<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/NCT04471480</url>
  </required_header>
  <id_info>
    <org_study_id>TCAC-ESCC-01</org_study_id>
    <nct_id>NCT04471480</nct_id>
  </id_info>
  <brief_title>TC Plus PD-1 Inhibitors Combined With Anlotinib for Advanced Advanced Esophageal Cancer</brief_title>
  <acronym>TC</acronym>
  <official_title>Paclitaxel and Carboplatin Plus PD-1 Inhibitors Combined With Anlotinib for Advanced Esophageal Cancer(ESCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dong Wang</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Third Military Medical 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>
      A Controlled Clinical Study of TC/PD-1 Inhibitors Combined With anlotinib as First-line&#xD;
      Treatment for Advanced ESCC&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The incidence rate of esophageal cancer is high in China and mainly squamous cell carcinoma.&#xD;
      In recent years, although the level of surgery, radiotherapy and chemotherapy of esophageal&#xD;
      cancer has improved, and studies have confirmed the role of anlotinib and PD-1 mAb in the&#xD;
      posterior line treatment of esophageal squamous cell carcinoma, the prognosis of esophageal&#xD;
      cancer is still not ideal. How to expand the clinical benefits of immunotherapy in esophageal&#xD;
      cancer has become a research hotspot. Recent studies have shown that PD-1 mAb combined with&#xD;
      other therapies with different mechanisms can improve the efficacy of immunotherapy. In the&#xD;
      impawer150 study, platinum containing dual drug chemotherapy plus anti angiogenesis therapy&#xD;
      combined with immunotherapy showed statistically and clinically significant PFS benefits in&#xD;
      the first-line treatment of advanced non-small-cell lung cancer, which provides a new choice&#xD;
      for the first-line treatment of advanced non-small-cell lung cancer. So far, there is no&#xD;
      report on the first-line treatment of advanced esophageal squamous cell carcinoma with&#xD;
      platinum containing dual drug chemotherapy plus anti angiogenesis drugs combined with&#xD;
      immunotherapy. The purpose of this study is to evaluate the efficacy of cisplatin plus&#xD;
      cisplatin in the treatment of advanced esophageal cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 1, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel 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>approximately 18 months</time_frame>
    <description>complete response(CR)+partial response(PR) according to RECIST 1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>overall survival (OS)</measure>
    <time_frame>approximately 36 months</time_frame>
    <description>overall survival is defined as the time from randomization to death from any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>progression-free survival(PFS)</measure>
    <time_frame>approximately 36 months</time_frame>
    <description>progression-free survival is defined as the time from enrollment to the date of first document disease progression or death from any cause</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>ESCC</condition>
  <arm_group>
    <arm_group_label>group A，TCCA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>paclitaxel for Injection 175 mg/m2,IV, d1/paclitaxel for Injection (Albumin Bound) 260mg/m2,IV, d1, q3w +carboplatin AUC 4-6,IV, d12,q3w +anlotinib 10mg, PO, d1-14, q3w +camrelizumab 200 mg, IV, d1, q3w, after the treatment for 4-6 cycles, camrelizumab plus anlotinib for maintenance therapy until PD or intolerable toxicity</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group B，TCC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>paclitaxel for Injection 175 mg/m2,IV, d1/paclitaxel for Injection (Albumin Bound) 260mg/m2,IV, d1, q3w +carboplatin AUC 4-6,IV, d12,q3w +camrelizumab 200 mg, IV, d1, q3w, after the treatment for 4-6 cycles, camrelizumab for maintenance therapy until PD or intolerable toxicity</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group C，TC</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>paclitaxel for Injection 175 mg/m2,IV, d1/paclitaxel for Injection (Albumin Bound) 260mg/m2,IV, d1, q3w +carboplatin AUC 4-6,IV, d12,q3w</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TC/PD-1 inhibitor/anlotinib</intervention_name>
    <description>chemotherapy and immunotherapy plus antiangiogenic therapy</description>
    <arm_group_label>group A，TCCA</arm_group_label>
    <arm_group_label>group B，TCC</arm_group_label>
    <arm_group_label>group C，TC</arm_group_label>
    <other_name>TC/PD-1 inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients volunteered to participate in the study and signed the informed consent;&#xD;
&#xD;
          2. Age 18-75, both male and female;&#xD;
&#xD;
          3. Histologically or cytologically confirmed advanced or metastatic (stage IIIB, III C or&#xD;
             IV) ESCC .&#xD;
&#xD;
          4. At least one measurable lesion according to RECIST 1.1,which should not be treated&#xD;
             locally, such as radiotherapy.&#xD;
&#xD;
          5. ECOG PS 0-1- Page 3 of 5 [DRAFT] -&#xD;
&#xD;
          6. Expected survival ≥ 3 months&#xD;
&#xD;
          7. Patients who never received systemic therapy in the past, including radiotherapy&#xD;
             ,chemotherapy, targeted therapy and immunotherapy , or patients who relapsed more than&#xD;
