<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/NCT03029871</url>
  </required_header>
  <id_info>
    <org_study_id>10835</org_study_id>
    <nct_id>NCT03029871</nct_id>
  </id_info>
  <brief_title>Oncolytic Adenovirus-Mediated Gene Therapy for Lung Cancer</brief_title>
  <acronym>NSCLC</acronym>
  <official_title>Phase 1 Trial of Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Combination With Stereotactic Body Radiation Therapy (SBRT) in Clinical Stage 1/11A (T1A-T2B) Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Benjamin Movsas, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Henry Ford Health System</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and&#xD;
      maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in&#xD;
      combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. To accomplish&#xD;
      this objective, 9 subjects will be enrolled in the study. We hypothesize that the combined&#xD;
      treatment will demonstrate acceptable toxicity, and that it will be feasible to quantify&#xD;
      adenovirus-mediated HSV-1 TK gene expression in the lung by PET. This phase 1 trial will lay&#xD;
      the foundation for a follow-up phase 2 trial designed to examine efficacy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a -&#xD;
      T2b) NSCLC with tumors measuring &gt; 2 to ≤ 5 cm will receive a single intratumoral injection&#xD;
      of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011&#xD;
      vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus&#xD;
      will be injected either transbronchially (central tumors) or percutaneously under computed&#xD;
      tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered&#xD;
      (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy&#xD;
      along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus&#xD;
      injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo&#xD;
      PET imaging to quantify HSV-1 TK gene expression. Toxicity assessments will occur twice a&#xD;
      week for the first 2 weeks and then at scheduled follow-up visits through 60 months. The&#xD;
      primary endpoint is toxicity. Secondary endpoints include 1) tumor (radiological) response,&#xD;
      2) local, regional, and distal tumor control, 3) progression-free and overall survival, and&#xD;
      4) quality of life. Exploratory endpoints include 1) intensity, persistence, and&#xD;
      biodistribution of HSV-1 TK gene expression, and 2) association of select serum biomarkers&#xD;
      with toxicity and tumor response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No participants were enrolled&#xD;
  </why_stopped>
  <start_date type="Actual">January 13, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Nine subjects (3 cohorts, 3 subjects/cohort)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Toxicity and maximum tolerated dose</measure>
    <time_frame>60 days</time_frame>
    <description>Treatment-related adverse events (CTCAE v4.03)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>3 months to 5 years</time_frame>
    <description>RECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>3 months to 5 years</time_frame>
    <description>Progression-free and overall</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>3 months to 5 years</time_frame>
    <description>FACT-TOI (Functional Assessment of Cancer Therapy-Trial Outcome Index)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Non-small Cell Lung Cancer Stage I</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a - T2b) NSCLC with tumors measuring &gt; 2 to ≤ 5 cm will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011 vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus will be injected either transbronchially (central tumors) or percutaneously under computed tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify HSV-1 TK gene expression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ad5-yCD/mutTKSR39rep-ADP Adenovirus</intervention_name>
    <description>oncolytic adenovirus</description>
    <arm_group_label>Arm 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically (histologically or cytologically) proven diagnosis of NSCLC.&#xD;
&#xD;
          -  Clinical stage I/IIA (T1a - T2b; AJCC Staging 7th edition) with a tumor size &gt; 1 cm to&#xD;
             ≤ 6 cm in diameter (long axis) based on the following minimum diagnostic workup:&#xD;
&#xD;
        Note: Subjects may have M0 or MX status (e.g., lung nodules that are being observed). Known&#xD;
        M1 disease is excluded. Subjects may have only one target lesion for SBRT.&#xD;
&#xD;
          -  Evaluation at lung multi-disciplinary tumor board with recommendation for SBRT within&#xD;
             12 weeks of registration.&#xD;
&#xD;
          -  Whole body positron emission tomography (PET/CT) scan within 12 weeks of registration&#xD;
             using [18F]-FDG with adequate visualization of the primary tumor and draining lymph&#xD;
             node basins in the hilar and mediastinal regions.&#xD;
&#xD;
        Mediastinal lymph node sampling by any technique is allowed but not required. Subjects with&#xD;
        &gt; 1.5 cm mediastinal lymph nodes on CT or abnormal PET (including suspicious but&#xD;
        non-diagnostic uptake) may still be eligible if directed tissue biopsies of abnormally&#xD;
        identified areas are negative for cancer.&#xD;
&#xD;
          -  Zubrod Performance Status 0 - 2 with 4 weeks of registration.&#xD;
&#xD;
          -  Age ≥ 18.&#xD;
&#xD;
          -  Subjects must have adequate baseline organ function, as assessed by the following&#xD;
             laboratory values, within 30 days before initiating the study therapy:&#xD;
&#xD;
          -  Adequate renal function with serum creatinine ≤ 1.5 mg/dL or creatinine clearance &gt;50&#xD;
             mL/min/m2.&#xD;
&#xD;
          -  Platelet count &gt; 100,000/μL.&#xD;
&#xD;
          -  Absolute neutrophil count &gt; 1,000/μL.&#xD;
&#xD;
          -  Hemoglobin &gt; 10.0 g/dL.&#xD;
&#xD;
          -  Bilirubin &gt; 1.5 mg/dL&#xD;
&#xD;
          -  AST/SGOT and ALT/SGPT &lt; 3.0 times upper limit of normal (ULN).&#xD;
&#xD;
          -  Negative serum or urine pregnancy test within 72 hours prior to the adenovirus&#xD;
             injection for women of childbearing potential.&#xD;
&#xD;
          -  Women of childbearing potential and male participants must agree to use a medically&#xD;
             effective means of birth control throughout and for 60 days beyond the treatment phase&#xD;
             of the study.&#xD;
&#xD;
          -  Subjects must possess the ability to give informed consent and express a willingness&#xD;
             to meet all of the expected requirements of the protocol for the duration of the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 2 years (e.g., carcinomas in situ of the breast, oral cavity, or&#xD;
             cervix are permissible). Subjects with previous lung cancer are permitted if the&#xD;
             subject is disease-free for a minimum of 2 years or if this is a solitary recurrence&#xD;
             in the lung measuring &gt; 2 cm and ≤ 5 cm after surgery.&#xD;
&#xD;
          -  Any known metastatic disease. Subjects may have MX status (e.g., lung nodules that are&#xD;
             being observed).&#xD;
&#xD;
          -  Prior radiotherapy to the region of the study cancer that would result in overlap of&#xD;
             radiation therapy fields.&#xD;
&#xD;
          -  Prior chemotherapy for the study cancer.&#xD;
&#xD;
          -  Plans for the subject to receive other local therapy (including standard fractionated&#xD;
             radiotherapy and/or surgery and/or other local ablative therapies) while on this&#xD;
             study, except in the case of disease progression.&#xD;
&#xD;
          -  Plans for the subject to receive systemic therapy (including standard chemotherapy or&#xD;
             biologic targeted agents), while on this study, except in the case of disease&#xD;
             progression.&#xD;
&#xD;
          -  Acute infection. Acute infection is defined by any viral, bacterial, or fungal&#xD;
             infection that requires specific therapy within 72 hours of initiation of the study&#xD;
             therapy.&#xD;
&#xD;
          -  Previous history of liver disease including hepatitis.&#xD;
&#xD;
          -  Immunosuppressive therapy including systemic corticosteroids. Use of inhaled and&#xD;
             topical corticosteroids is permitted.&#xD;
&#xD;
          -  Impaired immunity or susceptibility to serious viral infections.&#xD;
&#xD;
          -  Allergy to any product used in the protocol.&#xD;
&#xD;
          -  Serious medical or psychiatric illness or concomitant medication, which, in the&#xD;
             judgment of the principal investigator, might interfere with the subject's ability to&#xD;
             respond to or tolerate the treatment or complete the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>August 9, 2019</last_update_submitted>
  <last_update_submitted_qc>August 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Henry Ford Health System</investigator_affiliation>
    <investigator_full_name>Benjamin Movsas, M.D.</investigator_full_name>
    <investigator_title>Chair, Department of Radiation Oncology</investigator_title>
  </responsible_party>
  <keyword>lung cancer</keyword>
  <keyword>adenovirus</keyword>
  <keyword>gene therapy</keyword>
  <keyword>SBRT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenoviridae Infections</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</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/NCT03029871
org study id: 10835
nct id: NCT03029871
lead sponsor: 
has dmc: Yes
The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and
      maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in
      combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. To accomplish
      this objective, 9 subjects will be enrolled in the study. We hypothesize that the combined
      treatment will demonstrate acceptable toxicity, and that it will be feasible to quantify
      adenovirus-mediated HSV-1 TK gene expression in the lung by PET. This phase 1 trial will lay
      the foundation for a follow-up phase 2 trial designed to examine efficacy.
Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a -
      T2b) NSCLC with tumors measuring > 2 to ≤ 5 cm will receive a single intratumoral injection
      of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011
      vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus
      will be injected either transbronchially (central tumors) or percutaneously under computed
      tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered
      (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy
      along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus
      injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo
      PET imaging to quantify HSV-1 TK gene expression. Toxicity assessments will occur twice a
      week for the first 2 weeks and then at scheduled follow-up visits through 60 months. The
      primary endpoint is toxicity. Secondary endpoints include 1) tumor (radiological) response,
      2) local, regional, and distal tumor control, 3) progression-free and overall survival, and
      4) quality of life. Exploratory endpoints include 1) intensity, persistence, and
      biodistribution of HSV-1 TK gene expression, and 2) association of select serum biomarkers
      with toxicity and tumor response.
intervention model: Sequential Assignment
intervention model description: Nine subjects (3 cohorts, 3 subjects/cohort)
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicity and maximum tolerated dose
time frame: 60 days
description: Treatment-related adverse events (CTCAE v4.03)
measure: Tumor response
time frame: 3 months to 5 years
description: RECIST
measure: Survival
time frame: 3 months to 5 years
description: Progression-free and overall
measure: Quality of Life
time frame: 3 months to 5 years
description: FACT-TOI (Functional Assessment of Cancer Therapy-Trial Outcome Index)
arm group label: Arm 1
arm group type: Experimental
description: Nine subjects (3 cohorts, 3 subjects/cohort) with medically inoperable stage I/IIA (T1a - T2b) NSCLC with tumors measuring > 2 to ≤ 5 cm will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels (1 x 1011 vp, 3 x 1011 vp, 1 x 1012 vp). Depending on the location of the target lesion, the adenovirus will be injected either transbronchially (central tumors) or percutaneously under computed tomography (CT)-guidance (peripheral tumors). Two days later, subjects will be administered (orally) a 10 day course of 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy along with 48 Gy (4 fractions of 12 Gy) of SBRT. Prior to and following the adenovirus injection, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify HSV-1 TK gene expression.
intervention type: Biological
intervention name: Ad5-yCD/mutTKSR39rep-ADP Adenovirus
description: oncolytic adenovirus
arm group label: Arm 1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Henry Ford Health System
investigator full name: Benjamin Movsas, M.D.
investigator title: Chair, Department of Radiation Oncology
mesh term: Adenoviridae Infections
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No