<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/NCT03833466</url>
  </required_header>
  <id_info>
    <org_study_id>ESCC-MTPneo</org_study_id>
    <nct_id>NCT03833466</nct_id>
  </id_info>
  <brief_title>Metformin in Combined With Cisplatin Plus Paclitaxel With Advanced Esophageal Squamous Cell Carcinoma (ECMTPneo)</brief_title>
  <acronym>ECMTPneo</acronym>
  <official_title>Metformin in Combined With Cisplatin Plus Paclitaxel as Neoadjuvant Therapy With Advanced Esophageal Squamous Cell Carcinoma (ESCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label phase II trial investigating the effect of metformin in combined with&#xD;
      cisplatin plus paclitaxel as neoadjuvant therapy with advanced esophageal squamous cell&#xD;
      carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this prospective phase II study, eligible patients are received cisplatin plus paclitaxel&#xD;
      for 2-4 cycles combined with metformin orally. The investigators aim to compare the tumor&#xD;
      metabolic pathway and tumor microenvironment of pre-chemotherapy endoscopic biopsy samples&#xD;
      and post-chemotherapy surgical resection samples.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 5, 2019</start_date>
  <completion_date type="Anticipated">June 20, 2020</completion_date>
  <primary_completion_date type="Anticipated">March 20, 2020</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>Tumor metabolic pathway</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>To compare the changes of tumor metabolic pathway of pre-chemotherapy endoscopic biopsy samples and post-chemotherapy surgical resection samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tumor microenvironment</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>To compare the changes of tumor microenvironment of pre-chemotherapy endoscopic biopsy samples and post-chemotherapy surgical resection samples</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of pathologic complete response（pCR）</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Rate of pathologic complete response</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>metformin and chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin and chemotherapy</intervention_name>
    <description>Drug: Metformin Metformin is orally administered as 500mg bid for 7 days and escaladed to 500mg tid if adverse events are tolerated.&#xD;
Drug: Cisplatin Cisplatin is given at 75mg/m2 intravenously on day 1 of each 21 day cycle.&#xD;
Drug: Paclitaxel Paclitaxel is given at 175mg/m2 intravenously on day 1 of each 21 day cycle.</description>
    <arm_group_label>metformin and chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Having signed informed consent.&#xD;
&#xD;
          -  Age 18 to 70 years old&#xD;
&#xD;
          -  Histologically confirmed esophageal squamous carcinoma&#xD;
&#xD;
          -  Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed advanced ESCC&#xD;
             which need neoadjuvant chemotherapy before surgical resection.&#xD;
&#xD;
          -  Measurable disease according to the Response Evaluation Criteria In Solid Tumors&#xD;
             (RECIST) 1.1 criteria(diameter of the lesion should be more than 10mm by spiral CT or&#xD;
             MRI, more than 20mm by common CT, the date of image should be less than 21 days before&#xD;
             enrollment)&#xD;
&#xD;
          -  Life expectancy of ≥3 month&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) 0-1&#xD;
&#xD;
          -  Body Mass Index (BMI) ≥18.5kg/m2&#xD;
&#xD;
          -  WBC&gt;3,000/mm3, absolute neutrophil count ≥1500/mm3, platelet&gt;100,000/mm3,&#xD;
             Hb&gt;9g/dl，Bilirubin level &lt; 1.5 times ULN，Serum creatinine &lt;1.5 times ULN，ALT and&#xD;
             AST&lt;2.5 times ULN ，AKP &lt; 2.5 times ULN ，(≤5 times ULN in patients with liver&#xD;
             metastases)(within 7 days before enrollment)&#xD;
&#xD;
          -  No sever complication, such as active gastrointestinal bleeding, perforation,&#xD;
             jaundice, obstruction, non-cancerous fever&gt;38℃.&#xD;
&#xD;
          -  Good compliance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have used metformin or biguanide in the past&#xD;
&#xD;
          -  Contraindications of metformin&#xD;
&#xD;
          -  Unable to take metformin orally because of esophageal stenosis&#xD;
&#xD;
          -  Currently receiving other effective regimens&#xD;
&#xD;
