<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/NCT02197169</url>
  </required_header>
  <id_info>
    <org_study_id>2401BT-IFN-001</org_study_id>
    <nct_id>NCT02197169</nct_id>
  </id_info>
  <brief_title>DNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors</brief_title>
  <acronym>TARGET-I</acronym>
  <official_title>A Phase 1b, Randomized, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) and Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma (TARGET-I)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>DNAtrix, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>DNAtrix, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant&#xD;
      primary brain tumor in adults and can be resistant to conventional therapies. The purpose of&#xD;
      this Phase Ib study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor&#xD;
      responds to one injection of DNX-2401, a genetically modified, conditionally replicative and&#xD;
      oncolytic human-derived adenovirus. DNX-2401 is delivered directly into the tumor where it&#xD;
      may establish an active infection by replicating in and killing tumor cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Enrollment has been completed for the randomized portion of the study with ongoing evaluation&#xD;
      of tumor response and safety. No additional subjects will be randomized or receive interferon&#xD;
      gamma (IFN-γ).&#xD;
&#xD;
      The non-randomized portion of the study is open for screening and enrollment. Eligible&#xD;
      subjects will receive a single intratumoral injection of DNX-2401 into a recurrent&#xD;
      glioblastoma or gliosarcoma brain tumor using the Alcyone MEMS Cannula (AMC™) System&#xD;
      (cannula). Tumor response and safety will be evaluated.&#xD;
&#xD;
      After receiving DNX-2401, subjects will return to the clinic for study visits at regular&#xD;
      intervals for safety monitoring, MRI scans and other assessments for up to 18 months.&#xD;
      Thereafter, they will be followed closely for safety and survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 11, 2014</start_date>
  <completion_date type="Actual">March 15, 2018</completion_date>
  <primary_completion_date type="Actual">March 15, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR) determined by MRI scan review</measure>
    <time_frame>1.5 years</time_frame>
    <description>Interval tumor size change will be measured</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings</measure>
    <time_frame>1.5 years</time_frame>
    <description>Events are classified using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma</measure>
    <time_frame>1.5 years</time_frame>
    <description>Laboratory test results and other assessments will be utilized to determine effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in responses to quality of life questionnaires</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Glioblastoma or Gliosarcoma</condition>
  <arm_group>
    <arm_group_label>DNX-2401 alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single intratumoral injection of DNX-2401</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DNX-2401 + Interferon gamma (IFN-γ)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Interferon gamma (IFN-γ) beginning at Day 14</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Single intratumoral injection of DNX-2401</intervention_name>
    <description>In the randomized group, following brain tumor biopsy and histological confirmation of recurrent glioblastoma/gliosarcoma, a single injection of DNX-2401 was administered directly into the brain tumor with or without subsequent interferon gamma (IFN-γ)&#xD;
No additional subjects will be randomized. A single intratumoral dose of DNX-2401 will be delivered by cannula.</description>
    <arm_group_label>DNX-2401 + Interferon gamma (IFN-γ)</arm_group_label>
    <arm_group_label>DNX-2401 alone</arm_group_label>
    <other_name>Oncolytic virus</other_name>
    <other_name>Genetically-modified adenovirus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interferon-gamma</intervention_name>
    <description>In the randomized group, a single injection of DNX-2401 was followed by interferon gamma (IFN-γ). No additional subjects will be randomized or receive IFN-γ following DNX-2401</description>
    <arm_group_label>DNX-2401 + Interferon gamma (IFN-γ)</arm_group_label>
    <other_name>Actimmune</other_name>
    <other_name>immunotherapy</other_name>
    <other_name>gamma interferon</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Glioblastoma or gliosarcoma in first or second recurrence only&#xD;
&#xD;
          -  Documented tumor recurrence or progression after failing prior surgical resection,&#xD;
             chemotherapy, or radiation&#xD;
&#xD;
          -  Tumor size greater than or equal to 1.0 cm in two perpendicular diameters&#xD;
&#xD;
          -  Not undergoing surgical resection or for whom gross total resection is not possible&#xD;
&#xD;
          -  Karnofsky Performance Status greater than or equal to 70%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Multiple intracranial malignant glioma lesions&#xD;
&#xD;
          -  Tumor location or involvement that would result in risk of ventricular penetration&#xD;
             during tumor injection&#xD;
&#xD;
          -  Tumor involving both hemispheres or that which involves the subependyma or suspected&#xD;
             cerebrospinal fluid dissemination&#xD;
&#xD;
          -  Tumor involving brain stem&#xD;
&#xD;
          -  Documented extracranial metastasis&#xD;
&#xD;
          -  Inability to undergo MRI&#xD;
&#xD;
          -  Pregnant or nursing females&#xD;
&#xD;
          -  Any medical condition that precludes the surgery necessary to administer DNX-2401 into&#xD;
             the tumor using the cannula&#xD;
&#xD;
          -  Immunocompromised subjects or those with autoimmune conditions, active hepatitis or&#xD;
             positive for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Li-Fraumeni Syndrome&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply as outlined in the relevant&#xD;
