<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/NCT03267173</url>
  </required_header>
  <id_info>
    <org_study_id>Yunwei Wei</org_study_id>
    <nct_id>NCT03267173</nct_id>
  </id_info>
  <brief_title>Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer.</brief_title>
  <official_title>Evaluate the Safety and Efficacy of Chimeric Antigen Receptor Engineered T Cell Immunotherapy (CAR-T) in the Treatment of Pancreatic Cancer in a Single Center, Non Controlled Clinical Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital of Harbin Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>First Affiliated Hospital of Harbin Medical University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Immunotherapy has become the major breakthrough and the most promising treatment, with the&#xD;
      host of development of tumor biology, molecular biology and immunology. It has become the&#xD;
      fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy,&#xD;
      radiotherapy) . Mesothelin, PSCA, CEA, HER2, MUC1 and EGFRvIII are potential targets and&#xD;
      spectacular paradigm in the diagnosis and treatment of pancreatic cancer. This study is for&#xD;
      evaluation of the safety and efficacy of Mesothelin, PSCA, CEA, HER2, MUC1, EGFRvIII targeted&#xD;
      and other CAR-T cell immunotherapy for pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immunotherapy has become the major breakthrough and the most promising treatment, with the&#xD;
      host of development of tumor biology, molecular biology and immunology. It has become the&#xD;
      fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy,&#xD;
      radiotherapy) . With the development of the research field, the CAR-T cell basis and clinical&#xD;
      research of various targets have achieved good results. Mesothelin, PSCA, CEA, HER2, MUC1 and&#xD;
      EGFRvIII are potential targets and spectacular paradigm in the diagnosis and treatment of&#xD;
      pancreatic cancer. This study is for evaluation of the safety and efficacy of Mesothelin,&#xD;
      PSCA, CEA, HER2, MUC1, EGFRvIII targeted and other CAR-T cell immunotherapy for pancreatic&#xD;
      cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 15, 2017</start_date>
  <completion_date type="Anticipated">June 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</primary_completion_date>
  <phase>Early Phase 1</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>Number of patients with tumor response</measure>
    <time_frame>8 weeks</time_frame>
    <description>Tumor response is assessmented with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse event</measure>
    <time_frame>8 weeks</time_frame>
    <description>Asverse event is evaluated with CTCAE, version 4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Pancreatic Cancer</condition>
  <condition>CAR</condition>
  <arm_group>
    <arm_group_label>CAR-T</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of Chimeric antigen receptor T cells will be administered by vascular interventional mediated as one dose infusions. According to the patient's condition and weight, the intervention dose of aE7 CAR-T cells per kilogram of body weight was treated once.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chimeric antigen receptor T cell</intervention_name>
    <description>Evaluate the efficacy and safety of targeted Mesothelin/PSCA/CEA/HER2/MUC1/, EGFRvIII and other chimeric antigen receptor engineered T cell immunotherapy in the treatment of pancreatic cancer.</description>
    <arm_group_label>CAR-T</arm_group_label>
    <other_name>meso-CAR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Imaging, pathology or biopsy confirmed as pancreatic cancer and it has metastasized,&#xD;
             can not radical cured by surgery; patients restored good but there is still residual&#xD;
             lesions, recurrence or metastasis 1 months after surgery;&#xD;
&#xD;
          -  Accepted more than 1 times chemotherapy which is invalid or unwilling to accept&#xD;
             previous chemotherapy patients;&#xD;
&#xD;
          -  The corresponding antigens such as Meso and PSCA/ CEA/ HER2/ MUC1/ EGFRvIII were&#xD;
             highly expressed;&#xD;
&#xD;
          -  Male patients aged between 18 and 65;&#xD;
&#xD;
          -  Life expectancy greater than 1 months;&#xD;
&#xD;
          -  Karnofsky score ≥ 60, ECOG≤ 2;&#xD;
&#xD;
          -  Important organ function as defined by the following: cardiac ejection fraction ≥ 50%;&#xD;
             electrocardiogram showed no obvious abnormalities; creatinine clearance rate&#xD;
             calculated by using Cockcroft- Gault formula ≥40ml/min ; ALT/AST≤ 3×the institution&#xD;
             normal upper limit; total bilirubin ≤2.0mg/dl; coagulation function: PT/ APPT&lt;2 ×the&#xD;
             institution normal upper limit; SpO2 &gt;92%; Blood: hemoglobin&gt;80g/L, ANC ≥ 1, PLT ≥&#xD;
             50×109/L;&#xD;
&#xD;
