<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/NCT01721018</url>
  </required_header>
  <id_info>
    <org_study_id>1716-12</org_study_id>
    <nct_id>NCT01721018</nct_id>
  </id_info>
  <brief_title>Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma.</brief_title>
  <acronym>1716-12</acronym>
  <official_title>A Phase I/IIa Study of the Safety, Tolerability and Biological Effect of Single and Repeat Administration of the Selectively Replication-competent Herpes Simplex Virus HSV1716 Into the Tumor-bearing Pleural Cavity (Intrapleural) in Patients With Inoperable Malignant Pleural Mesothelioma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virttu Biologics Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Virttu Biologics Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      HSV1716, an oncolytic virus, is a mutant herpes simplex virus (HSV) type I, deleted in the&#xD;
      RL1 gene which encodes the protein ICP34.5.&#xD;
&#xD;
      Malignant mesothelioma is an aggressive, asbestos-related tumour of the pleural and&#xD;
      peritoneal cavities. It is a rare cancer which occurs in individuals who have been exposed to&#xD;
      asbestos, although it typically occurs decades after exposure (10-40 years later). Malignant&#xD;
      pleural mesothelioma forms plaques that are distributed on the surface of the pleural space&#xD;
      in the lung. Approximately 30% of patients require an indwelling pleural catheter for&#xD;
      drainage of pleural effusions. In this patient group, the indwelling catheter may be used to&#xD;
      facilitate loco-regional delivery of HSV1716 to the pleural space.&#xD;
&#xD;
      This study seeks to evaluate the safety and biological effects of single and multiple&#xD;
      administrations of HSV1716 in the treatment of malignant pleural mesothelioma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted in two parts. PART A is a single centre, single dose design, open&#xD;
      label. Patients with inoperable malignant pleural mesothelioma will receive a single dose of&#xD;
      HSV1716 by intrapleural administration. Delivery will be by direct administration via an&#xD;
      indwelling catheter into the pleural cavity. PART B is a single centre, repeat dose design,&#xD;
      open label. Two groups of three patients with inoperable malignant pleural mesothelioma will&#xD;
      receive 2 (group 1) or 4 (group 2) single doses of HSV1716 at weekly intervals.&#xD;
      Administration will be via an indwelling catheter into the pleural cavity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 14, 2016</completion_date>
  <primary_completion_date type="Actual">November 14, 2016</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>Safety and tolerability of HSV1716 given by single and repeat intrapleural administration in patients with inoperable malignant pleural mesothelioma.</measure>
    <time_frame>Dose limiting toxicities will be assessed at 28 days after last injection of HSV1716.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Obtain evidence of HSV1716 replication and lysis of malignant pleural mesothelioma cells through analysis of pleural fluid and serum samples for evidence of cell death and/or HSV1716 replication and/or changes in appropriate biomarkers.</measure>
    <time_frame>Samples will be collected at each outpatient visit up to day 29 (Part A), or day 50 (Part B).</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Tumour measurement as recorded by CT scans and assessed using the modified Response Criteria in Solid Tumors (RECIST) for MPM.</measure>
    <time_frame>CT scans at Baseline, day 29 and day 57.</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Malignant Pleural Mesothelioma</condition>
  <arm_group>
    <arm_group_label>HSV1716</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Arm Phase I/II study of intra-pleural HSV1716 administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HSV1716 Intra-pleural delivery</intervention_name>
    <arm_group_label>HSV1716</arm_group_label>
    <other_name>Seprehvir</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically proven malignant pleural mesothelioma&#xD;
&#xD;
          -  Patients with disease which is not amenable to potentially curative resection&#xD;
&#xD;
          -  Patients with pleural effusions and/or 'trapped lung' who (i) have an existing&#xD;
             indwelling pleural catheter for draining of excess pleural fluid or (ii) who require&#xD;
             the insertion of an indwelling pleural catheter to drain excess pleural fluid&#xD;
&#xD;
          -  Patients with a performance status ≤ 2 (ECOG)&#xD;
&#xD;
          -  Age of ≥ 18 years (at screening)&#xD;
&#xD;
          -  Ability to give written informed consent as evidenced by signature on the patient&#xD;
             consent form, to communicate well with the investigator and to comply with the&#xD;
             expectations of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients likely to require palliative radio- or chemotherapy within 30 days&#xD;
&#xD;
          -  Any evidence of uncontrolled cardiac or respiratory disease that would be a&#xD;
             contra-indication for virus administration&#xD;
&#xD;
          -  Any other serious medical or psychiatric disorder that would be a contra-indication&#xD;
             for virus administration&#xD;
&#xD;
          -  Acute active infection of any kind or other severe systemic disease or medical or&#xD;
             surgical condition that is deemed significant by the principal investigator&#xD;
&#xD;
          -  Patients with immunosuppressive disorders or on systemic steroids &gt; 5mg&#xD;
             prednisolone/day&#xD;
&#xD;
          -  Pregnancy: women of childbearing potential not taking adequate contraception, and&#xD;
             women who are breast feeding&#xD;
&#xD;
          -  Previous treatment with investigational viral therapy products&#xD;
&#xD;
          -  Administration of any unlicensed or investigational product within 8 weeks of entry to&#xD;
             the study&#xD;
&#xD;
          -  No prior or concurrent malignancy within 5 years other than basal cell carcinoma of&#xD;
             the skin or in situ neoplasia of the cervix uteri&#xD;
&#xD;
          -  Inadequate haematological function as defined by:&#xD;
&#xD;
        Haemoglobin (Hb) &lt; 10g/dl, Neutrophil Count &lt; 1.5 x 10e9/l, Platelets &lt; 100 x 10e9/l&#xD;
&#xD;
          -  Deranged liver function tests: serum bilirubin ≥ 1.5 x upper limit of normal reference&#xD;
             range for laboratory; transaminases ≥ 5 x upper limit of normal reference range&#xD;
&#xD;
          -  Patients with inadequate renal function: serum creatinine ≥ 1.5 x upper limit of&#xD;
             reference range for laboratory&#xD;
&#xD;
          -  Patients whose indwelling catheter is not of the type approved by the sponsor for use&#xD;
             in the study&#xD;
&#xD;
          -  Outwith any of the inclusion criteria above or considered unsuitable for entry into&#xD;
             the study in any other way at the discretion of the principal investigator&#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>Penella J Woll, MB BS PhD FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital, Sheffield, S10 2SJ, UK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust</name>
      <address>
        <city>Sheffield</city>
        <state>South Yorkshire</state>
        <zip>S10 2SJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Univeristy Hospital, NHS Greater Glasgow &amp; Clyde Health Board</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <last_update_submitted>June 8, 2017</last_update_submitted>
  <last_update_submitted_qc>June 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oncolytic virus</keyword>
  <keyword>HSV1716</keyword>
  <keyword>Mesothelioma</keyword>
  <keyword>MPM</keyword>
  <keyword>Woll</keyword>
  <keyword>Sheffield</keyword>
  <keyword>Weston Park</keyword>
  <keyword>Virttu</keyword>
  <keyword>Crusade</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesothelioma</mesh_term>
    <mesh_term>Mesothelioma, Malignant</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/NCT01721018
org study id: 1716-12
nct id: NCT01721018
lead sponsor: 
has dmc: No
HSV1716, an oncolytic virus, is a mutant herpes simplex virus (HSV) type I, deleted in the
      RL1 gene which encodes the protein ICP34.5.

      Malignant mesothelioma is an aggressive, asbestos-related tumour of the pleural and
      peritoneal cavities. It is a rare cancer which occurs in individuals who have been exposed to
      asbestos, although it typically occurs decades after exposure (10-40 years later). Malignant
      pleural mesothelioma forms plaques that are distributed on the surface of the pleural space
      in the lung. Approximately 30% of patients require an indwelling pleural catheter for
      drainage of pleural effusions. In this patient group, the indwelling catheter may be used to
      facilitate loco-regional delivery of HSV1716 to the pleural space.

      This study seeks to evaluate the safety and biological effects of single and multiple
      administrations of HSV1716 in the treatment of malignant pleural mesothelioma.
The study will be conducted in two parts. PART A is a single centre, single dose design, open
      label. Patients with inoperable malignant pleural mesothelioma will receive a single dose of
      HSV1716 by intrapleural administration. Delivery will be by direct administration via an
      indwelling catheter into the pleural cavity. PART B is a single centre, repeat dose design,
      open label. Two groups of three patients with inoperable malignant pleural mesothelioma will
      receive 2 (group 1) or 4 (group 2) single doses of HSV1716 at weekly intervals.
      Administration will be via an indwelling catheter into the pleural cavity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of HSV1716 given by single and repeat intrapleural administration in patients with inoperable malignant pleural mesothelioma.
time frame: Dose limiting toxicities will be assessed at 28 days after last injection of HSV1716.
measure: Obtain evidence of HSV1716 replication and lysis of malignant pleural mesothelioma cells through analysis of pleural fluid and serum samples for evidence of cell death and/or HSV1716 replication and/or changes in appropriate biomarkers.
time frame: Samples will be collected at each outpatient visit up to day 29 (Part A), or day 50 (Part B).
measure: Tumour measurement as recorded by CT scans and assessed using the modified Response Criteria in Solid Tumors (RECIST) for MPM.
time frame: CT scans at Baseline, day 29 and day 57.
arm group label: HSV1716
arm group type: Experimental
description: Single Arm Phase I/II study of intra-pleural HSV1716 administration.
intervention type: Biological
intervention name: HSV1716 Intra-pleural delivery
arm group label: HSV1716
other name: Seprehvir
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Penella J Woll, MB BS PhD FRCP
role: Principal Investigator
affiliation: Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital, Sheffield, S10 2SJ, UK
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant