<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/NCT03754933</url>
  </required_header>
  <id_info>
    <org_study_id>PNP-002</org_study_id>
    <secondary_id>R01FD005746-01A1</secondary_id>
    <secondary_id>14271</secondary_id>
    <nct_id>NCT03754933</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Repeat Administration of Ad/PNP and Fludarabine Phosphate in Patients With Local Head/Neck Cancer</brief_title>
  <official_title>Phase 1/2, Open-label Study Evaluating Safety of Repeat Administration of Ad/PNP-F-araAMP (Ad/PNP Administered Intratumorally Followed by Intravenous Fludarabine Phosphate) in Subjects With Recurrent, Local Head and Neck Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GeoVax, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>GeoVax, 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective: The primary objective of the study is to evaluate the safety of repeat&#xD;
      administration of a dose level of Ad/PNP plus fludarabine phosphate (F-araAMP) which&#xD;
      demonstrated anti-tumor activity in patients with advanced head and neck cancer in a&#xD;
      completed phase I study.&#xD;
&#xD;
      Secondary Objective: The secondary objective is to evaluate the antitumor activity of repeat&#xD;
      administration of Ad/PNP plus F-araAMP.&#xD;
&#xD;
      FDA Office of Orphan Drugs Division is a source of funding for the overall project.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Mechanism of action. The study drug, Ad/PNP-F-araAMP (Fludarabine phosphate) consists of&#xD;
           a nonreplicating adenoviral vector expressing the E. coli purine nucleoside&#xD;
           phosphorylase (PNP) injected intratumorally followed by intravenous administration of&#xD;
           F-araAMP. This combination generates 2-fluoroadenine (F-Ade) within the tumor resulting&#xD;
           in focal chemotherapeutic activity.&#xD;
&#xD;
           F-araAMP is an agent that is rapidly cleaved by plasma phosphatases to fludarabine,&#xD;
           which is the primary circulating form of the drug and has activity against certain&#xD;
           hematological malignancies, but not against solid tumors such as head and neck squamous&#xD;
           cell carcinoma (HNSCC). Fludarabine (F-araA) is an adenosine analog and substrate for E.&#xD;
           coli PNP, which cleaves the glycosidic bond of F-araA to generate F-Ade. The F-Ade&#xD;
           metabolite has shown pronounced activity against human tumor xenografts in mice.&#xD;
&#xD;
           Many refractory tumors are refractory precisely because they have a very low growth&#xD;
           fraction, i.e., a relatively small percentage of tumor cells dividing at any particular&#xD;
           point in time. In nonclinical studies, significant in vivo antitumor activity has been&#xD;
           demonstrated by F-Ade generation from F-araAMP in tumors in which 2.5 to 10% of cells&#xD;
           express the E. coli PNP gene. In addition, anti-tumor effect was seen in patients with&#xD;
           advanced solid tumors (melanoma and head and neck cancer) in the higher dose cohorts&#xD;
           during a Phase 1 study (see next section).&#xD;
&#xD;
        2. Tumor response with Ad/PNP-F-araAMP in Phase 1 Study. The safety and efficacy of&#xD;
           Ad/PNP-F-araAMP has been evaluated in a Phase 1 study, PNP-001. Four escalating dose&#xD;
           levels were evaluated in 10 subjects with head and neck cancer and 2 subjects with&#xD;
           melanoma; clinical activity was observed at the highest dose levels following 3&#xD;
           intratumoral injections of Ad/PNP over 2 days and IV F-araAMP phosphate over 3 days. The&#xD;
           overall response rate (CR+PR) was approximately 67% in the 2 highest dose cohorts,&#xD;
           Cohorts 3 and 4. Results suggest a dose response effect. The duration of response in the&#xD;
           injected tumor was limited, with 4 of 5 responding tumors having disease progression of&#xD;
           the injected lesion prior to last follow-up on Day 56, suggesting that repeat&#xD;
           administration should be evaluated. Ad/PNP + F-araAMP was well tolerated. No subject&#xD;
           experienced a dose-limiting toxicity and none of the subjects discontinued study&#xD;
           treatment. Overall, the activity and safety profile of Ad/PNP seen in the Phase 1 study&#xD;
           supports further clinical evaluation of repeat administration of Ad/PNP (IT) and&#xD;
           F-araAMP phosphate infusion for patients with HNSCC.&#xD;
&#xD;
        3. Purpose of the Study. Based upon the tumor response seen with a single administration of&#xD;
           the two highest dose levels of Ad/PNP-F-araAMP in the Phase 1 study, PNP plans to&#xD;
           investigate the safety and assess anti-tumor activity of repeat cycles of injection of&#xD;
           Ad/PNP + F-araAMP in patients with advanced head and neck cancer. Subjects in the study&#xD;
           will have RECIST 1.1 measurable HNSCC which is amenable to local injection for which&#xD;