          -  There is measurable target lesion;&#xD;
&#xD;
          -  Voluntary informed consent is given.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Immunosuppressive drugs or hormones were used a week before admission;&#xD;
&#xD;
          -  Severe active infection;&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) positive;&#xD;
&#xD;
          -  Active hepatitis B or C infection;&#xD;
&#xD;
          -  Past medical history of other malignancies. Not included: patients who have been cured&#xD;
             at any time prior to the treatment of the skin basal or squamous cell carcinoma and&#xD;
             cervical carcinoma in situ; the other tumor has not listed above, but has been used&#xD;
             and only cured by surgery, without further treatment by other measures, the subjects&#xD;
             of disease-free survival more than 5 years, can be included in the study;&#xD;
&#xD;
          -  Patients participating in other clinical trials;&#xD;
&#xD;
          -  The researchers thought the subjects were unfit for inclusion or unable to participate&#xD;
             in or complete the study；&#xD;
&#xD;
          -  Patients with congenital immunodeficiency；&#xD;
&#xD;
          -  There is a history of myocardial infarction and serious arrhythmia within six months.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei Yunwei, Dctor</last_name>
    <role>Study Director</role>
    <affiliation>First Affiliated Hospital of Harbin Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wei Yunwei, Dctor</last_name>
    <phone>86-85553099</phone>
    <email>hydwyw11@hotmall.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhao Lei, Dctor</last_name>
    <phone>86-13069890888</phone>
    <email>zhaoleihyd@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Harbin Medical University</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <zip>150001</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhao Lei, Doctor</last_name>
      <phone>86-13069890888</phone>
      <email>zhaoleihyd@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://www.ncbi.nlm.nih.gov</url>
    <description>References are all derived from PubMed</description>
  </link>
  <reference>
    <citation>Zervos E, Agle S, Freistaedter AG, Jones GJ, Roper RL. Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer. J Exp Clin Cancer Res. 2016 Mar 1;35:39. doi: 10.1186/s13046-016-0314-2.</citation>
    <PMID>26931187</PMID>
  </reference>
  <reference>
    <citation>Freedman JD, Hagel J, Scott EM, Psallidas I, Gupta A, Spiers L, Miller P, Kanellakis N, Ashfield R, Fisher KD, Duffy MR, Seymour LW. Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies. EMBO Mol Med. 2017 Aug;9(8):1067-1087. doi: 10.15252/emmm.201707567.</citation>
    <PMID>28634161</PMID>
  </reference>
  <reference>
    <citation>Morello A, Sadelain M, Adusumilli PS. Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors. Cancer Discov. 2016 Feb;6(2):133-46. doi: 10.1158/2159-8290.CD-15-0583. Epub 2015 Oct 26.</citation>
    <PMID>26503962</PMID>
  </reference>
  <reference>
    <citation>Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, Morse M, Zeh H, Cohen D, Fine RL, Onners B, Uram JN, Laheru DA, Lutz ER, Solt S, Murphy AL, Skoble J, Lemmens E, Grous J, Dubensky T Jr, Brockstedt DG, Jaffee EM. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015 Apr 20;33(12):1325-33. doi: 10.1200/JCO.2014.57.4244. Epub 2015 Jan 12.</citation>
    <PMID>25584002</PMID>
  </reference>
  <reference>
    <citation>Abate-Daga D, Lagisetty KH, Tran E, Zheng Z, Gattinoni L, Yu Z, Burns WR, Miermont AM, Teper Y, Rudloff U, Restifo NP, Feldman SA, Rosenberg SA, Morgan RA. A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther. 2014 Dec;25(12):1003-12. doi: 10.1089/hum.2013.209.</citation>
    <PMID>24694017</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>August 27, 2017</last_update_submitted>
  <last_update_submitted_qc>August 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pancreatic Cancer</keyword>
  <keyword>CAR-T</keyword>
  <keyword>Mesothelin</keyword>
  <keyword>CEA</keyword>
  <keyword>HER2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_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/NCT03267173
org study id: Yunwei Wei
nct id: NCT03267173
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Immunotherapy has become the major breakthrough and the most promising treatment, with the
      host of development of tumor biology, molecular biology and immunology. It has become the
      fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy,
      radiotherapy) . Mesothelin, PSCA, CEA, HER2, MUC1 and EGFRvIII are potential targets and
      spectacular paradigm in the diagnosis and treatment of pancreatic cancer. This study is for
      evaluation of the safety and efficacy of Mesothelin, PSCA, CEA, HER2, MUC1, EGFRvIII targeted
      and other CAR-T cell immunotherapy for pancreatic cancer.
Immunotherapy has become the major breakthrough and the most promising treatment, with the
      host of development of tumor biology, molecular biology and immunology. It has become the
      fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy,
      radiotherapy) . With the development of the research field, the CAR-T cell basis and clinical
      research of various targets have achieved good results. Mesothelin, PSCA, CEA, HER2, MUC1 and
      EGFRvIII are potential targets and spectacular paradigm in the diagnosis and treatment of
      pancreatic cancer. This study is for evaluation of the safety and efficacy of Mesothelin,
      PSCA, CEA, HER2, MUC1, EGFRvIII targeted and other CAR-T cell immunotherapy for pancreatic
      cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with tumor response
time frame: 8 weeks
description: Tumor response is assessmented with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
measure: Number of patients with adverse event
time frame: 8 weeks
description: Asverse event is evaluated with CTCAE, version 4.0
arm group label: CAR-T
arm group type: Experimental
description: A single dose of Chimeric antigen receptor T cells will be administered by vascular interventional mediated as one dose infusions. According to the patient's condition and weight, the intervention dose of aE7 CAR-T cells per kilogram of body weight was treated once.
intervention type: Drug
intervention name: Chimeric antigen receptor T cell
description: Evaluate the efficacy and safety of targeted Mesothelin/PSCA/CEA/HER2/MUC1/, EGFRvIII and other chimeric antigen receptor engineered T cell immunotherapy in the treatment of pancreatic cancer.
arm group label: CAR-T
other name: meso-CAR
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Wei Yunwei, Dctor
role: Study Director
affiliation: First Affiliated Hospital of Harbin Medical University
last name: Wei Yunwei, Dctor
phone: 86-85553099
email: hydwyw11@hotmall.com
last name: Zhao Lei, Dctor
phone: 86-13069890888
email: zhaoleihyd@163.com
facility: 
status: Recruiting
contact: 
country: China
url: http://www.ncbi.nlm.nih.gov
description: References are all derived from PubMed
citation: Zervos E, Agle S, Freistaedter AG, Jones GJ, Roper RL. Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer. J Exp Clin Cancer Res. 2016 Mar 1;35:39. doi: 10.1186/s13046-016-0314-2.
PMID: 26931187
citation: Freedman JD, Hagel J, Scott EM, Psallidas I, Gupta A, Spiers L, Miller P, Kanellakis N, Ashfield R, Fisher KD, Duffy MR, Seymour LW. Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies. EMBO Mol Med. 2017 Aug;9(8):1067-1087. doi: 10.15252/emmm.201707567.
PMID: 28634161
citation: Morello A, Sadelain M, Adusumilli PS. Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors. Cancer Discov. 2016 Feb;6(2):133-46. doi: 10.1158/2159-8290.CD-15-0583. Epub 2015 Oct 26.
PMID: 26503962
citation: Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, Morse M, Zeh H, Cohen D, Fine RL, Onners B, Uram JN, Laheru DA, Lutz ER, Solt S, Murphy AL, Skoble J, Lemmens E, Grous J, Dubensky T Jr, Brockstedt DG, Jaffee EM. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015 Apr 20;33(12):1325-33. doi: 10.1200/JCO.2014.57.4244. Epub 2015 Jan 12.
PMID: 25584002
citation: Abate-Daga D, Lagisetty KH, Tran E, Zheng Z, Gattinoni L, Yu Z, Burns WR, Miermont AM, Teper Y, Rudloff U, Restifo NP, Feldman SA, Rosenberg SA, Morgan RA. A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther. 2014 Dec;25(12):1003-12. doi: 10.1089/hum.2013.209.
PMID: 24694017
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
sharing ipd: No