<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/NCT02976896</url>
  </required_header>
  <id_info>
    <org_study_id>Poetry-1</org_study_id>
    <nct_id>NCT02976896</nct_id>
  </id_info>
  <brief_title>Apatinib for Esophageal Squamous Cell Cancer After the Failure of Standard Treatment</brief_title>
  <acronym>Poetry-1</acronym>
  <official_title>Efficacy and Safety of Apatinib Mesylate in Recurrent/Metastatic Esophageal Squamous Cell Carcinoma After the Failure of Conventional Treatment: a Phase II Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yuhong Li</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We conduct the phase II clinical trial to further explore the efficacy and safety of Apatinib&#xD;
      Mesylate in treating recurrent or metastatic esophageal squamous cell carcinoma after the&#xD;
      failure of conventional treatments. An exploratory molecular marker analysis will be&#xD;
      performed in order to find out the beneficial population of Apatinib Mesylate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Esophageal cancer is one of the most common malignant tumor in China. In Asian countries,&#xD;
      esophageal squamous cell carcinoma is the main pathological type of esophageal carcinoma.&#xD;
      Prognosis of esophageal squamous cell carcinoma is usually poor and surgery is the only&#xD;
      radical treatment. Cisplatin (DDP, cisplatin), 5 - Fluorouracil (5 - Fluorouracil, 5 - FU)&#xD;
      and taxane are the most adopted chemotherapy agents, with efficacy rates of 33%-40% as&#xD;
      first-line treatment for metastatic or recurrent esophageal squamous carcinoma and a median&#xD;
      overall survival of 6-10 months. New agents were needed. Apatinib Mesylate is a small&#xD;
      molecule VEGFR tyrosine kinase inhibitor. The anti-tumor mechanism of Apatinib is inhibiting&#xD;
      angiogenesis in malignancy by inhibiting VEGFR. Apatinib Mesylate was approved by CFDA (China&#xD;
      Food and Drug Administration) for the treatment of advanced gastric cancer. In the previous&#xD;
      clinical practice, we observed that part of the patients with esophageal squamous cell&#xD;
      carcinoma were resistant to conventional treatments benefited from Apatinib Mesylate. Based&#xD;
      on the research situation mentioned above, we decided to conduct a phase II clinical trial to&#xD;
      further explore the efficacy and safety of Apatinib Mesylate in treating recurrent or&#xD;
      metastatic esophageal squamous cell carcinoma after the failure of conventional treatments.&#xD;
      An exploratory molecular marker analysis will be performed in order to find out the&#xD;
      beneficial population of Apatinib Mesylate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2016</start_date>
  <completion_date type="Actual">December 2022</completion_date>
  <primary_completion_date type="Actual">December 2019</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>Disease control rate</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>Each follow up vist, assessed up to 12 months</time_frame>
    <description>Safety evaluation according to the CTCAE4.0 standard, once every 1 cycle assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life using EORTC QLQ C30 - scale</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
    <description>Life quality evaluation using EORTC QLQ C30 - scale，once every 1 cycle assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life using esophageal special scale QLQ - OES18</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
    <description>Life quality evaluation using esophageal special scale QLQ - OES18, once every 1 cycle assessment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Apatinib Mesylate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive Apatinib Mesylate at 500mg/times,oral one times daily for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib Mesylate</intervention_name>
    <description>Patients will receive Apatinib Mesylate at 500mg/times,oral one times daily for 28 days.</description>
    <arm_group_label>Apatinib Mesylate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients, age:18-75 years old.&#xD;
&#xD;
          2. The ECOG physical status score: 0 to 2.&#xD;
&#xD;
          3. Confirmed by histology of recurrent or metastatic esophageal squamous cell carcinoma.&#xD;
&#xD;
          4. Patients who previously received at least fluorouracil, platin or taxane-based&#xD;
             palliative chemotherapy but failed(including patients who developed disease&#xD;
             progression within half of a year after finishing their adjuvant or neoadjuvant&#xD;
