<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/NCT01703754</url>
  </required_header>
  <id_info>
    <org_study_id>ATI001-201</org_study_id>
    <nct_id>NCT01703754</nct_id>
  </id_info>
  <brief_title>Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer.</brief_title>
  <official_title>A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alaunos Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alaunos Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with&#xD;
      accessible lesions.&#xD;
&#xD;
      Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time&#xD;
      point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with&#xD;
      chemotherapy (palifosfamide) is safe and efficacious.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter, open-label, randomized study evaluating the safety and efficacy of INXN-1001&#xD;
      (veledimex) and INXN-2001 (Ad-RTS-hIL-12) alone and in combination with palifosfamide.&#xD;
&#xD;
      Part 1 is the safety run-in where a safety assessment will be made after 1 cycle of therapy.&#xD;
&#xD;
      Part 2, eligible subjects will be randomly assigned to active treatment Arms A or C.&#xD;
&#xD;
      Once the monotherapy (Arm A) is determined to be safe and tolerable, Part 1 combination&#xD;
      therapy (Arm C) will begin.&#xD;
&#xD;
      Subjects should receive six cycles of study treatment, in the absence of meeting withdrawal&#xD;
      criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 2</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>Safety and tolerability of study drug therapy based on type and rate of adverse events and 16-week PFS rate.</measure>
    <time_frame>Approximately 24 weeks-Beginning from the time a patient signs the informed consent to the Follow up Tumor Assessment visit</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) by modified RECIST v1.1</measure>
    <time_frame>Approximately 24 weeks- From first study drug dose to Follow-Up Tumor Assessment Visit</time_frame>
    <description>Proportion of subjects achieving a confirmed PR or CR according to modified RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit rate: proportion of subjects with CR, PR, or SD by modified RECIST v1.1</measure>
    <time_frame>Approximately 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimate PFS by modified RECIST v1.1</measure>
    <time_frame>Approximately 24 weeks, beginning at the first study drug administratrion and ending at the Follow up Tumor Assessment visit</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate Pharmacodynamic tumor markers in tumor tissue samples that may correlate with objective tumor response and/or clinical outcome</measure>
    <time_frame>Approximately 24 weeks, starting with first study drug administrationa and ending at the Follow up Tumor Assessment visit</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Breast Cancer Nos Metastatic Recurrent</condition>
  <arm_group>
    <arm_group_label>Ad-RTS-hIL-12 and veledimex</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental study drug monotherapy arm (A)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ad-RTS-hIL-12 and Palifosfamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study drug combination therapy arm (C)</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Ad-RTS-hIL-12 and Veledimex</intervention_name>
    <description>Oral activator ligand with adenoviral vector injection of cancer lesions</description>
    <arm_group_label>Ad-RTS-hIL-12 and Palifosfamide</arm_group_label>
    <arm_group_label>Ad-RTS-hIL-12 and veledimex</arm_group_label>
    <other_name>Adenoviral Vector</other_name>
    <other_name>Oral activator ligand</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palifosfamide</intervention_name>
    <description>Small molecule chemotherapy, IV administration</description>
    <arm_group_label>Ad-RTS-hIL-12 and Palifosfamide</arm_group_label>
    <other_name>Pali</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Males or females ≥ 18 years of age&#xD;
&#xD;
          2. Histologically or cytologically confirmed adenocarcinoma of the breast, either locally&#xD;
             recurrent or metastatic disease with injectable lesions, for which no proven curative&#xD;
             therapy exists.&#xD;
&#xD;
          3. Failed or progressed on at least 1 prior systemic chemotherapy regimen ±&#xD;
             biologic/experimental therapy (if first-line therapy, failure or progression during&#xD;
             the first 30 days).&#xD;
&#xD;
          4. Resolution of all treatment-related toxicities to Grade 1 severity or lower, except&#xD;
             for stable sensory neuropathy ≤ Grade 2 and alopecia.&#xD;
&#xD;
          5. A minimum of 2 lesion(s) assessed by imaging using mRECIST v1.1.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group performance status 0, 1, 2&#xD;
&#xD;
          7. Male and female subjects must agree to use a highly reliable method of birth control.&#xD;
&#xD;
          8. Adequate bone marrow reserve as indicated by:&#xD;
&#xD;
               1. Absolute neutrophil count &gt; 1500/μL (without use of growth factors within 7 days)&#xD;
&#xD;
               2. Absolute lymphocyte count &gt; 700/μL (without use of growth factors within 7 days)&#xD;
&#xD;
               3. Platelet count &gt; 100,000/mm3 (without transfusion in prior 7 days)&#xD;
&#xD;
               4. Hemoglobin &gt; 9.0 g/dL (without transfusion in prior 7 days)&#xD;
