<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/NCT03787251</url>
  </required_header>
  <id_info>
    <org_study_id>Nanjing Drum Tower Hospital</org_study_id>
    <nct_id>NCT03787251</nct_id>
  </id_info>
  <brief_title>A Study of Second-line Treatment of Postoperative Recurrence and Metastasis of Esophageal Cancer Treated With Apatinib</brief_title>
  <official_title>Randomized, Open, Positive Drug Control, Multicenter Clinical Study of Second-line Treatment of Postoperative Recurrence and Metastasis of Esophageal Squamous Cell Carcinoma With Chemotherapy in Patients Treated With Apatinib Mesylate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</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>
      A study of second-line treatment of postoperative recurrence and metastasis of esophageal&#xD;
      squamous cell carcinoma after chemotherapy with apatinib mesylate&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label, multi-center, phase II clinical trial initiated by a&#xD;
      investigator to observe and evaluate the efficacy of apatinib in the treatment of patients&#xD;
      with failed first-line treatment after recurrence and metastasis of esophageal squamous cell&#xD;
      carcinoma. Effectiveness and security.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    In China, apatinib has been approved as an indication drug for esophageal squamous cell&#xD;
    carcinoma, which makes it very difficult for our clinical trial to enroll patients. We regret&#xD;
    that we failed to implement the design as planned.&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>One year from admission</time_frame>
    <description>progression-free survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>One year from admission</time_frame>
    <description>Overall Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR</measure>
    <time_frame>One year from admission</time_frame>
    <description>disease control rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>One year from admission</time_frame>
    <description>Objective Response Rate</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Esophageal Neoplasms</condition>
  <arm_group>
    <arm_group_label>experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>It is recommended that the initial dose of apatinib is 500mg po qd. Adjust the dose to 750mg po qd or maintain the original dose according to the patient's medication response for about 2 weeks. If there is grade III or above, or grade II and above non-hematologic toxicity, allow the dose to be lowered 2 times.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The chemotherapeutic drug chosen by the investigator (if not used in the previous treatment regimen, it cannot be selected).&#xD;
The choice of chemotherapy regimen is based on the medication habits of the drug delivery doctor and the specific circumstances of the patient.&#xD;
In addition, the following regimens may be selected as monotherapy or combination: docetaxel 60-75 mg/m2d1 q3w; irinotecan 150-180 mg/m2 d1 q2w until disease progression or patient decease. If the adverse event grade 3 and above Or non-hematologic toxicity of grade II and above appeared, allowing the dose to be lowered twice.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>It is recommended that the initial dose of apatinib is 500mg po qd. Adjust the dose to 750mg po qd or maintain the original dose according to the patient's medication response for about 2 weeks. If there is grade III or above, or grade II and above non-hematologic toxicity, allow the dose to be lowered 2 times.</description>
    <arm_group_label>experimental group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>The chemotherapeutic drug chosen by the investigator.</intervention_name>
    <description>The choice of chemotherapy regimen is based on the medication habits of the drug delivery doctor and the specific circumstances of the patient.&#xD;
In addition, the following regimens may be selected as monotherapy or combination: docetaxel 60-75 mg/m2d1 q3w; irinotecan 150-180 mg/m2 d1 q2w until disease progression or patient death. If grade 3 and above or non-hematologic toxicity of grade II and above adverse event appeared, allowing the dose to be lowered twice.</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathological/histological diagnosis of esophageal squamous cell carcinoma; and at&#xD;
             least one measurable lesion according to RECIST criteria (version 1.1);&#xD;
&#xD;
          -  Patients who have undergone radical resection of esophageal cancer and who have failed&#xD;
             after first-line systemic chemotherapy (which may include platinum, taxane or&#xD;
             fluorouracil) after recurrence (recurrence of postoperative adjuvant chemotherapy&#xD;
             within 6 months) Considered as first-line treatment, and the same progress in the&#xD;
             field of radiation can be seen as recurrence;&#xD;
&#xD;
          -  Age: 18-75 years old; both men and women;&#xD;
&#xD;
          -  ECOG PS Rating: 0-1 points;&#xD;
&#xD;
          -  Estimated survival period ≥ 3 months;&#xD;
&#xD;
          -  ≥ 4 weeks from the last cytotoxic drug;&#xD;
&#xD;
          -  The main organs function normally, that is, meet the following criteria:&#xD;
&#xD;
               -  Blood routine examination:&#xD;
&#xD;
                    -  HB≥90 g/L; (no blood transfusion within 14 days)&#xD;
&#xD;
                    -  ANC ≥ 1.5 × 109 / L;&#xD;
&#xD;
                    -  PLT ≥ 80 × 109 / L;&#xD;
&#xD;
               -  Biochemical examinations must meet the following criteria:&#xD;
&#xD;
                    -  ALT and AST &lt; 2.5 ULN; if there is liver metastasis, ALT and AST &lt; 5 ULN;&#xD;
&#xD;
                    -  TBIL ≤ 1.5ULN;&#xD;
&#xD;
                    -  Plasma Cr≤1.5ULN or creatinine clearance (CCr)≥60ml/min&#xD;
&#xD;
          -  Subjects volunteered to participate in the study, signed informed consent, and were&#xD;
             well-adhered to follow-up.&#xD;
&#xD;
          -  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&#xD;
             end of the study; negative serum or urine pregnancy tests within seven days prior to&#xD;
             study enrollment And must be non-lactating patients; males should agree to patients&#xD;
             who must use contraception during the study period and within 6 months after the end&#xD;
             of the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those who have used anti-tumor angiogenesis drugs to treat failure;&#xD;
&#xD;
