xml: <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/NCT06016179</url>
    </required_header>
    <id_info>
      <org_study_id>2023-137</org_study_id>
      <nct_id>NCT06016179</nct_id>
    </id_info>
    <brief_title>Tocilizumab Delivered Via Pleural and Peritoneal Catheters in Patients With Advanced Metastatic Cancer</brief_title>
    <official_title>Phase I Study of the IL-6 Receptor Antagonist Tocilizumab Delivered Via Pleural and Peritoneal Catheters</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study to find out if tocilizumab can be safely infused into chest or&#xD;
        abdominal cavities of patients with malignancy ascites (MA) or malignant pleural effusions&#xD;
        (MPE). Patients will have a total of 4 doses, one dose administered each week. Each dose will&#xD;
        be greater than the previous one.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is an open label, Phase 1, intra-patient dose escalation study to determine the&#xD;
        feasibility of catheter-based intra-pleural and intra-peritoneal administration of&#xD;
        tocilizumab at doses up to 50μg/mL in patients with malignant pleural effusions (MPE) and&#xD;
        malignant ascites (MA) and to determine the frequency and type of adverse events.&#xD;
  &#xD;
        Tocilizumab is a monoclonal antibody inhibitor of the IL-6 receptor, FDA-approved for&#xD;
        intravenous administration in autoimmune disorders and cytokine release syndrome. The current&#xD;
        study aims to adapt this agent for intra-cavitary administration in patients&#xD;
  &#xD;
        A drain catheter will be placed in the patient as standard of care treatment. Following the&#xD;
        procedure, on that day and once a week for the following 3 weeks, tocilizumab will be&#xD;
        administered to the patient via the drain. Each treatment session will last about one hour,&#xD;
        and participants donate 6 milliliters (1 teaspoon) of blood before and after the treatment.&#xD;
        Fluid drained from the body cavity, which is normally discarded, will instead be collected&#xD;
        for analysis.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">December 2023</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>Intra-patient dose escalation administration of tocilizumab via pleural and peritoneal catheters</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Successful intra-cavitary administration of tocilizumab</measure>
      <time_frame>6 weeks</time_frame>
      <description>Number of patients with successful administration of tocilizumab</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Adverse Events</measure>
      <time_frame>6 weeks</time_frame>
      <description>To identify the frequency and type of adverse events (AE) following intrapleural or intraperitoneal administration of tocilizumab at doses up to 2.5 mg (intrapleural) or 25 mg (intraperitoneal) using CTCAE v5.0</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Analysis</measure>
      <time_frame>4 weeks</time_frame>
      <description>Measuring serum receptor occupancy levels</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Analysis</measure>
      <time_frame>4 weeks</time_frame>
      <description>Measuring intracavity fluid receptor occupancy levels</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biomarkers</measure>
      <time_frame>4 weeks</time_frame>
      <description>Change in Pleural cytokine concentrations</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biomarkers</measure>
      <time_frame>4 weeks</time_frame>
      <description>Change in Peritoneal Cytokine concentrations</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biomarkers</measure>
      <time_frame>4 weeks</time_frame>
      <description>Change in immune cell density</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Malignant Pleural Effusion</condition>
    <condition>Malignant Ascites</condition>
    <arm_group>
      <arm_group_label>Treatment Arm - intracavitary tocilizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Four incremental weekly intra-cavitary doses of tocilizumab starting at 0.5μg/mL and increasing to 1.6μg/mL, 5μg/mL and 50μg/mL once a week over four weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tocilizumab</intervention_name>
      <description>Each patient will receive four incremental weekly intra-cavitary doses of tocilizumab starting at 0.5μg/mL and increasing to 1.6μg/mL, 5μg/mL and 50μg/mL once a week over four weeks.</description>
      <arm_group_label>Treatment Arm - intracavitary tocilizumab</arm_group_label>
      <other_name>Actemra</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Subjects age 18-89 years old with pleural effusion or peritoneal ascites due to&#xD;
               metastatic cancer&#xD;
  &#xD;
            2. Scheduled to undergo standard-of-care placement of pleural or peritoneal drainage&#xD;
               catheter&#xD;
  &#xD;
            3. ECOG performance status: 0-2&#xD;
  &#xD;
            4. Able to read and sign consent form in English and provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Laboratory abnormalities that indicate clinically significant inflammatory process&#xD;
               AST/SGOT &gt; 1.5 times the upper limit of normal ALT/SGPT &gt; 1.5 times the upper limit of&#xD;
               normal Total bilirubin &gt; 1.5 times the upper limit of normal Creatinine &gt; 1.5 times&#xD;
               the upper limit of normal Hemoglobin &lt; 9 gm/dL White blood cell count &lt; 3,000/ mm3&#xD;
               Platelet count &lt; 70,000/mm3 Absolute neutrophil cell count &lt; 2,000 per mm3&#xD;
  &#xD;
            2. Subjects who are unable to comply with study procedures including travel for weekly&#xD;
               outpatient clinic visits&#xD;
  &#xD;
            3. Pregnant women&#xD;
  &#xD;
            4. Active immunotherapy within 30 days; concurrent chemotherapy or targeted therapy is&#xD;
               permitted but for patients with a history of prior immunotherapy, the most recent dose&#xD;
