<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/NCT03818165</url>
  </required_header>
  <id_info>
    <org_study_id>SOR-CART-CEA-001</org_study_id>
    <nct_id>NCT03818165</nct_id>
  </id_info>
  <brief_title>Phase 1b Study of CAR2Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases</brief_title>
  <acronym>AntiCEA_CART</acronym>
  <official_title>Phase 1b Study of the Efficacy and Safety of CAR2 Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases Resistant to Standard Therapy Using the HITM Method and Pressure Enabled Delivery Device</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sorrento Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sorrento Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is an open-label, single arm phase 1b safety study of CAR2 Anti-CEA CAR-T cell&#xD;
      hepatic arterial infusions for pancreatic carcinoma patients with carcinoembryonic antigen&#xD;
      positive (CEA+) liver metastases resistant to standard therapy who meet all other eligibility&#xD;
      criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will receive weekly 3 doses of CAR2 Anti-CEA CAR-T cells in each 28-day cycle by&#xD;
      hepatic arterial infusions using a Pressure Enhanced Delivery Device (PEDD) with low dose&#xD;
      systemic IL-2 support. Patients may receive up to 3 cycles of CAR2 Anti-CEA CAR-T cell&#xD;
      hepatic arterial infusions, per discretion of the investigator.&#xD;
&#xD;
      All patients who receive investigational CAR-T therapy will be included in the analyses and&#xD;
      summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Limited enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">July 29, 2019</start_date>
  <completion_date type="Actual">May 21, 2021</completion_date>
  <primary_completion_date type="Actual">January 19, 2020</primary_completion_date>
  <phase>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>
    <intervention_model_description>Three doses of CAR2 Anti-CEA CAR T Cells 1 x 10e10 cells by hepatic artery infusion (on Days 1, 8, and 15) of each 28-day cycle in the Treatment Period using the HITM method and Surefire device, with IL-2 systemic infusion. Patient may receive up to three 28-day cycles of CAR-T therapy in the Treatment Period.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess preliminary efficacy by overall survival</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by radiographic response rate using Response Evaluation Criteria in Solid Tumors (RECIST)</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, overall response rate will be assessed by radiographic scans using RECIST criteria. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by metabolic response rate using PET Response Criteria in Solid Tumors (PERCIST)</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, overall response rate will be assessed by radiographic scans using PERCIST criteria. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by response rate using Immune-related Response Criteria (irRC)</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, overall response rate will be assessed by radiographic scans using irRC. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by histologic response rate using pathologic response in biopsy specimens</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, overall response rate will be assessed by pathologic criteria using biopsies of the liver metastases and measuring necrosis and fibrosis. REsponse rates will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by serologic response rates by CEA levels</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, overall response rate will be assessed by serologic CEA levels. Response will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by serologic response rates by CA 19-9 levels</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, overall response rate will be assessed by serologic CA 19-9 levels. Response will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by duration of response in accordance with RECIST criteria</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, duration of response will be measured using radiologic scans and assessed according to RECIST criteria. This will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary efficacy by in-liver progression free survival (PFS)</measure>
    <time_frame>6 months</time_frame>
    <description>As a measure of activity, in-liver PFS will be assessed. The events for the assessment of PFS are disease progression and death events. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimate estimates and 95% confidence intervals will be provided where appropriate.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions.</measure>
    <time_frame>6 months</time_frame>
    <description>As an exploratory analysis, serum cytokine levels will be measured by ELISA to determine if increases in cytokines predict response and/or toxicity to liver arterial infusions.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess if neutrophil:lymphocyte ratios correlate with response</measure>
    <time_frame>6 months</time_frame>
    <description>As an exploratory analysis, neutrophil:lymphcyte ratios will be calculated to determine if they correlate with response and/or toxicity.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess the persistence of CAR-T cells circulating in blood over time</measure>
    <time_frame>6 months</time_frame>
