<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/NCT01664273</url>
  </required_header>
  <id_info>
    <org_study_id>AA 1201</org_study_id>
    <nct_id>NCT01664273</nct_id>
  </id_info>
  <brief_title>Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer</brief_title>
  <official_title>Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Copenhagen University Hospital at Herlev</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Copenhagen University Hospital at Herlev</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gene transfer by electroporation (gene electrotransfer) uses short electric pulses to&#xD;
      transiently permeabilise the cell membrane enabling passage of plasmid DNA into the cell&#xD;
      cytosol. It is an efficient non-viral method for gene delivery to various tissues. In this&#xD;
      phase I dose-escalating study, patients will be treated with intramuscular gene&#xD;
      electrotransfer of plasmid AMEP. Plasmid AMEP encodes protein AMEP which bind to α5β1 og αvβ3&#xD;
      integrins. Primary end point of the trial is safety and secondary end points are efficacy,&#xD;
      pharmacokinetics and evaluation of potential discomfort associated with the treatment&#xD;
      procedure using VAS (Visual Analogue Scale).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cohorts of 3 patients will be treated with increasing doses of plasmid AMEP. Up to 12&#xD;
      patients will be treated.&#xD;
&#xD;
      Treatment procedure: Local anesthetic is applied to m. quadriceps femoris (thigh muscle) and&#xD;
      the skin. An incision of the skin is performed followed by dissection until the muscle is&#xD;
      exposed. The surgical procedure is performed by plastic surgeons.&#xD;
&#xD;
      Plasmid AMEP is injected intramuscularly and immediately followed by application of electric&#xD;
      pulses via a needle electrode inserted into the muscle. A combination of one high voltage&#xD;
      pulse (700V/cm, 100 µs) followed by one low voltage pulse (80 V/cm, 400 ms) will be applied.&#xD;
      The wound is sutured and a dressing is applied. Treatment procedure is estimated to 30&#xD;
      minutes.&#xD;
&#xD;
      All patients are hospitalized for 24 hours after treatment for the purpose of evaluation of&#xD;
      vital signs, physical examination, AE and SAE recording and pharmacokinetics sampling (blood&#xD;
      and urine).&#xD;
&#xD;
      Blood biochemistry including LDH and CK is taken 24 hours post treatment. ECG will be taken&#xD;
      before and after treatment. Patients score discomfort or pain from treated area using VAS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Production of the IMP (plasmid AMEP) has been terminated by the supplier (BioAlliance Pharma)&#xD;
  </why_stopped>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">May 2015</completion_date>
  <primary_completion_date type="Anticipated">May 2015</primary_completion_date>
  <phase>Phase 1</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 of the trial treatment</measure>
    <time_frame>From treatment to last follow up, planned 8 weeks.</time_frame>
    <description>Safety is evaluated by registration of adverse events (Adverse Events and Serious Adverse Events) using the CTCAE criteria version 4.0. Patients are seen in the out patient clinic once a week during the first month after treatment (at day 8, day 15, day 22, day 29) and 8 weeks after treatment. If no progression of the disease at 8 weeks, patients are seen at 12 weeks and then every three months until disease progression or death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy of the trial treatment</measure>
    <time_frame>PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.</time_frame>
    <description>PET/CT scan will be evaluated using RECIST 1.1 (CT) and PERCIST (PET)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.</time_frame>
    <description>Measurements of plasma and urine plasmid AMEP concentrations. Measurements of plasma and urine protein AMEP concentrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Discomfort associated with the treatment procedure</measure>
    <time_frame>Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.</time_frame>
    <description>The patient completes VAS (Visual Analogue Scale) scores pain related to the treatment area at abovementioned time points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>Day after treatment and 14 days after treatment</time_frame>
    <description>MR scan of treated region (thigh muscle) in order to assess potential intramuscular edema or hematoma</description>
  </secondary_outcome>
  <enrollment type="Actual">7</enrollment>
  <condition>Metastatic Malignant Neoplasm</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Plasmid AMEP</intervention_name>
    <description>Cohorts of 3 patients will received increasing doses of plasmid AMEP:&#xD;
50 μg, 100 μg, 250 μg and 500 μg. Starting dose will be the lowest dose.&#xD;
Injection volume will remain constant at 200 μL.&#xD;
Once-only treatment and intra-individual dose escalation will therefore not occur.</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years.&#xD;
&#xD;
          -  Performance status &lt; 1 (ECOG).&#xD;
&#xD;
          -  Histologically confirmed malignant tumor (solid tumor) of any histology,&#xD;
&#xD;
          -  Metastatic disease. Patients with asymptomatic brain metastases are eligible.&#xD;
&#xD;
          -  Patient should have been offered standard treatment. Patient is eligible if no&#xD;
             standard treatment is available or if the patient does not wish to receive standard&#xD;
             treatment.&#xD;
&#xD;
          -  Life expectancy ≥ 3 months.&#xD;
&#xD;
          -  Measurable disease defined as at least one measurable lesion according to RECIST 1.1&#xD;
&#xD;
          -  Patient should have adequate organ function:&#xD;
&#xD;
          -  Adequate bone marrow function: Neutrophil count ≥ 1.0 x 109/l (≤ grade 2 CTCAE 4.0);&#xD;
             Platelet count ≥ 75 x 109/l (&lt; grade 2 CTCAE 4.0); Hemoglobin ≥ 6,0 mmol/l.&#xD;
&#xD;
          -  Liver: ALAT or ASAT &lt; 3 ULN (&lt; grade 2 CTCAE 4.0); Bilirubin ≤ 1,5 ULN (&lt; grade 2&#xD;
             CTCAE 4.0); APTT within normal range; INR ≤ 1,2 (&lt; grade 1 CTCAE 4.0)&#xD;
&#xD;
          -  Kidney: Plasma creatinin ≤ 1.5 ULN (&lt; grade 2 CTCAE 4.0)&#xD;
&#xD;
          -  At least 4 weeks since any anti-cancer treatment.&#xD;
&#xD;
          -  Men and women of reproductive age must use effective contraception during the study&#xD;
             and at least 6 months after administration of plasmid AMEP.&#xD;
&#xD;
          -  Patient should be able to understand the participant information and able to comply&#xD;
             with protocol requirements and scheduled visits.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to the anaesthetic used.&#xD;
&#xD;
          -  Clinical signs of active infection.&#xD;
&#xD;
          -  Implanted pacemaker, defibrillator or any other implanted electronic device.&#xD;
&#xD;
          -  Participation in other clinical trials involving experimental drugs or participation&#xD;
             in a clinical trial within 4 weeks before initiation of study treatment.&#xD;
&#xD;
          -  AMI (acute myocardial infarction), stroke or acute ischemic event within the last 6&#xD;
             months.&#xD;
&#xD;
          -  Severe atherosclerosis, significant cardiovascular disease (NYHA III or IV) or&#xD;
             significant arrhythmias.&#xD;
&#xD;
          -  Systolic blood pressure above 180 mm Hg and/or diastolic blood pressure above 110 mm&#xD;
             Hg. If BP &gt;180/110 mm Hg medical correction is allowed and the patient can be included&#xD;
             when BP &lt; 180/110 mm Hg.&#xD;
&#xD;
          -  Pregnancy and lactation.&#xD;
&#xD;
          -  Clinically significant coagulopathy.&#xD;
&#xD;
          -  Treatment with anticoagulant drugs.&#xD;
&#xD;
          -  Other disorders which the investigator finds incompatible with participation in the&#xD;
             study.&#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>Julie Gehl, MD DMSci</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Oncology, Copenhagen University Hospital Herlev</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Depart. of Oncology, Copenhagen Universtiy Hospital Herlev</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>July 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <last_update_submitted>June 19, 2014</last_update_submitted>
  <last_update_submitted_qc>June 19, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 20, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>electroporation</keyword>
  <keyword>gen electrotransfer</keyword>
  <keyword>muscle</keyword>
  <keyword>plasmid AMEP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT01664273
org study id: AA 1201
nct id: NCT01664273
lead sponsor: 
has dmc: Yes
Gene transfer by electroporation (gene electrotransfer) uses short electric pulses to
      transiently permeabilise the cell membrane enabling passage of plasmid DNA into the cell
      cytosol. It is an efficient non-viral method for gene delivery to various tissues. In this
      phase I dose-escalating study, patients will be treated with intramuscular gene
      electrotransfer of plasmid AMEP. Plasmid AMEP encodes protein AMEP which bind to α5β1 og αvβ3
      integrins. Primary end point of the trial is safety and secondary end points are efficacy,
      pharmacokinetics and evaluation of potential discomfort associated with the treatment
      procedure using VAS (Visual Analogue Scale).
Cohorts of 3 patients will be treated with increasing doses of plasmid AMEP. Up to 12
      patients will be treated.