               should be &gt;30 days prior to the first treatment visit&#xD;
  &#xD;
            5. Investigational drug use within 30 days prior to first treatment dose&#xD;
  &#xD;
            6. History of systemic autoimmune disease&#xD;
  &#xD;
            7. Patient with known hypersensitivity to tocilizumab&#xD;
  &#xD;
            8. Active infection&#xD;
  &#xD;
            9. Medical contraindication or history of adverse reaction to acetaminophen or&#xD;
               diphenhydramine&#xD;
  &#xD;
               -&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>89 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Patrick Wagner, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Director of Complex General Surgical Oncology</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Patrick Wagner, MD</last_name>
      <phone>412-359-3731</phone>
      <email>patrick.wagner@ahn.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Laurie Dennis, RN, BS</last_name>
      <phone>412-330-6152</phone>
      <email>laurie.dennis@ahn.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Allegheny Health Network Cancer Institute</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15213</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)</investigator_affiliation>
      <investigator_full_name>Patrick Wagner, MD, FACS</investigator_full_name>
      <investigator_title>Investigator</investigator_title>
    </responsible_party>
    <keyword>Malignant Pleural Effusion</keyword>
    <keyword>Malignant Ascites</keyword>
    <keyword>Tocilizumab</keyword>
    <keyword>IL-6 receptor antagonist</keyword>
    <keyword>peritoneal cavity</keyword>
    <keyword>pleural cavity</keyword>
    <keyword>intraperitoneal</keyword>
    <keyword>intrapleural</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pleural Effusion, Malignant</mesh_term>
      <mesh_term>Pleural Effusion</mesh_term>
      <mesh_term>Ascites</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06016179
  org study id: 2023-137
  nct id: NCT06016179
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  The purpose of this study to find out if tocilizumab can be safely infused into chest or
        abdominal cavities of patients with malignancy ascites (MA) or malignant pleural effusions
        (MPE). Patients will have a total of 4 doses, one dose administered each week. Each dose will
        be greater than the previous one.
  This is an open label, Phase 1, intra-patient dose escalation study to determine the
        feasibility of catheter-based intra-pleural and intra-peritoneal administration of
        tocilizumab at doses up to 50μg/mL in patients with malignant pleural effusions (MPE) and
        malignant ascites (MA) and to determine the frequency and type of adverse events.
  
        Tocilizumab is a monoclonal antibody inhibitor of the IL-6 receptor, FDA-approved for
        intravenous administration in autoimmune disorders and cytokine release syndrome. The current
        study aims to adapt this agent for intra-cavitary administration in patients
  
        A drain catheter will be placed in the patient as standard of care treatment. Following the
        procedure, on that day and once a week for the following 3 weeks, tocilizumab will be
        administered to the patient via the drain. Each treatment session will last about one hour,
        and participants donate 6 milliliters (1 teaspoon) of blood before and after the treatment.
        Fluid drained from the body cavity, which is normally discarded, will instead be collected
        for analysis.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Intra-patient dose escalation administration of tocilizumab via pleural and peritoneal catheters
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Successful intra-cavitary administration of tocilizumab
  time frame: 6 weeks
  description: Number of patients with successful administration of tocilizumab
  measure: Adverse Events
  time frame: 6 weeks
  description: To identify the frequency and type of adverse events (AE) following intrapleural or intraperitoneal administration of tocilizumab at doses up to 2.5 mg (intrapleural) or 25 mg (intraperitoneal) using CTCAE v5.0
  measure: Pharmacokinetics Analysis
  time frame: 4 weeks
  description: Measuring serum receptor occupancy levels
  measure: Pharmacokinetics Analysis
  time frame: 4 weeks
  description: Measuring intracavity fluid receptor occupancy levels
  measure: Biomarkers
  time frame: 4 weeks
  description: Change in Pleural cytokine concentrations
  measure: Biomarkers
  time frame: 4 weeks
  description: Change in Peritoneal Cytokine concentrations
  measure: Biomarkers
  time frame: 4 weeks
  description: Change in immune cell density
  arm group label: Treatment Arm - intracavitary tocilizumab
  arm group type: Experimental
  description: Four incremental weekly intra-cavitary doses of tocilizumab starting at 0.5μg/mL and increasing to 1.6μg/mL, 5μg/mL and 50μg/mL once a week over four weeks.
  intervention type: Drug
  intervention name: Tocilizumab
  description: Each patient will receive four incremental weekly intra-cavitary doses of tocilizumab starting at 0.5μg/mL and increasing to 1.6μg/mL, 5μg/mL and 50μg/mL once a week over four weeks.
  arm group label: Treatment Arm - intracavitary tocilizumab
  other name: Actemra
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 89 Years
  healthy volunteers: No
  last name: Patrick Wagner, MD
  role: Principal Investigator
  affiliation: Director of Complex General Surgical Oncology
  last name: Patrick Wagner, MD
  phone: 412-359-3731
  email: patrick.wagner@ahn.org
  last name: Laurie Dennis, RN, BS
  phone: 412-330-6152
  email: laurie.dennis@ahn.org
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
  investigator full name: Patrick Wagner, MD, FACS
  investigator title: Investigator
  mesh term: Pleural Effusion, Malignant
  mesh term: Pleural Effusion
  mesh term: Ascites
  sharing ipd: No