks。
Second stage:
Placebo was administered intravenously (no prophylactic use), a fixed dose of 200 mg, and 3 mg/kg for subjects with a baseline weight <50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 12 months.
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Feng Wang
role: Principal Investigator
affiliation: The First Affiliated Hospital of Zhengzhou University
last name: Feng Wang
phone: 13938244776
email: fengw010@163.com
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: The First Affiliated Hospital of Zhengzhou University
investigator full name: Feng Wang
investigator title: Doctor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma