<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/NCT04481100</url>
  </required_header>
  <id_info>
    <org_study_id>20200707</org_study_id>
    <nct_id>NCT04481100</nct_id>
  </id_info>
  <brief_title>CCRT With Itraconazole in Locally Advanced Squamous Esophageal Cancer</brief_title>
  <official_title>Phase II Study of Concurrent Chemoradiotherapy With Itraconazole in Treating Patients With Locally Advanced Esophageal Squamous Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hangzhou Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hangzhou Cancer Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to evaluate the efficacy and safety of concurrent&#xD;
      chemoradiotherapy combined with Itraconazole in patients with locally adcvanced esophageal&#xD;
      squamous cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Esophageal cancer is one of the most lethal malignancies. Esophageal squamous cell carcinoma&#xD;
      (ESCC) is the predominant type in China, accounting for over 90% of all esophageal cancer.&#xD;
      Concurrent chemoradiation therapy (CCRT) remains the standard therapy of locally advanced&#xD;
      ESCC. However, the outcome remains poor.&#xD;
&#xD;
      The aberrant activation of Hedgehog (HH) signaling is associated with a variety of human&#xD;
      malignancies. Previous studies found that the reactivation of HH pathway occurs in 60% of&#xD;
      esophageal cancer. Targeting the Hh pathway for cancer therapy was expected to work wonders&#xD;
      in Hh-dependent cancers. Itraconazole, an antifungal agent, has been shown to inhibit the Hh&#xD;
      and AKT signaling pathways.&#xD;
&#xD;
      The aim of our study is to evaluate the efficacy and safety of concurrent chemoradiotherapy&#xD;
      combined with Itraconazole in patients with locally adcvanced esophageal squamous cancer&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 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>Objective response rate (ORR)</measure>
    <time_frame>4-8 weeks</time_frame>
    <description>ORR was evaluated 4-8 weeks after completion of RT and was recorded according to RECIST, version 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent adverse events</measure>
    <time_frame>year 0 - year 1</time_frame>
    <description>Incidence of treatment-emergent adverse events would be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAE v4.0) and EORTC criterion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local-regional free survival (LRFS)</measure>
    <time_frame>year 0 - year 3</time_frame>
    <description>LRFS was calculated from the date of treatment initiation to the date of documented failure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>year 0 - year 3</time_frame>
    <description>OS was determined as the time (in months) between the first day of therapy and the last follow-up or the date of death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">38</enrollment>
  <condition>Esophageal Neoplasm</condition>
  <condition>Esophageal Diseases</condition>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Itraconazole capsule 100mg twice daily for 6 weeks concurrent with chemoradation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>itraconazole</intervention_name>
    <description>Oral administration of itraconazole twice daily concurrent with chemoradiation</description>
    <arm_group_label>Experimental Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        age:18-75 years, male or femal.&#xD;
&#xD;
        Histologically or cytologically confirmed Squamous Cell Carcinoma of the Esophagus, locally&#xD;
        advanced, unresectable disease.&#xD;
&#xD;
        Clinical staged T3-4N0M0, T1-4N+M0,Ⅱ-Ⅳa(AJCC 8th)&#xD;
&#xD;
        Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.&#xD;
&#xD;
        ECOG 0-1.&#xD;
&#xD;
        Adequate organ function.&#xD;
&#xD;
        Patient has given written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Unwilling or unable to provide informed consent&#xD;
&#xD;
        Known allergy to itraconazole&#xD;
&#xD;
        Patients who have or are currently undergoing additional chemotherapy, radiation therapy,&#xD;
        targeted therapy or immunotherapy.&#xD;
&#xD;
        Complete obstruction of the esophagus, or patients who have the potential to develop&#xD;
        perforation, or unable to swallow Itraconazole.&#xD;
&#xD;
        Other malignancy within 5 years prior to entry into the study, expect for curatively&#xD;
        treated basal cell and squamous cell carcinoma of the skin and/or curatively resected&#xD;
        in-situ cervical and/or breast cancers.&#xD;
&#xD;
        Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small&#xD;
        molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or not recovered&#xD;
        from adverse events due to a previously administered agent.&#xD;
&#xD;
        Pregnancy or breast-feeding.&#xD;
&#xD;
        Decision of unsuitableness by principal investigator or physician-in-charge.&#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>Shixiu Wu, phD</last_name>
    <phone>86-755-66618168</phone>
    <email>wushixiu@medmail.com.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital &amp; Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518116</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shixiu Wu, phD</last_name>
      <phone>+8675566618168</phone>
      <email>wushixiu@medmail.com.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>October 13, 2020</last_update_submitted>
  <last_update_submitted_qc>October 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Shixiu Wu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Esophageal Squamous Cell Carcinoma</keyword>
  <keyword>Concurrent chemoradiotherapy</keyword>
  <keyword>Itraconazole</keyword>
  <keyword>Hedgehog pathway</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Esophageal Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04481100
org study id: 20200707
nct id: NCT04481100
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The objective of this study is to evaluate the efficacy and safety of concurrent
      chemoradiotherapy combined with Itraconazole in patients with locally adcvanced esophageal
      squamous cancer
Esophageal cancer is one of the most lethal malignancies. Esophageal squamous cell carcinoma
      (ESCC) is the predominant type in China, accounting for over 90% of all esophageal cancer.
      Concurrent chemoradiation therapy (CCRT) remains the standard therapy of locally advanced
      ESCC. However, the outcome remains poor.

      The aberrant activation of Hedgehog (HH) signaling is associated with a variety of human
      malignancies. Previous studies found that the reactivation of HH pathway occurs in 60% of
      esophageal cancer. Targeting the Hh pathway for cancer therapy was expected to work wonders
      in Hh-dependent cancers. Itraconazole, an antifungal agent, has been shown to inhibit the Hh
      and AKT signaling pathways.

      The aim of our study is to evaluate the efficacy and safety of concurrent chemoradiotherapy
      combined with Itraconazole in patients with locally adcvanced esophageal squamous cancer
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: 4-8 weeks
description: ORR was evaluated 4-8 weeks after completion of RT and was recorded according to RECIST, version 1.1
measure: Treatment-emergent adverse events
time frame: year 0 - year 1
description: Incidence of treatment-emergent adverse events would be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAE v4.0) and EORTC criterion.
measure: Local-regional free survival (LRFS)
time frame: year 0 - year 3
description: LRFS was calculated from the date of treatment initiation to the date of documented failure.
measure: Overall survival (OS)
time frame: year 0 - year 3
description: OS was determined as the time (in months) between the first day of therapy and the last follow-up or the date of death.
arm group label: Experimental Group
arm group type: Experimental
description: Itraconazole capsule 100mg twice daily for 6 weeks concurrent with chemoradation.
intervention type: Drug
intervention name: itraconazole
description: Oral administration of itraconazole twice daily concurrent with chemoradiation
arm group label: Experimental Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Shixiu Wu, phD
phone: 86-755-66618168
email: wushixiu@medmail.com.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Shixiu Wu
investigator title: Professor
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Esophageal Neoplasms
mesh term: Esophageal Diseases
mesh term: Itraconazole
sharing ipd: No