          -  Previous anticipate other clinical trial within 4 weeks before entering this study&#xD;
&#xD;
          -  No measurable lesions, eg. pleural fluid and ascites\&#xD;
&#xD;
          -  Only with other previous malignancy within 5 year, except non-melanoma skin cancer and&#xD;
             cervical carcinoma in situ&#xD;
&#xD;
          -  Heart failure or other sever organ dysfunction, eg. coronary artery disease,&#xD;
             myocardial infarction within the last 6 months only Brain or bone metastasis&#xD;
&#xD;
          -  Mentally abnormal or disable cognition,including central nervous system (CNS)&#xD;
             metastasis&#xD;
&#xD;
          -  HIV infection, active hepatitis B or hepatitis C&#xD;
&#xD;
          -  Unstable systemic diseases such as poorly controlled diabetes&#xD;
&#xD;
          -  Interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or&#xD;
             evidence of interstitial lung disease showed in X-ray/CT&#xD;
&#xD;
          -  Known hypersensitivity to study drugs&#xD;
&#xD;
          -  Pregnancy or lactation period&#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>Zhihao Lu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhihao Lu, MD</last_name>
    <phone>86-10-88196561</phone>
    <email>13810549767@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lin Shen, MD</last_name>
    <phone>86-10-88196561</phone>
    <email>linshenpku@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peking Universtiy 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>February 2019</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>February 13, 2019</last_update_submitted>
  <last_update_submitted_qc>February 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University</investigator_affiliation>
    <investigator_full_name>Shen Lin</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Advanced Esophageal Squamous Cell Carcinoma</keyword>
  <keyword>Neoadjuvant Therapy</keyword>
  <keyword>Metformin</keyword>
  <keyword>Cisplatin</keyword>
  <keyword>Paclitaxel</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>Metformin</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/NCT03833466
org study id: ESCC-MTPneo
nct id: NCT03833466
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is an open-label phase II trial investigating the effect of metformin in combined with
      cisplatin plus paclitaxel as neoadjuvant therapy with advanced esophageal squamous cell
      carcinoma.
In this prospective phase II study, eligible patients are received cisplatin plus paclitaxel
      for 2-4 cycles combined with metformin orally. The investigators aim to compare the tumor
      metabolic pathway and tumor microenvironment of pre-chemotherapy endoscopic biopsy samples
      and post-chemotherapy surgical resection samples.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Tumor metabolic pathway
time frame: Through study completion, an average of 1 year
description: To compare the changes of tumor metabolic pathway of pre-chemotherapy endoscopic biopsy samples and post-chemotherapy surgical resection samples
measure: Tumor microenvironment
time frame: Through study completion, an average of 1 year
description: To compare the changes of tumor microenvironment of pre-chemotherapy endoscopic biopsy samples and post-chemotherapy surgical resection samples
measure: Rate of pathologic complete response（pCR）
time frame: Through study completion, an average of 1 year
description: Rate of pathologic complete response
arm group label: metformin and chemotherapy
arm group type: Experimental
intervention type: Drug
intervention name: metformin and chemotherapy
description: Drug: Metformin Metformin is orally administered as 500mg bid for 7 days and escaladed to 500mg tid if adverse events are tolerated.
Drug: Cisplatin Cisplatin is given at 75mg/m2 intravenously on day 1 of each 21 day cycle.
Drug: Paclitaxel Paclitaxel is given at 175mg/m2 intravenously on day 1 of each 21 day cycle.
arm group label: metformin and chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Zhihao Lu, MD
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
last name: Zhihao Lu, MD
phone: 86-10-88196561
email: 13810549767@126.com
last name: Lin Shen, MD
phone: 86-10-88196561
email: linshenpku@163.com
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University
investigator full name: Shen Lin
investigator title: Clinical Professor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Metformin
sharing ipd: No