<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/NCT03251417</url>
  </required_header>
  <id_info>
    <org_study_id>AHEAD-HBE002</org_study_id>
    <nct_id>NCT03251417</nct_id>
  </id_info>
  <brief_title>Apatinib and Irinotecan Combination Treatment in Unresectable or Metastatic Esophageal Squamous Cell Carcinoma</brief_title>
  <official_title>Apatinib and Irinotecan Combination Treatment in Unresectable or Metastatic Esophageal Squamous Cell Carcinoma Patients Failed in First-line Chemotherapy: A Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Peking University Cancer Hospital &amp; Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking 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>
      Esophageal cancer is a common malignant disease worldwide especially in china. Though&#xD;
      esophagectomy and definitive chemoradiotherapy are standard treatments, disease relapses in&#xD;
      many patients and the prognosis of metastatic ESCC is still poor. For patients with&#xD;
      unresectable or metastatic ESCC, chemotherapy is an important treatment alone or with&#xD;
      radiotherapy. Taxane, platinum, and fluoropyrimidine have been reported effective in ESCC and&#xD;
      is used as first-line treatment of ESCC. As for 2nd-line treatment, both irinotecan and&#xD;
      taxane had been recommended based on data from clinical trials which were most enrolled&#xD;
      esophageal or esophageal-gastric junction adenocarcinoma and with only small sample size.&#xD;
      Therefore, it is still urgently needed to explore effective 2nd-line treatment for ESCC.&#xD;
&#xD;
      Apatinib, also known as YN968D1, is an orally antiangiogenic agents. Preclinical and clinical&#xD;
      data had shown that it is effective in the treatment of a variety of solid tumors including&#xD;
      esophageal cancer. It had been approved as a 3rd-line treatment for patients with advanced&#xD;
      gastric cancer by state FDA of China in 2014. And the safety data showed that hemorrhage is&#xD;
      rare and non-fetal which is different from bevacizumab.&#xD;
&#xD;
      Therefore, the investigators initialize this phase II study to explore the efficacy and&#xD;
      safety of irinotecan and apatinib combination treatment in unresectable or metastatic ESCC&#xD;
      patients who failed in 1st-line chemotherapy or chemoradiotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Because PD-1 antibodies had been proved to be a standard second-line treatment in esophageal&#xD;
    cancer, the potential benefit of present intervention is under re-evaluation.&#xD;
  </why_stopped>
  <start_date type="Actual">September 10, 2017</start_date>
  <completion_date type="Actual">April 25, 2021</completion_date>
  <primary_completion_date type="Actual">April 25, 2021</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>From enrollment to 3 months after treatment.</time_frame>
    <description>The percentage of patients with CR, PR, and SD response after 3 cycles' treatment according to RESIST v1.1 criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety: All reported adverse events (NCI CTCAE 4.0 criteria)</measure>
    <time_frame>From enrollment to progression of disease or 1 months after treatment.</time_frame>
    <description>All reported adverse events (NCI CTCAE 4.0 criteria) during treatment and one months after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>From enrollment to 3 months after treatment</time_frame>
    <description>Clinical response rate of treatment (CR+PR) according to RESIST v1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median progression-free survival time</measure>
    <time_frame>From enrollment to progression of disease. Estimated time is about 4 months</time_frame>
    <description>The length of time from enrollment until the time of progression of disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median overall survival time</measure>
    <time_frame>From enrollment to death of patients, estimated about 8 months.</time_frame>
    <description>The length of time from enrollment until the time of death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Combination treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination treatment of irinotecan and apatinib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>Irinotecan 150mg/m2, repeated very 2 weeks for 3 to 6 cycles.</description>
    <arm_group_label>Combination treatment</arm_group_label>
    <other_name>CPT-11</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib 500 mg oral take, daily</description>
    <arm_group_label>Combination treatment</arm_group_label>
