<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/NCT03766178</url>
  </required_header>
  <id_info>
    <org_study_id>FQX-002</org_study_id>
    <nct_id>NCT03766178</nct_id>
  </id_info>
  <brief_title>Study of Anti-PD-1 Antibody SHR-1210 Plus Nimotuzumab in the Treatment of Advanced Esophageal Squamous Cell Carcinoma</brief_title>
  <official_title>A Single-arm, Open Phase II Clinical Trial of Anti-PD-1 Antibody SHR-1210 Combined With Nimotuzumab as Second-line Treatment of 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>
  </sponsors>
  <source>The First Affiliated Hospital of Zhengzhou University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <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 anti-PD-1&#xD;
      antibody SHR-1210 combined with nimotuzumab as second-line therapy in patients with advanced&#xD;
      cancerous esophageal squamous cell carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The incidence of esophageal cancer is ranked seventh in the world, and the mortality rate&#xD;
      ranks sixth in the world. At present, the first-line treatment of advanced esophageal cancer&#xD;
      is mainly based on the combination of paclitaxel, cisplatin and fluorouracil. After the&#xD;
      failure of first-line treatment, there is no standard second-line treatment. The&#xD;
      investigators designed a single-arm, open phase II clinical trial of anti-PD-1 antibody&#xD;
      SHR-1210 combined with nimotuzumab as second-line therapy in patients with advanced cancerous&#xD;
      esophageal squamous cell carcinoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 2021</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</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>Objective Response Rate (ORR)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>From date of randomization until the date of death from any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>up to 2 year</time_frame>
    <description>From date of randomization until the date of first documented progression or date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>up to 2 year</time_frame>
    <description>Refers to the time when the tumor is first evaluated as CR or PR until the first assessment is PD (Progressive Disease) or any cause of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival(OS)</measure>
    <time_frame>up to 2 year</time_frame>
    <description>From date of randomization until the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>9-month survival rate</measure>
    <time_frame>up to 9 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-month survival rate</measure>
    <time_frame>up to 12 month</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Nimotuzumab + SHR-1210</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nimotuzumab + SHR-1210</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nimotuzumab + SHR-1210</intervention_name>
    <description>SHR-1210: 200 mg/time, intravenous injection, q2W continuous medication, a course of treatment needs 28 days. The cumulative longest medication period is 2 years.&#xD;
Nimotuzumab: 200 mg/time, intravenous injection, administered on the 1st and 8th days of each cycle, every 2 weeks is one cycle.</description>
    <arm_group_label>Nimotuzumab + SHR-1210</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18~75 years, both men and women.&#xD;
&#xD;
          2. Pathologically (histologically or cytologically) confirmed diagnosis of esophageal&#xD;
             squamous cell carcinoma (ESCC)， and locally advanced unresectable, local recurrence or&#xD;
             distant metastasis.&#xD;
&#xD;
          3. Patients undergoing first-line systemic chemotherapy (which may include platinum,&#xD;
             lavender or fluorouracil) progression or intolerance (progress in maintenance therapy&#xD;
             after first-line chemotherapy can also be included). Synchronous chemoradiotherapy for&#xD;
             postoperative recurrence or metastasis is considered as first-line treatment; For&#xD;
             radical concurrent chemoradiotherapy, neoadjuvant/adjuvant therapy (chemotherapy or&#xD;
             chemoradiotherapy), if disease progression occurs during treatment or within 6 months&#xD;
             after stopping treatment, Count it as a first-line treatment failure.&#xD;
&#xD;
          4. At least one measurable/evaluable lesion by RECIST v1.1. And the measurable lesions&#xD;
             should not have received local treatment such as radiotherapy (The lesion located in&#xD;
             the previous radiotherapy area, if confirmed to progress, and meets the RECIST 1.1&#xD;
             standard, can also be used as a target lesion).&#xD;
&#xD;
          5. EGFR immunohistochemistry or FISH detection was positive in tumor tissue samples.&#xD;
&#xD;
          6. 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;
          7. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.&#xD;
&#xD;
          8. Life expectancy of ≥ 12 weeks.&#xD;
&#xD;
          9. 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;
        10. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF)≥ normal low&#xD;
        limit (50%).&#xD;
&#xD;
        11. Women of childbearing age should agree to use contraceptives (such as intrauterine&#xD;
        devices, contraceptives or condoms) during the study period and within 6 months of the end&#xD;
        of the study; the serum or urine pregnancy test is negative within 7 days prior to study&#xD;
        enrollment, and Must be non-lactating; males should agree to use contraceptives during the&#xD;
        study period and within 6 months of the end of the study period.&#xD;
&#xD;
        12. Subjects voluntarily joined the study, signed informed consent, and were well-adhered&#xD;
        to follow-u.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. 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, thyroid&#xD;
             Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can&#xD;
             be included without any intervention after adult; asthma patients who require&#xD;
             bronchodilators for medical intervention cannot be included).&#xD;
&#xD;
          2. The patient is using immunosuppressive agents or systemic hormonal therapy for&#xD;
             immunosuppression purposes (dose &gt;10 mg/day of prednisone or other therapeutic&#xD;
             hormones) and continues to be used within 2 weeks prior to enrollment.&#xD;
&#xD;
          3. Patients who received EGFR monoclonal antibody or EGFR tyrosine kinase inhibitor;&#xD;
&#xD;
          4. Patients who received other PD-1 antibody therapy or other immunotherapy against&#xD;
             PD-1/PD-L1;&#xD;
&#xD;
          5. Patients with brain metastases with symptoms or symptom control for less than 3&#xD;
             months;&#xD;
&#xD;
          6. Patients with any severe and/or uncontrolled diseases, including patients with&#xD;
             unsatisfactory blood pressure control (systolic blood pressure ≥150 mmHg or diastolic&#xD;
             blood pressure ≥100 mmHg); patients with grade I or higher myocardial ischemia or&#xD;
             myocardial infarction, arrhythmia (including QT interval ≥ 480ms) and grade I cardiac&#xD;
             insufficiency; active or uncontrolled severe infection; liver disease such as&#xD;
             decompensated liver disease, active hepatitis B (HBV-DNA ≥ 104 copy number / ml or&#xD;
             2000 IU / ml) Or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher&#xD;
             than the lower limit of detection of the analytical method);&#xD;
&#xD;
          7. Imaging studies have shown that the tumor has invaded the important vascular&#xD;
             circumference or that the patient is likely to invade the important;&#xD;
&#xD;
          8. Pregnant or lactating women.&#xD;
&#xD;
          9. Patients with other malignant tumors within 5 years（Except for skin basal cell&#xD;
             carcinoma and cervical carcinoma in situ that have been cured).&#xD;
&#xD;
         10. Patients with a history of psychotropic substance abuse who are unable to quit or have&#xD;
             a mental disorder.&#xD;
&#xD;
         11. Patients who have participated in other drug clinical trials within four weeks.&#xD;
&#xD;
         12. According to the investigator's judgment, the patients with concomitant diseases that&#xD;
             seriously endanger the safety of the patient or affect the patient's completion of the&#xD;
             study.&#xD;
&#xD;
         13. Researchers believe 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, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital of Zhengzhou University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Feng Wang, Doctor</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>July 2021</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>July 6, 2021</last_update_submitted>
  <last_update_submitted_qc>July 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2021</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>Director</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nimotuzumab</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/NCT03766178
org study id: FQX-002
nct id: NCT03766178
lead sponsor: 
has dmc: No
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 anti-PD-1
      antibody SHR-1210 combined with nimotuzumab as second-line therapy in patients with advanced
      cancerous esophageal squamous cell carcinoma.
The incidence of esophageal cancer is ranked seventh in the world, and the mortality rate
      ranks sixth in the world. At present, the first-line treatment of advanced esophageal cancer
      is mainly based on the combination of paclitaxel, cisplatin and fluorouracil. After the
      failure of first-line treatment, there is no standard second-line treatment. The
      investigators designed a single-arm, open phase II clinical trial of anti-PD-1 antibody
      SHR-1210 combined with nimotuzumab as second-line therapy in patients with advanced cancerous
      esophageal squamous cell carcinoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: up to 1 year
description: From date of randomization until the date of death from any cause
measure: Disease Control Rate (DCR)
time frame: up to 1 year
description: Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD)
measure: Progression-free Survival (PFS)
time frame: up to 2 year
description: From date of randomization until the date of first documented progression or date of death from any cause
measure: Duration of response (DOR)
time frame: up to 2 year
description: Refers to the time when the tumor is first evaluated as CR or PR until the first assessment is PD (Progressive Disease) or any cause of death.
measure: Time to response (TTR)
time frame: up to 1 year
measure: Overall survival(OS)
time frame: up to 2 year
description: From date of randomization until the date of death from any cause
measure: 9-month survival rate
time frame: up to 9 month
measure: 12-month survival rate
time frame: up to 12 month
arm group label: Nimotuzumab + SHR-1210
arm group type: Experimental
description: Nimotuzumab + SHR-1210
intervention type: Drug
intervention name: Nimotuzumab + SHR-1210
description: SHR-1210: 200 mg/time, intravenous injection, q2W continuous medication, a course of treatment needs 28 days. The cumulative longest medication period is 2 years.
Nimotuzumab: 200 mg/time, intravenous injection, administered on the 1st and 8th days of each cycle, every 2 weeks is one cycle.
arm group label: Nimotuzumab + SHR-1210
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Feng Wang, Doctor
role: Principal Investigator
affiliation: The First Affiliated Hospital of Zhengzhou University
last name: Feng Wang, Doctor
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: Director
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Nimotuzumab