<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/NCT02986178</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00077024</org_study_id>
    <nct_id>NCT02986178</nct_id>
  </id_info>
  <brief_title>PVSRIPO in Recurrent Malignant Glioma</brief_title>
  <official_title>A Multicenter Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in Recurrent WHO Grade IV Malignant Glioma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istari Oncology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Istari Oncology, 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 is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients&#xD;
      with recurrent World Health Organization (WHO) grade IV malignant glioma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients&#xD;
      with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of&#xD;
      this study is to investigate the safety and efficacy (anti-tumor response and survival) of&#xD;
      PVSRIPO in recurrent WHO grade IV malignant glioma.&#xD;
&#xD;
      Patients will be administered PVSRIPO intratumorally via convection-enhanced delivery (CED)&#xD;
      using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment&#xD;
      with PVSRIPO is allowed, provided retreatment eligibility criteria are met.&#xD;
&#xD;
      All patients who receive PVSRIPO treatment will be included in efficacy and safety analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <phase>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>Objective Radiographic Response Rate</measure>
    <time_frame>24 months after initial PVSRIPO infusion and through study completion.</time_frame>
    <description>Assess objective anti-tumor response based on iRANO criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Radiographic Response Rate</measure>
    <time_frame>36 months after initial PVSRIPO infusion and through study completion.</time_frame>
    <description>Assess objective anti-tumor response based on iRANO criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Objective Radiographic Response</measure>
    <time_frame>24 months after initial PVSRIPO infusion and through study completion.</time_frame>
    <description>Assess time of confirmed response to confirmed progressive disease/death.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Objective Radiographic Response</measure>
    <time_frame>36 months after initial PVSRIPO infusion and through study completion.</time_frame>
    <description>Assess time of confirmed response to confirmed progressive disease/death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>24 and 36 months after initial PVSRIPO infusion and through study completion.</time_frame>
    <description>Overall Survival, relative to external control group(s)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Landmark Survival</measure>
    <time_frame>24 and 36 months post-infusion and through study completion.</time_frame>
    <description>Overall survival at 24 and 36 months and greater</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate Following PVSRIPO Infusion</measure>
    <time_frame>24 and 36 months after initial PVSRIPO infusion and through study completion.</time_frame>
    <description>The percentage of patients classified as non-progressive by radiographic response based on standard criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of PVSRIPO: proportion of patients who experience grade 3, 4, or 5 AEs</measure>
    <time_frame>While on study; average of 12 to 36 months after initial PVSRIPO infusion.</time_frame>
    <description>Within each cohort for those randomized prior to protocol version 7, as well as for those patients retreated with PVSRIPO, the proportion of patients who experience grade 3, 4, or 5 AEs that are possibly, probably, and definitely related to protocol treatment will be estimated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">122</enrollment>
  <condition>Malignant Glioma</condition>
  <arm_group>
    <arm_group_label>Polio/Rhinovirus Recombinant (PVSRIPO)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Polio/Rhinovirus Recombinant (PVSRIPO)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PVSRIPO</intervention_name>
    <description>A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)</description>
    <arm_group_label>Polio/Rhinovirus Recombinant (PVSRIPO)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA SUMMARY:&#xD;
&#xD;
          1. Patients must have a recurrent (first or second recurrence only, including this&#xD;
             recurrence; transformation from a lower grade tumor to a WHO grade IV malignant glioma&#xD;
             will be considered a first recurrence) supratentorial WHO grade IV malignant glioma&#xD;
             based on imaging studies with measurable disease (a minimum measurement of 1 cm and&#xD;
             maximum of 5.5 cm of contrast-enhancing tumor) with prior histopathology consistent&#xD;
             with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the&#xD;