           there is no effective curative or palliative treatment option. This study population was&#xD;
           selected since results from this Phase 1/2 trial are intended to support the safety of&#xD;
           repeat dosing in further clinical investigation.&#xD;
&#xD;
        4. Study Design. The trial is designed as a single-arm study to evaluate the safety of&#xD;
           repeat cycles of Ad/PNP and F-araAMP in patients with recurrent HNSCC with tumor(s)&#xD;
           accessible for injection. Ad/PNP will be injected intratumorally twice on Day 1 and once&#xD;
           on Day 2 followed by infusion of F-araAMP daily on Days 3, 4, and 5. Subjects will&#xD;
           receive repeat administration of Ad/PNP-F-araAMP every 4 weeks (i.e., each cycle) for 5&#xD;
           cycles or until injected tumor progresses, unacceptable toxicity occurs, no tumor is&#xD;
           present for injection, or patient death. Tumor response in the injected tumor(s) will be&#xD;
           assessed by physical examination as well as by radiographic imaging. All subjects will&#xD;
           be monitored for adverse events during study participation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 11, 2019</start_date>
  <completion_date type="Anticipated">August 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2024</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 as measured by the number of adverse events Grade 2 and above that are considered by investigator to be definitely, probably, or possibly related to study treatment, graded according to Common Terminology Criteria for Adverse Effects v. 4.0</measure>
    <time_frame>up to 60 days</time_frame>
    <description>Adverse events Grade 2 and above that are considered by investigator to be definitely, probably, or possibly related to study treatment will be collected from initial dose through 60 days after last dose of study drug. Outcome measure will be reported as the number of events for each dose group, and all safety events will be summarized with descriptive statistics.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (ORR) per RECIST 1.1.</measure>
    <time_frame>Six months</time_frame>
    <description>Best durable overall response (ORR) defined as CR or partial response determined by RECIST 1.1 persisting for at least 4 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Six months</time_frame>
    <description>Progression Free Survival (PFS) defined as time from first intratrumoral injection to date of progression or to death, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of treatment response</measure>
    <time_frame>Six months</time_frame>
    <description>Duration of treatment response defined as time from first documentation of CR or PR until first occurrence of disease progression or death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Recurrent Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>Ad/PNP + fludarabine phosphate, 5 cycles</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ad/PNP</intervention_name>
    <description>Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase</description>
    <arm_group_label>Ad/PNP + fludarabine phosphate, 5 cycles</arm_group_label>
    <other_name>Gedeptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Fludarabine phosphate is an anticancer agent currently used to treatment patients with chronic lymphocytic leukemia.</description>
    <arm_group_label>Ad/PNP + fludarabine phosphate, 5 cycles</arm_group_label>
    <other_name>Fludara</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provided Informed Consent&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Patients with histologically or cytologically confirmed diagnosis of recurrent cancer&#xD;
             of the head and neck region for whom there is no curative treatment option. For the&#xD;
             purposes of trial eligibility, cancers of the head and neck shall include, in addition&#xD;
             to head and neck squamous cell carcinoma (HNSCC), cutaneous squamous cell primary&#xD;
             sites and squamous cell carcinoma of unknown primary presenting with neck lymph nodal&#xD;
             disease, as well as nasopharyngeal carcinoma, and salivary gland tumors.&#xD;
&#xD;
          4. All standard or approved treatment options that would provide substantive palliation&#xD;
             must have failed, been exhausted, or patient not eligible or willing to use them (for&#xD;
             example neuropathy, nephropathy , or hearing loss precluding the use of cisplatin)&#xD;
&#xD;
          5. Tumor mass (primary tumor and/or lymphadenopathy) measurable by Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) 1.1 and technically suitable for intratumoral&#xD;
             injections (otolaryngologist will determine feasibility). Patients with nodal disease&#xD;
             (or metastatic disease) that is needle accessible are eligible. Patients with&#xD;
             additional tumors (including distant metastatic disease) beyond the intratumoral&#xD;