             chemotherapy) and patients who are intolerable or refuse to receive chemotherapy of&#xD;
             agents mentioned above and develop disease progression within 2 months.&#xD;
&#xD;
          5. Never received treatment of apatinib or any other anti-angiogenesis agent, such as&#xD;
             sorafenib, sunitinib, bevacizumab, endostar etc.&#xD;
&#xD;
          6. Lesions can be measured at single diameter by thoracic or abdominal computed&#xD;
             tomography (CT) or magnetic resonance (MRI).Conventional methods should set at least&#xD;
             20mm as diameter or spiral CT 10 mm. Patients with increased or new lesions in&#xD;
             radiotherapy area can be enrolled in the trial.&#xD;
&#xD;
          7. Expected survival ≥ 3 months.&#xD;
&#xD;
          8. If the subject have received surgery, the operative wound should be completely healed&#xD;
             and without bleeding tendency.&#xD;
&#xD;
          9. Baseline of blood routine and biochemical routine should meet the following criteria:&#xD;
&#xD;
               -  ANC≥1.5×10^9/L（1500/mm3）&#xD;
&#xD;
               -  PLT≥75×10^9/L&#xD;
&#xD;
               -  Hb≥9 g/dL&#xD;
&#xD;
               -  Serum bilirubin levels no higher than 2 times the upper limit of normal value.&#xD;
&#xD;
               -  AST and ALT no higher than 2.5 times the upper limit of normal value(no higher&#xD;
                  than 5 times the upper limit of normal value when patients developed liver&#xD;
                  metastasis).&#xD;
&#xD;
               -  Serum creatinine no higher than 1.5 times the upper limit of normal value.&#xD;
&#xD;
         10. No malabsorption or other gastrointestinal disorders that will affect drugs&#xD;
             absorption.&#xD;
&#xD;
         11. No severe complications such as active digestive tract hemorrhage, perforation,&#xD;
             jaundice, gastrointestinal obstruction, non-cancerous fever &gt; 38 ℃.&#xD;
&#xD;
         12. Patients should be voluntary to the trial and provide with signed informed consent.&#xD;
&#xD;
         13. Patients should have good compliance and cooperate with the evaluation of efficacy and&#xD;
             adverse events and follow-ups according to the research plan.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of gastrointestinal bleeding tendency including: local active ulcer lesions&#xD;
             with occult blood (+ +); melena and haematemesis within 2 months; possibilities of&#xD;
             digestive tract hemorrhage.&#xD;
&#xD;
          2. Evidence of hypertension that could not be controlled by drugs (SBP&gt;140 mmHg, DBP&gt;90&#xD;
             mmHg), grade I coronary heart disease, grade I arrhythmia(including QT interval&#xD;
             prolonged by 450ms in male and 470ms in female) and grade I heart failure.&#xD;
&#xD;
          3. Evidence of severe postoperative complications including intestinal obstruction,&#xD;
             anastomotic fistula, pancreatic fistula and anastomotic stenosis.&#xD;
&#xD;
          4. Evidence of urine protein ≥ (++) and 24 hours urinary protein quantitation &gt;1.0 g.&#xD;
&#xD;
          5. Fractures unhealed for long term or incompletely healed.&#xD;
&#xD;
          6. Evidence of immunodeficiency disease, or other acquired or congenital immunodeficiency&#xD;
             disease, or organ transplantation.&#xD;
&#xD;
          7. Evidence of coagulation disorders (INR&gt;1.5, APTT&gt;1.5 ULN), bleeding tendency(INR&#xD;
             should be in normal value without anticoagulation 14 days before randomization), usage&#xD;
             of anticoagulation or Vit K antagonist including warfarin, heparin or any other&#xD;
             analogue. When INR≤ 1.5, small dosage of warfarin(1 mg p.o, qd) or Aspirin (dosage &lt;&#xD;
             100mg/d) in preventive purpose is allowed.&#xD;
&#xD;
          8. Evidence of arterial/venous thrombotic events within 1 year before inclusion,&#xD;
             including cerebrovascular accident (including TIA), deep vein thrombosis( vein&#xD;
             thrombosis caused by venous catheterization in previous chemotherapy is excluded) and&#xD;
             pulmonary embolism.&#xD;
&#xD;
          9. Known severe hypersensitivity to Apatinib or any of the excipients of this product&#xD;
&#xD;
         10. Severe systemic disease out of control such as unstable or uncompensated&#xD;
             respiratory,cardiac,liver,renal diseases.&#xD;
&#xD;
         11. CNS metastases without radiotherapy and/or surgery. Patients with treated CNS&#xD;