             neuropathologist's designate.&#xD;
&#xD;
          2. Male patients who are sexually active are eligible if he and/or his partner(s) meets&#xD;
             the criteria outlined in the protocol. Female subjects are eligible if he and/or his&#xD;
             partner(s) meets the criteria outlined in the protocol.&#xD;
&#xD;
          3. Age ≥ 18 years of age.&#xD;
&#xD;
          4. Karnofsky Performance Status (KPS) Score ≥ 70%.&#xD;
&#xD;
          5. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.&#xD;
&#xD;
          6. Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic&#xD;
             pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy.&#xD;
&#xD;
          7. Neutrophil count ≥ 1000 prior to biopsy.&#xD;
&#xD;
          8. Hemoglobin ≥ 9 prior to biopsy.&#xD;
&#xD;
          9. Platelet count ≥ 100,000/μL unsupported is necessary for eligibility on study;&#xD;
             however, because of risks of intracranial hemorrhage with catheter placement, platelet&#xD;
             count ≥ 125,000/μL is required for the patient to undergo biopsy and catheter&#xD;
             insertion, which can be attained with the help of platelet transfusion.&#xD;
&#xD;
         10. Creatinine ≤ 1.2 x normal range prior to biopsy.&#xD;
&#xD;
         11. Positive serum anti-PV titer prior to biopsy.&#xD;
&#xD;
         12. The patient must have received a boost immunization with trivalent inactivated IPOL™&#xD;
             (Sanofi-Pasteur) at least 1 week, but less than 6 weeks, prior to administration of&#xD;
             the study agent.&#xD;
&#xD;
         13. At the time of biopsy, prior to administration of virus, the presence of recurrent&#xD;
             tumor must be confirmed by histopathological analysis.&#xD;
&#xD;
         14. A signed IRB-approve informed consent form (ICF).&#xD;
&#xD;
         15. Able to undergo brain MRI with and without contrast.&#xD;
&#xD;
        EXCLUSION CRITERIA SUMMARY:&#xD;
&#xD;
          1. Females who are pregnant or breast-feeding.&#xD;
&#xD;
          2. Patients with an impending, life-threatening cerebral herniation syndrome, based on&#xD;
             the assessment of the study neurosurgeons, their designate, and the reviewer&#xD;
             designated by the sponsor.&#xD;
&#xD;
          3. Patients with severe, active co-morbidity, defined as in the protocol.&#xD;
&#xD;
          4. Patients with a previous history of neurological complications due to PV infection.&#xD;
&#xD;
          5. Patients who have not recovered from the toxic effects of prior chemo- and/or&#xD;
             radiation therapy. Guidelines for this recovery period are dependent upon the specific&#xD;
             therapeutic agent being used.&#xD;
&#xD;
          6. Patients may not have received tumor treating fields (≤ 1 week), chemotherapy or&#xD;
             bevacizumab ≤ 4 weeks [except for nitrosourea and lomustine (≤ 6 weeks); metronomic&#xD;
             dosed chemotherapy, such as daily temozolomide, etoposide or cyclophosphamide (≤ 1&#xD;
             week)] prior to starting the study drug.&#xD;
&#xD;
          7. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study&#xD;
             drug unless patients have recovered from side effects of such therapy.&#xD;
&#xD;
          8. Patients may not be less than 12 weeks from radiation therapy of the brain, unless&#xD;
             progressive disease outside of the radiation field or 2 progressive scans at least 4&#xD;
             weeks apart or histopathologic confirmation.&#xD;
&#xD;
          9. Prior to enrollment, has not completed all standard of care treatments, including&#xD;
             surgical procedure and radiation therapy (at least 59Gy) as outlined in the protocol.&#xD;
&#xD;
         10. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord;&#xD;
             radiological evidence of multiple areas of active (growing) disease (active multifocal&#xD;
             disease); tumors with contrast-enhancing tumor component crossing the midline&#xD;
             (crossing the corpus callosum); extensive subependymal disease (tumor touching&#xD;
             subependymal space is allowed); or extensive leptomeningeal disease (tumor touching&#xD;
             leptomeninges is allowed).&#xD;
&#xD;
         11. Patients with undetectable anti-tetanus toxoid immunoglobulin G (IgG).&#xD;
&#xD;
         12. Patients with known history of agammaglobulinemia.&#xD;
&#xD;
         13. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to&#xD;
             admission for PVSRIPO infusion.&#xD;
&#xD;
         14. Patients with worsening steroid myopathy (history of gradual progression of bilateral&#xD;
             proximal muscle weakness, and atrophy of proximal muscle groups).&#xD;
&#xD;
         15. Patients with prior, unrelated malignancy requiring current active treatment with the&#xD;
             exception of cervical carcinoma in situ and adequately treated basal cell or squamous&#xD;