    <description>As an exploratory analysis, circulating CAR-T cells will be analyzed to assess persistence of CAR-T cells during the treatment and observation phases of the study.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess the persistence of CAR-T cells in liver tumor biopsies over time</measure>
    <time_frame>6 months</time_frame>
    <description>As an exploratory analysis, the engraftment of CAR-T cells in planned liver tumor biopsies will be analyzed to assess persistence of CAR-T cells during the treatment and observation phases of the study.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess if circulating tumor cells (CTC) correlate with response</measure>
    <time_frame>6 months</time_frame>
    <description>As an exploratory analysis, levels of circulating tumor cells (CTC) will be determined to investigate if decreases in CTC levels correlate with response.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Metastatic Pancreatic Carcinoma</condition>
  <arm_group>
    <arm_group_label>CAR2 Anti-CEA CAR-T cell</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 doses of CAR2 Anti-CEA CAR-T cells for each cycle; up to 3 additional cycles received per investigator discretion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CAR2 Anti-CEA CAR-T cells</intervention_name>
    <description>doses will be delivered by hepatic arterial infusions using pressure enhanced delivery device (PEDD)</description>
    <arm_group_label>CAR2 Anti-CEA CAR-T cell</arm_group_label>
    <other_name>Surefire Precision Infusion System</other_name>
    <other_name>K171355</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must have documented CEA+ pancreatic adenocarcinoma liver metastases and have failed&#xD;
             greater than or equal to 1 line of conventional systemic therapy.&#xD;
&#xD;
          -  Must have at least evaluable liver metastases.&#xD;
&#xD;
          -  Must have a life-expectancy at least 12 weeks.&#xD;
&#xD;
          -  Patients must be willing and able to comply with the study schedule and all other&#xD;
             protocol requirements.&#xD;
&#xD;
          -  Females of childbearing potential must have 2 negative pregnancy tests, agree to&#xD;
             pregnancy tests during the study, and sexually active female and male patients must be&#xD;
             willing to use an effective birth control method to avoid pregnancy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have received an investigational study drug within 14 days of&#xD;
             leukapheresis or 28 days before receiving first dose of study drug.&#xD;
&#xD;
          -  Subjects who have received any approved anticancer medication within 14 days of&#xD;
             leukapheresis or 14 days before receiving the first dose of study drug.&#xD;
&#xD;
          -  Have any unresolved toxicity greater than Grade 2 from previous anticancer therapy.&#xD;
&#xD;
          -  Have a history of confirmed metastases outside the peritoneal cavity, lungs, or liver.&#xD;
&#xD;
          -  More than 50% replacement of one or both liver lobes with tumor.&#xD;
&#xD;
          -  Has tumor causing biliary obstruction not amenable to stenting.&#xD;
&#xD;
          -  Have a high volume of lung or peritoneal metastases.&#xD;
&#xD;
          -  Has received any CAR cell line therapies.&#xD;
&#xD;
          -  Has any clinically significant low baseline lab results for hemoglobin, platelet&#xD;
             counts, and neutrophil counts at screening.&#xD;
&#xD;
          -  Has untreated or ongoing intra-abdominal infection or bowel obstruction.&#xD;
&#xD;
          -  Has any clinically significant elevated baseline lab results for serum creatinine,&#xD;
             AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed&#xD;
             to Gilbert's syndrome), and alkaline phosphatase at screening regardless of causality.&#xD;
&#xD;
          -  Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of&#xD;
             chronic hepatitis B or C.&#xD;
&#xD;
          -  Female patients who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Have active bacterial, viral, or fungal infections.&#xD;
&#xD;
          -  Has any significant medical condition, laboratory abnormality, or psychiatric illness&#xD;
             that would prevent study participation.&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) &lt; 40%.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven C Katz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Roger Williams Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Roger Williams Medical Center</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>January 12, 2023</last_update_submitted>
  <last_update_submitted_qc>January 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pancreatic carcinoma</keyword>
  <keyword>Cacinomaembryonic antigen postive (CEA +)</keyword>
  <keyword>liver metastases</keyword>
  <keyword>pancreatic cancer</keyword>
  <keyword>CEA</keyword>
  <keyword>metastatic pancreatic carcinoma</keyword>
  <keyword>metastatic pancreatic cancer</keyword>
  <keyword>phase 1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT03818165
org study id: SOR-CART-CEA-001
nct id: NCT03818165
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is an open-label, single arm phase 1b safety study of CAR2 Anti-CEA CAR-T cell
      hepatic arterial infusions for pancreatic carcinoma patients with carcinoembryonic antigen
      positive (CEA+) liver metastases resistant to standard therapy who meet all other eligibility
      criteria.