&#xD;
          9. Estimated glomerular filtration rate using the Modification of Diet in Renal Disease&#xD;
             equation: eGFR ≥ 60 mL/min/1.73 m2&#xD;
&#xD;
         10. Adequate liver function as evidenced by the following:&#xD;
&#xD;
               1. Bilirubin ≤ 1.5 times the upper limits of normal (ULN)&#xD;
&#xD;
               2. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5×ULN,&#xD;
                  in the case of liver metastases ≤ 5×ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with human epidermal growth factor receptor 2 (HER2)/neu-positive&#xD;
             (immunohistochemistry [IHC]) 3+ or fluorescence in situ hybridization-amplified)&#xD;
             breast tumors who are eligible for, but who have not received HER2-targeted therapy&#xD;
             (eg, trastuzumab)&#xD;
&#xD;
          2. Concomitant anticancer therapies&#xD;
&#xD;
          3. Prior therapies discontinuation periods:&#xD;
&#xD;
               1. Radiation within 3 weeks of enrollment&#xD;
&#xD;
               2. Chemotherapy within 4 weeks of enrollment&#xD;
&#xD;
               3. Nitrosoureas within 6 weeks of enrollment&#xD;
&#xD;
               4. Biologic therapy and/or immunomodulatory therapy, checkpoint inhibitors within 6&#xD;
                  weeks of enrollment&#xD;
&#xD;
               5. No washout period is required for endocrine therapy&#xD;
&#xD;
          4. Radiation therapy encompassing &gt;25% of bone marrow&#xD;
&#xD;
          5. History of bone marrow or stem cell transplantation&#xD;
&#xD;
          6. Any congenital or acquired condition leading to inability to generate an immune&#xD;
             response&#xD;
&#xD;
          7. Immunosuppressive therapy:&#xD;
&#xD;
               1. Systemic immunosuppressive drugs including corticosteroids (prednisone equivalent&#xD;
                  &gt;10 mg/day)&#xD;
&#xD;
               2. Immune suppression/requiring immunosuppressive drugs, including organ allografts&#xD;
&#xD;
               3. Active autoimmune disease requiring the equivalent of &gt;10 mg/day of prednisone&#xD;
&#xD;
          8. Major surgery within 4 weeks of study treatment&#xD;
&#xD;
          9. History of prior malignancy, unless the prior malignancy was diagnosed and&#xD;
             definitively treated ≥5 years previously with no subsequent evidence of recurrence&#xD;
&#xD;
         10. Subjects with brain or subdural metastases, unless local therapy has completed and&#xD;
             corticosteroids have been discontinued for this indication for ≥4 weeks before&#xD;
             starting study treatment.&#xD;
&#xD;
         11. Any medications that induce, inhibit, or are substrates of cytochrome P450 (CYP450)&#xD;
             3A4 within 7 days prior to the first dose of study drug&#xD;
&#xD;
         12. Subjects with meningeal carcinomatosis&#xD;
&#xD;
         13. Known significant hypersensitivity to study drugs or excipients&#xD;
&#xD;
         14. History of malabsorption syndrome or other condition that would interfere with enteral&#xD;
             absorption&#xD;
&#xD;
         15. International Normalized Ratio (INR) and activated partial thromboplastin time [PTT]&#xD;
             &lt;1.5 x ULN, if not therapeutically anticoagulated.&#xD;
&#xD;
         16. New York Heart Association (NYHA) Class II or greater congestive heart failure OR&#xD;
             active ventricular arrhythmia requiring medication&#xD;
&#xD;
         17. Any other unstable or clinically significant concurrent medical condition&#xD;
&#xD;
         18. Localized infection at site of injectable lesion(s) requiring antiinfective therapy&#xD;
             within 2 weeks of the first dose of study drug.&#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>Francois Lebel, MD</last_name>
    <role>Study Director</role>
    <affiliation>Ziopharm Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Baptist Cancer Institute</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>
    <facility>
      <name>Billings Clinic</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Signal Point Clinical Research Center</name>
      <address>
        <city>Middletown</city>
        <state>Ohio</state>
        <zip>45042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Hospital System</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Jones Clinic, PC</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Medical Research Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evergreen Hematology &amp; Oncology</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>October 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>January 26, 2015</last_update_submitted>
  <last_update_submitted_qc>January 26, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 27, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Genetically Modified Organism</keyword>
  <keyword>Metastatic Breast Cancer</keyword>
  <keyword>Recurrent Breast Cancer</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>Palifosfamide</keyword>
  <keyword>INXN1001</keyword>
  <keyword>INXN2001</keyword>
  <keyword>Adenoviral vector</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Isophosphamide mustard</mesh_term>
    <mesh_term>Ifosfamide</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/NCT01703754
org study id: ATI001-201
nct id: NCT01703754
lead sponsor: 
has dmc: No
Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with
      accessible lesions.

      Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time
      point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with
      chemotherapy (palifosfamide) is safe and efficacious.
Multicenter, open-label, randomized study evaluating the safety and efficacy of INXN-1001
      (veledimex) and INXN-2001 (Ad-RTS-hIL-12) alone and in combination with palifosfamide.

      Part 1 is the safety run-in where a safety assessment will be made after 1 cycle of therapy.

      Part 2, eligible subjects will be randomly assigned to active treatment Arms A or C.

      Once the monotherapy (Arm A) is determined to be safe and tolerable, Part 1 combination
      therapy (Arm C) will begin.

      Subjects should receive six cycles of study treatment, in the absence of meeting withdrawal
      criteria.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of study drug therapy based on type and rate of adverse events and 16-week PFS rate.
time frame: Approximately 24 weeks-Beginning from the time a patient signs the informed consent to the Follow up Tumor Assessment visit
measure: Objective response rate (ORR) by modified RECIST v1.1
time frame: Approximately 24 weeks- From first study drug dose to Follow-Up Tumor Assessment Visit
description: Proportion of subjects achieving a confirmed PR or CR according to modified RECIST v1.1
measure: Clinical Benefit rate: proportion of subjects with CR, PR, or SD by modified RECIST v1.1
time frame: Approximately 24 weeks
measure: Estimate PFS by modified RECIST v1.1
time frame: Approximately 24 weeks, beginning at the first study drug administratrion and ending at the Follow up Tumor Assessment visit
measure: Evaluate Pharmacodynamic tumor markers in tumor tissue samples that may correlate with objective tumor response and/or clinical outcome
time frame: Approximately 24 weeks, starting with first study drug administrationa and ending at the Follow up Tumor Assessment visit
arm group label: Ad-RTS-hIL-12 and veledimex
arm group type: Experimental
description: Experimental study drug monotherapy arm (A)
arm group label: Ad-RTS-hIL-12 and Palifosfamide
arm group type: Experimental
description: Study drug combination therapy arm (C)
intervention type: Genetic
intervention name: Ad-RTS-hIL-12 and Veledimex
description: Oral activator ligand with adenoviral vector injection of cancer lesions
arm group label: Ad-RTS-hIL-12 and Palifosfamide
arm group label: Ad-RTS-hIL-12 and veledimex
other name: Adenoviral Vector
other name: Oral activator ligand
intervention type: Drug
intervention name: Palifosfamide
description: Small molecule chemotherapy, IV administration
arm group label: Ad-RTS-hIL-12 and Palifosfamide
other name: Pali
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Francois Lebel, MD
role: Study Director
affiliation: Ziopharm Oncology
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Recurrence
mesh term: Isophosphamide mustard
mesh term: Ifosfamide