             cell carcinoma of the skin.&#xD;
&#xD;
         16. For patients randomized prior to V7, a known history of hypersensitivity to lomustine,&#xD;
             dacarbazine, or any components of lomustine.&#xD;
&#xD;
         17. Patients with active autoimmune disease requiring systemic immunomodulatory treatment&#xD;
             within the past 3 months.&#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>Dina Randazzo, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSF Neurological Surgery</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94941</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist MD Anderson Cancer Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Preston Robert Tisch Brain Tumor Center at Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://tischbraintumorcenter.duke.edu/</url>
    <description>The Preston Robert Tisch Brain Tumor Center at Duke University</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>June 28, 2022</last_update_submitted>
  <last_update_submitted_qc>June 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glioblastoma</keyword>
  <keyword>Glioma</keyword>
  <keyword>PVSRIPO</keyword>
  <keyword>Duke</keyword>
  <keyword>Pro00077024</keyword>
  <keyword>Brain tumor</keyword>
  <keyword>Istari</keyword>
  <keyword>Recurrent</keyword>
  <keyword>GBM</keyword>
  <keyword>rGBM</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</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/NCT02986178
org study id: Pro00077024
nct id: NCT02986178
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients
      with recurrent World Health Organization (WHO) grade IV malignant glioma.
This is a Phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients
      with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of
      this study is to investigate the safety and efficacy (anti-tumor response and survival) of
      PVSRIPO in recurrent WHO grade IV malignant glioma.

      Patients will be administered PVSRIPO intratumorally via convection-enhanced delivery (CED)
      using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment
      with PVSRIPO is allowed, provided retreatment eligibility criteria are met.

      All patients who receive PVSRIPO treatment will be included in efficacy and safety analyses.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Radiographic Response Rate
time frame: 24 months after initial PVSRIPO infusion and through study completion.
description: Assess objective anti-tumor response based on iRANO criteria.
measure: Objective Radiographic Response Rate
time frame: 36 months after initial PVSRIPO infusion and through study completion.
description: Assess objective anti-tumor response based on iRANO criteria.
measure: Duration of Objective Radiographic Response
time frame: 24 months after initial PVSRIPO infusion and through study completion.
description: Assess time of confirmed response to confirmed progressive disease/death.
measure: Duration of Objective Radiographic Response
time frame: 36 months after initial PVSRIPO infusion and through study completion.
description: Assess time of confirmed response to confirmed progressive disease/death.
measure: Overall Survival
time frame: 24 and 36 months after initial PVSRIPO infusion and through study completion.
description: Overall Survival, relative to external control group(s)
measure: Landmark Survival
time frame: 24 and 36 months post-infusion and through study completion.
description: Overall survival at 24 and 36 months and greater
measure: Disease Control Rate Following PVSRIPO Infusion
time frame: 24 and 36 months after initial PVSRIPO infusion and through study completion.
description: The percentage of patients classified as non-progressive by radiographic response based on standard criteria.
measure: Safety of PVSRIPO: proportion of patients who experience grade 3, 4, or 5 AEs
time frame: While on study; average of 12 to 36 months after initial PVSRIPO infusion.
description: Within each cohort for those randomized prior to protocol version 7, as well as for those patients retreated with PVSRIPO, the proportion of patients who experience grade 3, 4, or 5 AEs that are possibly, probably, and definitely related to protocol treatment will be estimated.
arm group label: Polio/Rhinovirus Recombinant (PVSRIPO)
arm group type: Experimental
description: Polio/Rhinovirus Recombinant (PVSRIPO)
intervention type: Biological
intervention name: PVSRIPO
description: A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)
arm group label: Polio/Rhinovirus Recombinant (PVSRIPO)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dina Randazzo, DO
role: Principal Investigator
affiliation: Duke University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://tischbraintumorcenter.duke.edu/
description: The Preston Robert Tisch Brain Tumor Center at Duke University
responsible party type: Sponsor
mesh term: Glioma
sharing ipd: No