<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/NCT04430595</url>
  </required_header>
  <id_info>
    <org_study_id>GIMI-IRB-20005</org_study_id>
    <nct_id>NCT04430595</nct_id>
  </id_info>
  <brief_title>Multi-4SCAR-T Therapy Targeting Breast Cancer</brief_title>
  <official_title>Multiple 4SCAR-T Cell Therapy Targeting Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Geno-Immune Medical Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Seventh Affiliated Hospital of Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shenzhen Geno-Immune Medical Institute</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>
      The purpose of this study is to assess the feasibility, safety and efficacy of multiple 4th&#xD;
      generation CAR-T cells targeting Her2, GD2, and CD44v6 surface antigen in breast cancer.&#xD;
      Another goal of the study is to learn more about the activities of the multi-CAR T cells and&#xD;
      their persistency in the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Breast cancer is one of the most frequent cancer types in women. The average risk of a woman&#xD;
      in the United States developing breast cancer in her life is about 13%. That means that there&#xD;
      is a 1 in 8 chance she will develop breast cancer. Human epidermal growth factor receptor-2&#xD;
      (HER2) is one of the more well-researched genes in breast cancer so far. It has been reported&#xD;
      that HER2 gene is overexpressed in 20% to 30% of breast cancer patients. HER2 is an important&#xD;
      target for tumor gene therapy. In 2003, scientists confirmed the existence of breast cancer&#xD;
      stem cells. In 2012, ganglioside GD2 was confirmed as an emerging marker of breast cancer&#xD;
      stem cells. Targeting therapies for GD2 may help improve the survival rate and cure rate of&#xD;
      breast cancer patients. Invasion and metastasis of tumor cells is the main cause of cancer&#xD;
      death. CD44v6 is an adhesion molecule on the cell surface, which not only promotes&#xD;
      epithelial-mesenchymal transition, degradation and remodeling of extracellular matrix, but&#xD;
      also participates in organ-specific metastasis of tumor cells. Studies have shown that&#xD;
      overexpression of CD44v6 is an important factor for the invasion and metastasis of breast&#xD;
      cancer, and is closely related to the tumor size of the breast cancer, tumor staging, and&#xD;
      lymph node metastasis. Therefore, CD44v6 may be an important target for the treatment of&#xD;
      breast cancer. Using Her2-, GD2- and CD44v6-specific CAR-T cells may effectively improve the&#xD;
      immunotherapy treatment, prevent tumor cells from escaping treatment, and achieve the effect&#xD;
      of long-term disease relief.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">June 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2023</primary_completion_date>
  <phase>Phase 1/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>Number of patients with adverse events.</measure>
    <time_frame>3 year</time_frame>
    <description>Determine the toxicity profile the multi-4SCAR-T cells with Common Toxicity Criteria for Adverse Effects version 4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-tumor effects</measure>
    <time_frame>3 year</time_frame>
    <description>Disease status is defined by the image scan to get the outcomes such as Complete response/remission (CR), Very good partial response/remission (VGPR), etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The expansion and persistence of CAR-T cells</measure>
    <time_frame>3 months</time_frame>
    <description>The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival time of the patients</measure>
    <time_frame>3 year</time_frame>
    <description>The survival time of the patients treated with the multi-4SCAR T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Multiple 4SCAR T cells to treat breast cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple 4SCAR T cells to treat breast cancer</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4SCAR T cells</intervention_name>
    <description>Infusion of 4SCAR-GD2, -Her2 and -CD44v6 CAR-T cells</description>
    <arm_group_label>Multiple 4SCAR T cells to treat breast cancer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with stage III, IV or relapsed breast cancer confirmed by histology and&#xD;
             biopsy.&#xD;
&#xD;
          2. Age: ≥ 18 years and ≤ 75 years.&#xD;
&#xD;
          3. 2 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since&#xD;
             last systemic steroid hormone and other immunosuppressive therapy.&#xD;
&#xD;
          4. Side effects of chemotherapy have subsided.&#xD;
&#xD;
          5. The target antigens GD2, CD44v6, or Her2 is expressed in malignancy tissues by&#xD;
             immuno-histochemical or flow cytometry.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.&#xD;
&#xD;
          7. Expected survival ≥ 12 weeks.&#xD;
&#xD;
          8. Initial hematopoietic reconstitution with neutrophils (ANC) ≥ 1×10^6/L; platelet (PLT)&#xD;
             ≥ 1×10^8/L.&#xD;
&#xD;
          9. Proper renal and hepatic functions (ULN denotes &quot;upper limit of normal range&quot;) with&#xD;
             serum creatinine ≤ 2×ULN; serum bilirubin ≤ 3×ULN; AST/ALT ≤ 2.5×ULN.&#xD;
&#xD;
         10. Oxygen saturation ≥ 90%.&#xD;
&#xD;