             6 months after adjuvant chemotherapy.&#xD;
&#xD;
          8. The main organ functions accorded with the following criteria within 7 days before&#xD;
             treatment:&#xD;
&#xD;
        (1)Blood routine examination ( without blood transfusion in 14 days): hemoglobin (HB) ≥ 90&#xD;
        g/L; neutrophil absolute value (ANC) ≥ 1.5 *109/L; platelet (PLT) ≥80 *109/L.&#xD;
&#xD;
        (2) Biochemical tests should meet the following criteria: 1) total bilirubin (TBIL) ≤1.5&#xD;
        times of upper limit of normal (ULN); 2) alanine aminotransferase (ALT) and aspartate&#xD;
        aminotransferase (AST) ≤2.5 *ULN, if accompanied by liver metastasis, ALT and AST ≤ 5* ULN;&#xD;
        3) serum creatinine (Cr) ≤ 1.5* ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;4) Serum&#xD;
        albumin (≥35g/L). (3) Doppler echocardiography: left ventricular ejection fraction (LVEF)&#xD;
        ≥the low limit of normal value (50%).&#xD;
&#xD;
        9 Tissue samples should be provided for biomarker analysis (such as PD-L1 ) Patients who&#xD;
        could not provide new tissues could provide 5-8 paraffin sections of 3-5 μm by archival&#xD;
        preservation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Severe allergic reactions to humanized antibodies or fusion proteins in the past&#xD;
&#xD;
          2. known to have hypersensitivity to any component contained in Endostar or antibody&#xD;
             preparations;&#xD;
&#xD;
          3. Diagnosed of immunodeficiency or received systemic glucocorticoid therapy or any other&#xD;
             form of immunosuppressive therapy within 14 days before the study, allowing&#xD;
             physiological doses of glucocorticoids (≤10mg/day prednisone or equivalent);&#xD;
&#xD;
          4. Patients with active, known or suspected autoimmune diseases. Patients with type I&#xD;
             diabetes, hypothyroidism requiring hormone replacement therapy, skin disorders&#xD;
             requiring no systemic treatment(such as vitiligo, psoriasis or alopecia). Patients who&#xD;
             would not triggers can be included.&#xD;
&#xD;
          5. Serious heart disease, include congestive heart failure, uncontrollable high-risk&#xD;
             arrhythmia, unstable angina pectoris, myocardial infarction, and severe valvular&#xD;
             disease.&#xD;
&#xD;
          6. Patients treated targeted drugs such as bevacizumab, sunitinib, sorafenib, imatinib,&#xD;
             famitinib, regiffenil, apatinib and anlotinib&#xD;
&#xD;
          7. Patients recieved systemic antineoplastic therapy, including cytotoxic therapy, signal&#xD;
             transduction inhibitors, immunotherapy (or mitomycin C within 6 weeks before the&#xD;
             grouping),recieved over-extended-field radiotherapy (EF-RT) within 4 weeks before the&#xD;
             grouping or limited-field radiotherapy to evaluate the tumor lesions within 2 weeks&#xD;
             before the grouping&#xD;
&#xD;
          8. Positive hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus antibody&#xD;
             (HCV Ab), indicating acute or chronic infection.&#xD;
&#xD;
          9. Patients with active pulmonary tuberculosis (TB) infection judged by chest X-ray&#xD;
             examination, sputum examination and clinical physical examination. Patients with&#xD;
             active pulmonary tuberculosis infection in the previous year should be excluded even&#xD;
             if they have been treated; Patients with active pulmonary tuberculosis infection more&#xD;
             than a year ago should also be excluded unless the course and type of antituberculosis&#xD;
             treatment previously were appropriate.&#xD;
&#xD;
         10. Patients with brain metastases with symptoms or symptoms controlling less than 2&#xD;
             months&#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_contact>
    <last_name>Dong Wang, PH.D</last_name>
    <phone>86-23-68757181</phone>
    <email>dongwang64@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dong Wang, PH.D</last_name>
    <phone>13678428206</phone>
    <email>dongwang64@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Daping Hospital, Third Military Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400042</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Dong Wang, PH.D.</last_name>
      <phone>86-23-68757151</phone>
      <email>dongwang64@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Dong Wang, PH.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 12, 2020</study_first_submitted>
  <study_first_submitted_qc>July 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>July 12, 2020</last_update_submitted>
  <last_update_submitted_qc>July 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Third Military Medical University</investigator_affiliation>
    <investigator_full_name>Dong Wang</investigator_full_name>
    <investigator_title>Head of Oncology</investigator_title>
  </responsible_party>
  <keyword>PD-1</keyword>
  <keyword>anlotinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immune Checkpoint Inhibitors</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/NCT04471480
org study id: TCAC-ESCC-01
nct id: NCT04471480
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A Controlled Clinical Study of TC/PD-1 Inhibitors Combined With anlotinib as First-line
      Treatment for Advanced ESCC
The incidence rate of esophageal cancer is high in China and mainly squamous cell carcinoma.
      In recent years, although the level of surgery, radiotherapy and chemotherapy of esophageal
      cancer has improved, and studies have confirmed the role of anlotinib and PD-1 mAb in the
      posterior line treatment of esophageal squamous cell carcinoma, the prognosis of esophageal
      cancer is still not ideal. How to expand the clinical benefits of immunotherapy in esophageal
      cancer has become a research hotspot. Recent studies have shown that PD-1 mAb combined with
      other therapies with different mechanisms can improve the efficacy of immunotherapy. In the
      impawer150 study, platinum containing dual drug chemotherapy plus anti angiogenesis therapy
      combined with immunotherapy showed statistically and clinically significant PFS benefits in
      the first-line treatment of advanced non-small-cell lung cancer, which provides a new choice
      for the first-line treatment of advanced non-small-cell lung cancer. So far, there is no
      report on the first-line treatment of advanced esophageal squamous cell carcinoma with
      platinum containing dual drug chemotherapy plus anti angiogenesis drugs combined with
      immunotherapy. The purpose of this study is to evaluate the efficacy of cisplatin plus
      cisplatin in the treatment of advanced esophageal cancer.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: objective response rate(ORR)
time frame: approximately 18 months
description: complete response(CR)+partial response(PR) according to RECIST 1.1
measure: overall survival (OS)
time frame: approximately 36 months
description: overall survival is defined as the time from randomization to death from any cause
measure: progression-free survival(PFS)
time frame: approximately 36 months
description: progression-free survival is defined as the time from enrollment to the date of first document disease progression or death from any cause
arm group label: group A，TCCA
arm group type: Experimental
description: paclitaxel for Injection 175 mg/m2,IV, d1/paclitaxel for Injection (Albumin Bound) 260mg/m2,IV, d1, q3w +carboplatin AUC 4-6,IV, d12,q3w +anlotinib 10mg, PO, d1-14, q3w +camrelizumab 200 mg, IV, d1, q3w, after the treatment for 4-6 cycles, camrelizumab plus anlotinib for maintenance therapy until PD or intolerable toxicity
arm group label: group B，TCC
arm group type: Experimental
description: paclitaxel for Injection 175 mg/m2,IV, d1/paclitaxel for Injection (Albumin Bound) 260mg/m2,IV, d1, q3w +carboplatin AUC 4-6,IV, d12,q3w +camrelizumab 200 mg, IV, d1, q3w, after the treatment for 4-6 cycles, camrelizumab for maintenance therapy until PD or intolerable toxicity
arm group label: group C，TC
arm group type: Other
description: paclitaxel for Injection 175 mg/m2,IV, d1/paclitaxel for Injection (Albumin Bound) 260mg/m2,IV, d1, q3w +carboplatin AUC 4-6,IV, d12,q3w
intervention type: Drug
intervention name: TC/PD-1 inhibitor/anlotinib
description: chemotherapy and immunotherapy plus antiangiogenic therapy
arm group label: group A，TCCA
arm group label: group B，TCC
arm group label: group C，TC
other name: TC/PD-1 inhibitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dong Wang, PH.D
phone: 86-23-68757181
email: dongwang64@hotmail.com
last name: Dong Wang, PH.D
phone: 13678428206
email: dongwang64@hotmail.com
facility: 
contact: 
investigator: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Third Military Medical University
investigator full name: Dong Wang
investigator title: Head of Oncology
mesh term: Esophageal Neoplasms
mesh term: Immune Checkpoint Inhibitors
sharing ipd: Undecided