    <other_name>YN968D1</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 to 70 years. Both genders are eligible.&#xD;
&#xD;
          -  Patients must have histologically confirmed esophageal squamous cell carcinoma with&#xD;
             unresectable or metastatic disease.&#xD;
&#xD;
          -  With measurable or evaluable disease defined by RECIST 1.1 criteria by multi-slice&#xD;
             spiral CT or MR scan.&#xD;
&#xD;
          -  Failed in or disease progressed after fist-line chemotherapy (A. If failed in&#xD;
             preoperative chemotherapy / chemoradiotherapy or disease progressed in 24 weeks after&#xD;
             esophagectomy, the preoperative chemotherapy/ chemoradiotherapy is regard as&#xD;
             first-line chemotherapy. B. If failed in definitive chemoradiotherapy or disease&#xD;
             progressed in 24 weeks after definitive chemoradiotherapy, the definitive&#xD;
             chemoradiotherapy is regard as first-line chemotherapy; C. If failed in or relapse in&#xD;
             24 weeks after adjuvant chemotherapy, the adjuvant chemotherapy is regard as first&#xD;
             line chemotherapy).&#xD;
&#xD;
          -  Patients must have a performance status of 0-2 on the ECOG scale.&#xD;
&#xD;
          -  Life expectancy ≥3 months.&#xD;
&#xD;
          -  With normal marrow, liver and renal function:a hemoglobin (HGB) of ≥110g/L (without&#xD;
             blood transfusion during 14 days); a neutrophil count of ≥2.0×109/L; a platelet count&#xD;
             of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL) or ≤3&#xD;
             UNL in case of liver metastasis. a creatinine (Cr) of ≤ 1.5 UNL or a creatinine&#xD;
             clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and&#xD;
             aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis.&#xD;
             Fecal occult blood (-); Urine test: protein&lt;(++) or &lt;1.0g per 24 hours.&#xD;
&#xD;
          -  Without bleeding and thrombosis disease.&#xD;
&#xD;
          -  With normal coagulation function: APTT, PT and INR, each ≤ 1.5 ULN&#xD;
&#xD;
          -  With normal electrocardiogram results and no history of congestive heart failure.&#xD;
&#xD;
          -  Female subjects of child-bearing potential must agree to use contraceptive measures&#xD;
             starting 1 week before the administration of the first dose of apatinib until 8 weeks&#xD;
             after discontinuing study drug. Male subjects must agree to use contraceptive measures&#xD;
             during the study and 8 weeks after last dose of study drug.&#xD;
&#xD;
          -  With good compliance and agree to accept follow-up of disease progression and adverse&#xD;
             events.&#xD;
&#xD;
          -  With written informed consent signed voluntarily by patients themselves or their&#xD;
             supervisors witted by doctors.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received irinotecan or apatinib in previous treatment.&#xD;
&#xD;
          -  Other pathological type cancers of esophagus except for squamous cell carcinoma&#xD;
&#xD;
          -  Uncontrolled hypertension (Treatment of antihypertensive drugs cannot reduced to the&#xD;
             normal range: systolic pressure ≤140 mmHg and diastolic pressure ≤90 mmHg)&#xD;
&#xD;
          -  With ≥grade 2 coronary heart disease, arrhythmia (including QTc interval prolongation&#xD;
             male &gt;450 ms, women &gt;470 ms)&#xD;
&#xD;
          -  Cannot take oral tables including uncontrolled vomiting, chronic diarrhea and&#xD;
             intestinal obstruction.&#xD;
&#xD;
          -  With potential bleeding risk of GI including (1) peptic ulcer and fecal occult blood&#xD;
             (++ - +++); (2) melena or hematemesis history in last 3 months;(3) In case of fecal&#xD;
             occult blood (+) or (+/-),fecal occult blood examination must be repeat in one week.&#xD;
             If fecal occult blood is still (+) or (+/-),endoscopy is required and if there are&#xD;
             ulcer or other diseases with bleeding risk in the opinion of the investigators. (4)&#xD;
             Primary tumour lesion is of deep ulcer and in the opinion of the investigators may&#xD;
             place the patient at risk of fetal bleeding or GI perforation.&#xD;
&#xD;
          -  Urine test: protein&gt;(++) or &gt;1.0g per 24 hours.&#xD;
&#xD;
          -  With abnormal coagulation function (INR&gt;1.5 ULN, APTT&gt;1.5 ULN),&#xD;
&#xD;
          -  With thrombosis or receiving anticoagulant treatment.&#xD;
&#xD;
          -  With serious diseases such as congestive heart failure, uncontrolled myocardial&#xD;
             infarction and arrhythmia, liver failure and renal failure.&#xD;
&#xD;