             metastases may participate in this trial,except for those who must receive hormone&#xD;
             therapy and those whose prior hormone therapy for CNS metastases is less than 4 weeks.&#xD;
&#xD;
         12. psychiatric illness that would prevent the patient from giving informed consent&#xD;
&#xD;
         13. Patient has a concurrent malignancy or has a malignancy within 5 years of study&#xD;
             enrollment, with the exception of nonmelanoma skin cancer or cervical carcinoma in&#xD;
             situ&#xD;
&#xD;
         14. Patient is concurrently using other approved or investigational antineoplastic agent&#xD;
&#xD;
         15. Pregnant or lactating women&#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>Li Yuhong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>February 14, 2023</last_update_submitted>
  <last_update_submitted_qc>February 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Yuhong Li</investigator_full_name>
    <investigator_title>Clinical Professor</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>Apatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT02976896
org study id: Poetry-1
nct id: NCT02976896
lead sponsor: 
has dmc: Yes
We conduct the phase II clinical trial to further explore the efficacy and safety of Apatinib
      Mesylate in treating recurrent or metastatic esophageal squamous cell carcinoma after the
      failure of conventional treatments. An exploratory molecular marker analysis will be
      performed in order to find out the beneficial population of Apatinib Mesylate.
Esophageal cancer is one of the most common malignant tumor in China. In Asian countries,
      esophageal squamous cell carcinoma is the main pathological type of esophageal carcinoma.
      Prognosis of esophageal squamous cell carcinoma is usually poor and surgery is the only
      radical treatment. Cisplatin (DDP, cisplatin), 5 - Fluorouracil (5 - Fluorouracil, 5 - FU)
      and taxane are the most adopted chemotherapy agents, with efficacy rates of 33%-40% as
      first-line treatment for metastatic or recurrent esophageal squamous carcinoma and a median
      overall survival of 6-10 months. New agents were needed. Apatinib Mesylate is a small
      molecule VEGFR tyrosine kinase inhibitor. The anti-tumor mechanism of Apatinib is inhibiting
      angiogenesis in malignancy by inhibiting VEGFR. Apatinib Mesylate was approved by CFDA (China
      Food and Drug Administration) for the treatment of advanced gastric cancer. In the previous
      clinical practice, we observed that part of the patients with esophageal squamous cell
      carcinoma were resistant to conventional treatments benefited from Apatinib Mesylate. Based
      on the research situation mentioned above, we decided to conduct a phase II clinical trial to
      further explore the efficacy and safety of Apatinib Mesylate in treating recurrent or
      metastatic esophageal squamous cell carcinoma after the failure of conventional treatments.
      An exploratory molecular marker analysis will be performed in order to find out the
      beneficial population of Apatinib Mesylate.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease control rate
time frame: 6 months
measure: Overall survival
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Time to progression
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Incidence of Treatment-Emergent Adverse Events
time frame: Each follow up vist, assessed up to 12 months
description: Safety evaluation according to the CTCAE4.0 standard, once every 1 cycle assessment
measure: Quality of life using EORTC QLQ C30 - scale
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
description: Life quality evaluation using EORTC QLQ C30 - scale，once every 1 cycle assessment
measure: Quality of life using esophageal special scale QLQ - OES18
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
description: Life quality evaluation using esophageal special scale QLQ - OES18, once every 1 cycle assessment
arm group label: Apatinib Mesylate
arm group type: Experimental
description: Patients will receive Apatinib Mesylate at 500mg/times,oral one times daily for 28 days.
intervention type: Drug
intervention name: Apatinib Mesylate
description: Patients will receive Apatinib Mesylate at 500mg/times,oral one times daily for 28 days.
arm group label: Apatinib Mesylate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Li Yuhong, MD
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Yuhong Li
investigator title: Clinical Professor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Apatinib
sharing ipd: Yes