        protocol version&#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>Nam Tran, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Moffitt Cancer Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Karen Fink, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor University: Charles A. Sammons Cancer Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vinay Puduvalli, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University: James Cancer Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Frederick Lang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University: Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>July 20, 2014</study_first_submitted>
  <study_first_submitted_qc>July 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <last_update_submitted>July 12, 2018</last_update_submitted>
  <last_update_submitted_qc>July 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brain</keyword>
  <keyword>Brain Cancer</keyword>
  <keyword>Brain Neoplasms</keyword>
  <keyword>Central Nervous System Diseases</keyword>
  <keyword>Central Nervous System Neoplasms</keyword>
  <keyword>CNS</keyword>
  <keyword>Conditionally Replication-Competent Adenovirus</keyword>
  <keyword>DNX-2401</keyword>
  <keyword>Delta-24-RGD</keyword>
  <keyword>Glioma</keyword>
  <keyword>Glioblastoma</keyword>
  <keyword>Gliosarcoma</keyword>
  <keyword>Interferon gamma</keyword>
  <keyword>Malignant brain tumor</keyword>
  <keyword>Neoplasms, Neuroepithelial</keyword>
  <keyword>Neuroectodermal Tumors</keyword>
  <keyword>Neoplasms, Germ Cell and Embryonal</keyword>
  <keyword>Neoplasms by Histologic Type</keyword>
  <keyword>Neoplasms, Glandular and Epithelial</keyword>
  <keyword>Neoplasms, Nerve Tissue</keyword>
  <keyword>Nervous System Diseases</keyword>
  <keyword>Alcyone Lifesciences</keyword>
  <keyword>AMC™</keyword>
  <keyword>Cannula</keyword>
  <keyword>Alcyone MEMS Cannula (AMC™) System</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Gliosarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Interferon-gamma</mesh_term>
  </intervention_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/NCT02197169
org study id: 2401BT-IFN-001
nct id: NCT02197169
lead sponsor: 
has dmc: No
Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant
      primary brain tumor in adults and can be resistant to conventional therapies. The purpose of
      this Phase Ib study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor
      responds to one injection of DNX-2401, a genetically modified, conditionally replicative and
      oncolytic human-derived adenovirus. DNX-2401 is delivered directly into the tumor where it
      may establish an active infection by replicating in and killing tumor cells.
Enrollment has been completed for the randomized portion of the study with ongoing evaluation
      of tumor response and safety. No additional subjects will be randomized or receive interferon
      gamma (IFN-γ).

      The non-randomized portion of the study is open for screening and enrollment. Eligible
      subjects will receive a single intratumoral injection of DNX-2401 into a recurrent
      glioblastoma or gliosarcoma brain tumor using the Alcyone MEMS Cannula (AMC™) System
      (cannula). Tumor response and safety will be evaluated.

      After receiving DNX-2401, subjects will return to the clinic for study visits at regular
      intervals for safety monitoring, MRI scans and other assessments for up to 18 months.
      Thereafter, they will be followed closely for safety and survival.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR) determined by MRI scan review
time frame: 1.5 years
description: Interval tumor size change will be measured
measure: Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings
time frame: 1.5 years
description: Events are classified using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
measure: Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma
time frame: 1.5 years
description: Laboratory test results and other assessments will be utilized to determine effects
measure: Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment
time frame: 1.5 years
measure: Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).
time frame: 1.5 years
measure: Changes in responses to quality of life questionnaires
time frame: 1.5 years
arm group label: DNX-2401 alone
arm group type: Experimental
description: Single intratumoral injection of DNX-2401
arm group label: DNX-2401 + Interferon gamma (IFN-γ)
arm group type: Experimental
description: Interferon gamma (IFN-γ) beginning at Day 14
intervention type: Drug
intervention name: Single intratumoral injection of DNX-2401
description: In the randomized group, following brain tumor biopsy and histological confirmation of recurrent glioblastoma/gliosarcoma, a single injection of DNX-2401 was administered directly into the brain tumor with or without subsequent interferon gamma (IFN-γ)
No additional subjects will be randomized. A single intratumoral dose of DNX-2401 will be delivered by cannula.
arm group label: DNX-2401 + Interferon gamma (IFN-γ)
arm group label: DNX-2401 alone
other name: Oncolytic virus
other name: Genetically-modified adenovirus
intervention type: Drug
intervention name: Interferon-gamma
description: In the randomized group, a single injection of DNX-2401 was followed by interferon gamma (IFN-γ). No additional subjects will be randomized or receive IFN-γ following DNX-2401
arm group label: DNX-2401 + Interferon gamma (IFN-γ)
other name: Actimmune
other name: immunotherapy
other name: gamma interferon
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nam Tran, MD, PhD
role: Principal Investigator
affiliation: Moffitt Cancer Center
last name: Karen Fink, MD, PhD
role: Principal Investigator
affiliation: Baylor University: Charles A. Sammons Cancer Center
last name: Vinay Puduvalli, MBBS
role: Principal Investigator
affiliation: Ohio State University: James Cancer Center
last name: Frederick Lang, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Gliosarcoma
mesh term: Interferons
mesh term: Interferon-gamma