          -  Patients with residual esophagus, residual stomach or anastomotic recurrence;&#xD;
&#xD;
          -  Unable to swallow, chronic diarrhea and intestinal obstruction, which obviously affect&#xD;
             the taking and absorption of drugs;&#xD;
&#xD;
          -  Patients with brain metastases with symptoms or symptoms controlled for less than 3&#xD;
             months;&#xD;
&#xD;
          -  Long-term unhealed wounds and fractures;&#xD;
&#xD;
          -  Have clear gastrointestinal bleeding concerns (such as local active ulcer lesions,&#xD;
             fecal occult blood above ++), history of gastrointestinal bleeding within 6 months;&#xD;
             coagulation abnormalities (PT&gt;16 s, APTT&gt;43 s, TT&gt;21 s, Fbg&lt; 2 g/L), with bleeding&#xD;
             tendency or undergoing thrombolytic or anticoagulant therapy;&#xD;
&#xD;
          -  Overactive/venous thrombosis occurred within 6 months, such as cerebrovascular&#xD;
             accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary&#xD;
             embolism;&#xD;
&#xD;
          -  Imaging shows that the tumor has invaded the important perivascular circumference or&#xD;
             that the patient is likely to invade the important blood vessels during the follow-up&#xD;
             study and cause fatal bleeding.&#xD;
&#xD;
          -  Persons with a history of psychotropic substance abuse who are unable to resolve or&#xD;
             have a mental disorder;&#xD;
&#xD;
          -  Participated in other clinical trials of anti-tumor drugs within four weeks;&#xD;
&#xD;
          -  Have a history of immunodeficiency, including HIV positive or other acquired,&#xD;
             congenital immunodeficiency disease, or a history of organ transplantation;&#xD;
&#xD;
          -  According to the investigator's judgment, there are serious concomitant illnesses that&#xD;
             compromise the safety of the patient or affect the patient's completion of the study.&#xD;
&#xD;
          -  Patients with any severe and/or uncontrolled diseases, including:&#xD;
&#xD;
               -  Blood pressure control is unreasonable (retraction pressure &gt;150mmHg, diastolic&#xD;
                  pressure &gt;100mmHg) Patients: I have myocardial ischemia or myocardial infarction&#xD;
                  above grade I, arrhythmia (including QT interval &gt;440ms) and grade I cardiac&#xD;
                  insufficiency;&#xD;
&#xD;
               -  Active or uncontrolled serious infections;&#xD;
&#xD;
               -  Liver diseases such as cirrhosis, decompensated liver disease, chronic active&#xD;
                  hepatitis;&#xD;
&#xD;
               -  Poor diabetes control (fasting blood glucose FBG&gt;10mmol/L);&#xD;
&#xD;
               -  Urine routine indicates urinary protein &gt;++, and confirmed 24-hour urine protein&#xD;
                  quantitation &gt;1.0g.&#xD;
&#xD;
          -  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>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>April 11, 2022</last_update_submitted>
  <last_update_submitted_qc>April 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</investigator_affiliation>
    <investigator_full_name>Wei Ren</investigator_full_name>
    <investigator_title>Deputy Chief Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apatinib</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/NCT03787251
org study id: Nanjing Drum Tower Hospital
nct id: NCT03787251
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
A study of second-line treatment of postoperative recurrence and metastasis of esophageal
      squamous cell carcinoma after chemotherapy with apatinib mesylate
This is a randomized, open-label, multi-center, phase II clinical trial initiated by a
      investigator to observe and evaluate the efficacy of apatinib in the treatment of patients
      with failed first-line treatment after recurrence and metastasis of esophageal squamous cell
      carcinoma. Effectiveness and security.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS
time frame: One year from admission
description: progression-free survival
measure: OS
time frame: One year from admission
description: Overall Survival
measure: DCR
time frame: One year from admission
description: disease control rate
measure: ORR
time frame: One year from admission
description: Objective Response Rate
arm group label: experimental group
arm group type: Experimental
description: It is recommended that the initial dose of apatinib is 500mg po qd. Adjust the dose to 750mg po qd or maintain the original dose according to the patient's medication response for about 2 weeks. If there is grade III or above, or grade II and above non-hematologic toxicity, allow the dose to be lowered 2 times.
arm group label: Control group
arm group type: Active Comparator
description: The chemotherapeutic drug chosen by the investigator (if not used in the previous treatment regimen, it cannot be selected).
The choice of chemotherapy regimen is based on the medication habits of the drug delivery doctor and the specific circumstances of the patient.
In addition, the following regimens may be selected as monotherapy or combination: docetaxel 60-75 mg/m2d1 q3w; irinotecan 150-180 mg/m2 d1 q2w until disease progression or patient decease. If the adverse event grade 3 and above Or non-hematologic toxicity of grade II and above appeared, allowing the dose to be lowered twice.
intervention type: Drug
intervention name: Apatinib
description: It is recommended that the initial dose of apatinib is 500mg po qd. Adjust the dose to 750mg po qd or maintain the original dose according to the patient's medication response for about 2 weeks. If there is grade III or above, or grade II and above non-hematologic toxicity, allow the dose to be lowered 2 times.
arm group label: experimental group
intervention type: Drug
intervention name: The chemotherapeutic drug chosen by the investigator.
description: The choice of chemotherapy regimen is based on the medication habits of the drug delivery doctor and the specific circumstances of the patient.
In addition, the following regimens may be selected as monotherapy or combination: docetaxel 60-75 mg/m2d1 q3w; irinotecan 150-180 mg/m2 d1 q2w until disease progression or patient death. If grade 3 and above or non-hematologic toxicity of grade II and above adverse event appeared, allowing the dose to be lowered twice.
arm group label: Control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
investigator full name: Wei Ren
investigator title: Deputy Chief Physician
mesh term: Esophageal Neoplasms
mesh term: Recurrence
mesh term: Apatinib