          -  With brain metastasis&#xD;
&#xD;
          -  Pregnant or lactated women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jun Jia, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing Cancer Hospital/ Peking University Cancer Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Cancer Hospital / Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>January 30, 2023</last_update_submitted>
  <last_update_submitted_qc>January 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University Cancer Hospital &amp; Institute</investigator_affiliation>
    <investigator_full_name>Xiaodong Zhang</investigator_full_name>
    <investigator_title>Associated Professor of the VIP2 GI Division of Medical Department</investigator_title>
  </responsible_party>
  <keyword>Irinotecan</keyword>
  <keyword>Apatinib</keyword>
  <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>Irinotecan</mesh_term>
    <mesh_term>Apatinib</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/NCT03251417
org study id: AHEAD-HBE002
nct id: NCT03251417
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Esophageal cancer is a common malignant disease worldwide especially in china. Though
      esophagectomy and definitive chemoradiotherapy are standard treatments, disease relapses in
      many patients and the prognosis of metastatic ESCC is still poor. For patients with
      unresectable or metastatic ESCC, chemotherapy is an important treatment alone or with
      radiotherapy. Taxane, platinum, and fluoropyrimidine have been reported effective in ESCC and
      is used as first-line treatment of ESCC. As for 2nd-line treatment, both irinotecan and
      taxane had been recommended based on data from clinical trials which were most enrolled
      esophageal or esophageal-gastric junction adenocarcinoma and with only small sample size.
      Therefore, it is still urgently needed to explore effective 2nd-line treatment for ESCC.

      Apatinib, also known as YN968D1, is an orally antiangiogenic agents. Preclinical and clinical
      data had shown that it is effective in the treatment of a variety of solid tumors including
      esophageal cancer. It had been approved as a 3rd-line treatment for patients with advanced
      gastric cancer by state FDA of China in 2014. And the safety data showed that hemorrhage is
      rare and non-fetal which is different from bevacizumab.

      Therefore, the investigators initialize this phase II study to explore the efficacy and
      safety of irinotecan and apatinib combination treatment in unresectable or metastatic ESCC
      patients who failed in 1st-line chemotherapy or chemoradiotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease control rate
time frame: From enrollment to 3 months after treatment.
description: The percentage of patients with CR, PR, and SD response after 3 cycles' treatment according to RESIST v1.1 criteria.
measure: Safety: All reported adverse events (NCI CTCAE 4.0 criteria)
time frame: From enrollment to progression of disease or 1 months after treatment.
description: All reported adverse events (NCI CTCAE 4.0 criteria) during treatment and one months after treatment.
measure: Objective response rate
time frame: From enrollment to 3 months after treatment
description: Clinical response rate of treatment (CR+PR) according to RESIST v1.1 criteria
measure: Median progression-free survival time
time frame: From enrollment to progression of disease. Estimated time is about 4 months
description: The length of time from enrollment until the time of progression of disease
measure: Median overall survival time
time frame: From enrollment to death of patients, estimated about 8 months.
description: The length of time from enrollment until the time of death.
arm group label: Combination treatment
arm group type: Experimental
description: Combination treatment of irinotecan and apatinib.
intervention type: Drug
intervention name: Irinotecan
description: Irinotecan 150mg/m2, repeated very 2 weeks for 3 to 6 cycles.
arm group label: Combination treatment
other name: CPT-11
intervention type: Drug
intervention name: Apatinib
description: Apatinib 500 mg oral take, daily
arm group label: Combination treatment
other name: YN968D1
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jun Jia, M.D.
role: Principal Investigator
affiliation: Beijing Cancer Hospital/ Peking University Cancer Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University Cancer Hospital & Institute
investigator full name: Xiaodong Zhang
investigator title: Associated Professor of the VIP2 GI Division of Medical Department
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Irinotecan
mesh term: Apatinib
sharing ipd: Undecided