         11. Written, informed consent obtained prior to any study-specific procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Airway obstruction caused by tumor.&#xD;
&#xD;
          2. History of epilepsy or other central nervous system diseases.&#xD;
&#xD;
          3. Patients who require systemic corticosteroid or other immunosuppressive therapy.&#xD;
&#xD;
          4. History of prolonged or serious heart disease during QT.&#xD;
&#xD;
          5. Current or recent treatment (within the 28-day period prior to Day 0) with another&#xD;
             investigational drug or previous participation in this study.&#xD;
&#xD;
          6. Inadequate liver and renal function with serum creatinine &gt; 1.5 mg/dl; serum (total)&#xD;
             bilirubin &gt; 2.0 mg/dl; AST &amp; ALT &gt; 3 x ULN.&#xD;
&#xD;
          7. Pregnant or lactating females.&#xD;
&#xD;
          8. Serious active infection during screening.&#xD;
&#xD;
          9. Active HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) infection or uncontrolled&#xD;
             infection.&#xD;
&#xD;
         10. Patients, in the opinion of investigators, may not be eligible or not able to comply&#xD;
             with the study.&#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>Lung-Ji Chang, PhD</last_name>
    <phone>+86(755)8672 5195</phone>
    <email>c@szgimi.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Seventh Affilliated Hospital, Sun Yat-Sen University</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518107</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bo Wang, MD</last_name>
      <phone>86-0755-23242570</phone>
      <email>wangb68377@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>June 10, 2020</last_update_submitted>
  <last_update_submitted_qc>June 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CART</keyword>
  <keyword>adoptive T cell transfer</keyword>
  <keyword>Her2</keyword>
  <keyword>GD2</keyword>
  <keyword>CD44V6</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast 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/NCT04430595
org study id: GIMI-IRB-20005
nct id: NCT04430595
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to assess the feasibility, safety and efficacy of multiple 4th
      generation CAR-T cells targeting Her2, GD2, and CD44v6 surface antigen in breast cancer.
      Another goal of the study is to learn more about the activities of the multi-CAR T cells and
      their persistency in the patients.
Breast cancer is one of the most frequent cancer types in women. The average risk of a woman
      in the United States developing breast cancer in her life is about 13%. That means that there
      is a 1 in 8 chance she will develop breast cancer. Human epidermal growth factor receptor-2
      (HER2) is one of the more well-researched genes in breast cancer so far. It has been reported
      that HER2 gene is overexpressed in 20% to 30% of breast cancer patients. HER2 is an important
      target for tumor gene therapy. In 2003, scientists confirmed the existence of breast cancer
      stem cells. In 2012, ganglioside GD2 was confirmed as an emerging marker of breast cancer
      stem cells. Targeting therapies for GD2 may help improve the survival rate and cure rate of
      breast cancer patients. Invasion and metastasis of tumor cells is the main cause of cancer
      death. CD44v6 is an adhesion molecule on the cell surface, which not only promotes
      epithelial-mesenchymal transition, degradation and remodeling of extracellular matrix, but
      also participates in organ-specific metastasis of tumor cells. Studies have shown that
      overexpression of CD44v6 is an important factor for the invasion and metastasis of breast
      cancer, and is closely related to the tumor size of the breast cancer, tumor staging, and
      lymph node metastasis. Therefore, CD44v6 may be an important target for the treatment of
      breast cancer. Using Her2-, GD2- and CD44v6-specific CAR-T cells may effectively improve the
      immunotherapy treatment, prevent tumor cells from escaping treatment, and achieve the effect
      of long-term disease relief.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with adverse events.
time frame: 3 year
description: Determine the toxicity profile the multi-4SCAR-T cells with Common Toxicity Criteria for Adverse Effects version 4.0
measure: Anti-tumor effects
time frame: 3 year
description: Disease status is defined by the image scan to get the outcomes such as Complete response/remission (CR), Very good partial response/remission (VGPR), etc.
measure: The expansion and persistence of CAR-T cells
time frame: 3 months
description: The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.
measure: Survival time of the patients
time frame: 3 year
description: The survival time of the patients treated with the multi-4SCAR T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.
arm group label: Multiple 4SCAR T cells to treat breast cancer
arm group type: Experimental
description: Multiple 4SCAR T cells to treat breast cancer
intervention type: Biological
intervention name: 4SCAR T cells
description: Infusion of 4SCAR-GD2, -Her2 and -CD44v6 CAR-T cells
arm group label: Multiple 4SCAR T cells to treat breast cancer
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Lung-Ji Chang, PhD
phone: +86(755)8672 5195
email: c@szgimi.org
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: No