             injection accessible tumor(s) that are not accessible for intratumoral injection are&#xD;
             eligible ONLY if the patient has no other treatment option for the metastatic disease&#xD;
             and treatment of local disease may provide the patient some benefit or palliation.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group performance status of ≤ 2&#xD;
&#xD;
          7. In the judgment of the Investigator, the patient has recovered sufficiently from any&#xD;
             previous significant therapy side effects or toxicities prior to Ad/PNP&#xD;
             administration.&#xD;
&#xD;
          8. Absolute neutrophil count ≥ 1,500 cells/ul; hemoglobin ≥ 9 g/dl, platelets ≥&#xD;
             100,000/ul&#xD;
&#xD;
          9. Serum creatinine ≤ 1.5 mg/dl, or calculated creatinine clearance ≥ 60 ml/min&#xD;
&#xD;
         10. Bilirubin ≤ upper limit of normal, alanine aminotransferase ≤ 1.5 x upper limit of&#xD;
             normal and/or aspartate aminotransferase ≤ 1.5 x upper limit of normal, alkaline&#xD;
             phosphatase ≤ 2.5 x upper limit of normal&#xD;
&#xD;
         11. Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 x upper limit of&#xD;
             normal&#xD;
&#xD;
         12. Activated partial thromboplastin (aPTT) time ≤ 1.5 x upper limit of normal&#xD;
&#xD;
         13. Female patients must have a negative urine or serum pregnancy at screening (pregnancy&#xD;
             test is not required for patients with bilateral oophorectomy and/or hysterectomy or&#xD;
             for those patients who are &gt; 1 year postmenopausal)&#xD;
&#xD;
         14. All patients of reproductive potential must agree to use a medically acceptable form&#xD;
             of contraception (eg, hormonal birth control, double-barrier method) or abstinence.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior history or current diagnosis of leukemia&#xD;
&#xD;
          2. Have received any gene therapy products or oncolytic viral therapy&#xD;
&#xD;
          3. Receiving allopurinol&#xD;
&#xD;
          4. Received an investigational drug within 30 days prior to first injection of Ad/PNP&#xD;
&#xD;
          5. Received radiation treatment &lt; 4 weeks prior to first injection of Ad/PNP, and does&#xD;
             not have any RECIST 1.1 evaluable lesions that are outside the radiation field. (If&#xD;
             the patient has RECIST 1.1 evaluable lesions outside the radiation field then they can&#xD;
             be included.)&#xD;
&#xD;
          6. Received chemotherapy (systemic anticancer treatment) &lt; 4 weeks prior to first&#xD;
             injection of Ad/PNP and has not recovered from all the related side effects. (If the&#xD;
             patient has recovered from all related side effects or has reached a new baseline,&#xD;
             then they may begin receiving treatment at sooner than 4 weeks)&#xD;
&#xD;
          7. Have significant baseline neuropathy (&gt; Grade 2 based on Common Terminology Criteria&#xD;
             for Adverse events [CTCAE] v5.0)&#xD;
&#xD;
          8. Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease,&#xD;
             active infection)&#xD;
&#xD;
          9. Had within 6 months prior to enrollment: Myocardial infarction, cerebral vascular&#xD;
             accident, uncontrolled congestive heart failure, significant liver disease, unstable&#xD;
             angina&#xD;
&#xD;
         10. Fever (temperature &gt; 38.1 degrees C orally)&#xD;
&#xD;
         11. Receiving chronic systemic corticosteroids (&gt; 3 weeks) or any chronic&#xD;
             immunosuppressive medications within 14 days prior to first injection of Ad/PNP.&#xD;
             Subjects receiving short courses of corticosteroids are considered eligible for the&#xD;
             study.&#xD;
&#xD;
         12. Receiving anticoagulants other than those to maintain patency of venous lines&#xD;
&#xD;
         13. Women who are pregnant or breast feeding&#xD;
&#xD;
         14. History of HIV infection. No requirement for testing.&#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>A. Dimitrios Colevas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chief Medical Officer</last_name>
    <phone>678-384-7220</phone>
    <email>info@geovax.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Director Clinical Operations</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luis Martinez Ramirez</last_name>
      <phone>650-736-2344</phone>
      <email>martluis@stanford.edu</email>
    </contact>
    <contact_backup>
      <last_name>A. Dimitrios Colevas, MD</last_name>
      <phone>650-724-9707</phone>
      <email>colevas@stanford.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute - Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Madison Miller Stallings</last_name>
      <phone>404-686-1794</phone>
      <email>madison.miller.stallings@emory.edu</email>
    </contact>
    <contact_backup>
      <last_name>Nicole C. Schmitt, MD, FACS</last_name>
      <phone>404-778-1900</phone>
      <email>nicole.cherie.schmitt@emory.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Camilo Henao, MPH</last_name>
      <phone>215-955-9959</phone>
      <email>Camilo.Henao@jefferson.edu</email>
    </contact>
    <contact_backup>
      <last_name>Joseph M Curry, MD, FACS</last_name>
      <phone>215-955-6760</phone>
      <email>joseph.curry@jefferson.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Parker WB, Sorscher EJ. Use of E. coli Purine Nucleoside Phosphorylase in the Treatment of Solid Tumors. Curr Pharm Des. 2017 Nov 8:10.2174/1381612823666171109101851. doi: 10.2174/1381612823666171109101851. Online ahead of print.</citation>
    <PMID>29119917</PMID>
  </reference>
  <reference>
    <citation>Rosenthal EL, Chung TK, Parker WB, Allan PW, Clemons L, Lowman D, Hong J, Hunt FR, Richman J, Conry RM, Mannion K, Carroll WR, Nabell L, Sorscher EJ. Phase I dose-escalating trial of Escherichia coli purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors. Ann Oncol. 2015 Jul;26(7):1481-7. doi: 10.1093/annonc/mdv196. Epub 2015 Apr 21.</citation>
    <PMID>25899782</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>October 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fludarabine</keyword>
  <keyword>Adenovirus</keyword>
  <keyword>Head &amp; neck squamous cell carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
  </intervention_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/NCT03754933
org study id: PNP-002
secondary id: R01FD005746-01A1
secondary id: 14271
nct id: NCT03754933
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Primary Objective: The primary objective of the study is to evaluate the safety of repeat
      administration of a dose level of Ad/PNP plus fludarabine phosphate (F-araAMP) which
      demonstrated anti-tumor activity in patients with advanced head and neck cancer in a
      completed phase I study.

      Secondary Objective: The secondary objective is to evaluate the antitumor activity of repeat
      administration of Ad/PNP plus F-araAMP.

      FDA Office of Orphan Drugs Division is a source of funding for the overall project.
1. Mechanism of action. The study drug, Ad/PNP-F-araAMP (Fludarabine phosphate) consists of
           a nonreplicating adenoviral vector expressing the E. coli purine nucleoside
           phosphorylase (PNP) injected intratumorally followed by intravenous administration of
           F-araAMP. This combination generates 2-fluoroadenine (F-Ade) within the tumor resulting
           in focal chemotherapeutic activity.

           F-araAMP is an agent that is rapidly cleaved by plasma phosphatases to fludarabine,
           which is the primary circulating form of the drug and has activity against certain
           hematological malignancies, but not against solid tumors such as head and neck squamous
           cell carcinoma (HNSCC). Fludarabine (F-araA) is an adenosine analog and substrate for E.
           coli PNP, which cleaves the glycosidic bond of F-araA to generate F-Ade. The F-Ade
           metabolite has shown pronounced activity against human tumor xenografts in mice.

           Many refractory tumors are refractory precisely because they have a very low growth
           fraction, i.e., a relatively small percentage of tumor cells dividing at any particular
           point in time. In nonclinical studies, significant in vivo antitumor activity has been
           demonstrated by F-Ade generation from F-araAMP in tumors in which 2.5 to 10% of cells
           express the E. coli PNP gene. In addition, anti-tumor effect was seen in patients with
           advanced solid tumors (melanoma and head and neck cancer) in the higher dose cohorts
           during a Phase 1 study (see next section).

        2. Tumor response with Ad/PNP-F-araAMP in Phase 1 Study. The safety and efficacy of
           Ad/PNP-F-araAMP has been evaluated in a Phase 1 study, PNP-001. Four escalating dose
           levels were evaluated in 10 subjects with head and neck cancer and 2 subjects with
           melanoma; clinical activity was observed at the highest dose levels following 3
           intratumoral injections of Ad/PNP over 2 days and IV F-araAMP phosphate over 3 days. The
           overall response rate (CR+PR) was approximately 67% in the 2 highest dose cohorts,
           Cohorts 3 and 4. Results suggest a dose response effect. The duration of response in the
           injected tumor was limited, with 4 of 5 responding tumors having disease progression of
           the injected lesion prior to last follow-up on Day 56, suggesting that repeat
           administration should be evaluated. Ad/PNP + F-araAMP was well tolerated. No subject
           experienced a dose-limiting toxicity and none of the subjects discontinued study
           treatment. Overall, the activity and safety profile of Ad/PNP seen in the Phase 1 study
           supports further clinical evaluation of repeat administration of Ad/PNP (IT) and
           F-araAMP phosphate infusion for patients with HNSCC.