Patients will receive weekly 3 doses of CAR2 Anti-CEA CAR-T cells in each 28-day cycle by
      hepatic arterial infusions using a Pressure Enhanced Delivery Device (PEDD) with low dose
      systemic IL-2 support. Patients may receive up to 3 cycles of CAR2 Anti-CEA CAR-T cell
      hepatic arterial infusions, per discretion of the investigator.

      All patients who receive investigational CAR-T therapy will be included in the analyses and
      summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Three doses of CAR2 Anti-CEA CAR T Cells 1 x 10e10 cells by hepatic artery infusion (on Days 1, 8, and 15) of each 28-day cycle in the Treatment Period using the HITM method and Surefire device, with IL-2 systemic infusion. Patient may receive up to three 28-day cycles of CAR-T therapy in the Treatment Period.
primary purpose: Treatment
masking: None (Open Label)
measure: Assess preliminary efficacy by overall survival
time frame: 6 months
description: As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable.
measure: Assess preliminary efficacy by radiographic response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: 6 months
description: As a measure of activity, overall response rate will be assessed by radiographic scans using RECIST criteria. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
measure: Assess preliminary efficacy by metabolic response rate using PET Response Criteria in Solid Tumors (PERCIST)
time frame: 6 months
description: As a measure of activity, overall response rate will be assessed by radiographic scans using PERCIST criteria. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
measure: Assess preliminary efficacy by response rate using Immune-related Response Criteria (irRC)
time frame: 6 months
description: As a measure of activity, overall response rate will be assessed by radiographic scans using irRC. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
measure: Assess preliminary efficacy by histologic response rate using pathologic response in biopsy specimens
time frame: 6 months
description: As a measure of activity, overall response rate will be assessed by pathologic criteria using biopsies of the liver metastases and measuring necrosis and fibrosis. REsponse rates will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
measure: Assess preliminary efficacy by serologic response rates by CEA levels
time frame: 6 months
description: As a measure of activity, overall response rate will be assessed by serologic CEA levels. Response will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
measure: Assess preliminary efficacy by serologic response rates by CA 19-9 levels
time frame: 6 months
description: As a measure of activity, overall response rate will be assessed by serologic CA 19-9 levels. Response will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
measure: Assess preliminary efficacy by duration of response in accordance with RECIST criteria
time frame: 6 months
description: As a measure of activity, duration of response will be measured using radiologic scans and assessed according to RECIST criteria. This will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
measure: Assess preliminary efficacy by in-liver progression free survival (PFS)
time frame: 6 months
description: As a measure of activity, in-liver PFS will be assessed. The events for the assessment of PFS are disease progression and death events. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimate estimates and 95% confidence intervals will be provided where appropriate.
measure: Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions.
time frame: 6 months
description: As an exploratory analysis, serum cytokine levels will be measured by ELISA to determine if increases in cytokines predict response and/or toxicity to liver arterial infusions.
measure: Assess if neutrophil:lymphocyte ratios correlate with response
time frame: 6 months
description: As an exploratory analysis, neutrophil:lymphcyte ratios will be calculated to determine if they correlate with response and/or toxicity.
measure: Assess the persistence of CAR-T cells circulating in blood over time
time frame: 6 months
description: As an exploratory analysis, circulating CAR-T cells will be analyzed to assess persistence of CAR-T cells during the treatment and observation phases of the study.
measure: Assess the persistence of CAR-T cells in liver tumor biopsies over time
time frame: 6 months
description: As an exploratory analysis, the engraftment of CAR-T cells in planned liver tumor biopsies will be analyzed to assess persistence of CAR-T cells during the treatment and observation phases of the study.
measure: Assess if circulating tumor cells (CTC) correlate with response
time frame: 6 months
description: As an exploratory analysis, levels of circulating tumor cells (CTC) will be determined to investigate if decreases in CTC levels correlate with response.
arm group label: CAR2 Anti-CEA CAR-T cell
arm group type: Experimental
description: 3 doses of CAR2 Anti-CEA CAR-T cells for each cycle; up to 3 additional cycles received per investigator discretion
intervention type: Biological
intervention name: CAR2 Anti-CEA CAR-T cells
description: doses will be delivered by hepatic arterial infusions using pressure enhanced delivery device (PEDD)
arm group label: CAR2 Anti-CEA CAR-T cell
other name: Surefire Precision Infusion System
other name: K171355
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven C Katz, MD
role: Principal Investigator
affiliation: Roger Williams Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neoplasm Metastasis
mesh term: Pancreatic Neoplasms