        3. Purpose of the Study. Based upon the tumor response seen with a single administration of
           the two highest dose levels of Ad/PNP-F-araAMP in the Phase 1 study, PNP plans to
           investigate the safety and assess anti-tumor activity of repeat cycles of injection of
           Ad/PNP + F-araAMP in patients with advanced head and neck cancer. Subjects in the study
           will have RECIST 1.1 measurable HNSCC which is amenable to local injection for which
           there is no effective curative or palliative treatment option. This study population was
           selected since results from this Phase 1/2 trial are intended to support the safety of
           repeat dosing in further clinical investigation.

        4. Study Design. The trial is designed as a single-arm study to evaluate the safety of
           repeat cycles of Ad/PNP and F-araAMP in patients with recurrent HNSCC with tumor(s)
           accessible for injection. Ad/PNP will be injected intratumorally twice on Day 1 and once
           on Day 2 followed by infusion of F-araAMP daily on Days 3, 4, and 5. Subjects will
           receive repeat administration of Ad/PNP-F-araAMP every 4 weeks (i.e., each cycle) for 5
           cycles or until injected tumor progresses, unacceptable toxicity occurs, no tumor is
           present for injection, or patient death. Tumor response in the injected tumor(s) will be
           assessed by physical examination as well as by radiographic imaging. All subjects will
           be monitored for adverse events during study participation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety as measured by the number of adverse events Grade 2 and above that are considered by investigator to be definitely, probably, or possibly related to study treatment, graded according to Common Terminology Criteria for Adverse Effects v. 4.0
time frame: up to 60 days
description: Adverse events Grade 2 and above that are considered by investigator to be definitely, probably, or possibly related to study treatment will be collected from initial dose through 60 days after last dose of study drug. Outcome measure will be reported as the number of events for each dose group, and all safety events will be summarized with descriptive statistics.
measure: Best Overall Response (ORR) per RECIST 1.1.
time frame: Six months
description: Best durable overall response (ORR) defined as CR or partial response determined by RECIST 1.1 persisting for at least 4 weeks
measure: Progression Free Survival (PFS)
time frame: Six months
description: Progression Free Survival (PFS) defined as time from first intratrumoral injection to date of progression or to death, whichever occurs first.
measure: Duration of treatment response
time frame: Six months
description: Duration of treatment response defined as time from first documentation of CR or PR until first occurrence of disease progression or death.
arm group label: Ad/PNP + fludarabine phosphate, 5 cycles
arm group type: Experimental
intervention type: Biological
intervention name: Ad/PNP
description: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase
arm group label: Ad/PNP + fludarabine phosphate, 5 cycles
other name: Gedeptin
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Fludarabine phosphate is an anticancer agent currently used to treatment patients with chronic lymphocytic leukemia.
arm group label: Ad/PNP + fludarabine phosphate, 5 cycles
other name: Fludara
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: A. Dimitrios Colevas, MD
role: Principal Investigator
affiliation: Stanford University
last name: Chief Medical Officer
phone: 678-384-7220
email: info@geovax.com
last name: Director Clinical Operations
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Parker WB, Sorscher EJ. Use of E. coli Purine Nucleoside Phosphorylase in the Treatment of Solid Tumors. Curr Pharm Des. 2017 Nov 8:10.2174/1381612823666171109101851. doi: 10.2174/1381612823666171109101851. Online ahead of print.
PMID: 29119917
citation: Rosenthal EL, Chung TK, Parker WB, Allan PW, Clemons L, Lowman D, Hong J, Hunt FR, Richman J, Conry RM, Mannion K, Carroll WR, Nabell L, Sorscher EJ. Phase I dose-escalating trial of Escherichia coli purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors. Ann Oncol. 2015 Jul;26(7):1481-7. doi: 10.1093/annonc/mdv196. Epub 2015 Apr 21.
PMID: 25899782
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
mesh term: Fludarabine
mesh term: Fludarabine phosphate
sharing ipd: No