      Treatment procedure: Local anesthetic is applied to m. quadriceps femoris (thigh muscle) and
      the skin. An incision of the skin is performed followed by dissection until the muscle is
      exposed. The surgical procedure is performed by plastic surgeons.

      Plasmid AMEP is injected intramuscularly and immediately followed by application of electric
      pulses via a needle electrode inserted into the muscle. A combination of one high voltage
      pulse (700V/cm, 100 µs) followed by one low voltage pulse (80 V/cm, 400 ms) will be applied.
      The wound is sutured and a dressing is applied. Treatment procedure is estimated to 30
      minutes.

      All patients are hospitalized for 24 hours after treatment for the purpose of evaluation of
      vital signs, physical examination, AE and SAE recording and pharmacokinetics sampling (blood
      and urine).

      Blood biochemistry including LDH and CK is taken 24 hours post treatment. ECG will be taken
      before and after treatment. Patients score discomfort or pain from treated area using VAS.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of the trial treatment
time frame: From treatment to last follow up, planned 8 weeks.
description: Safety is evaluated by registration of adverse events (Adverse Events and Serious Adverse Events) using the CTCAE criteria version 4.0. Patients are seen in the out patient clinic once a week during the first month after treatment (at day 8, day 15, day 22, day 29) and 8 weeks after treatment. If no progression of the disease at 8 weeks, patients are seen at 12 weeks and then every three months until disease progression or death.
measure: Efficacy of the trial treatment
time frame: PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.
description: PET/CT scan will be evaluated using RECIST 1.1 (CT) and PERCIST (PET)
measure: Pharmacokinetics
time frame: Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.
description: Measurements of plasma and urine plasmid AMEP concentrations. Measurements of plasma and urine protein AMEP concentrations
measure: Discomfort associated with the treatment procedure
time frame: Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.
description: The patient completes VAS (Visual Analogue Scale) scores pain related to the treatment area at abovementioned time points.
measure: Safety
time frame: Day after treatment and 14 days after treatment
description: MR scan of treated region (thigh muscle) in order to assess potential intramuscular edema or hematoma
intervention type: Drug
intervention name: Plasmid AMEP
description: Cohorts of 3 patients will received increasing doses of plasmid AMEP:
50 μg, 100 μg, 250 μg and 500 μg. Starting dose will be the lowest dose.
Injection volume will remain constant at 200 μL.
Once-only treatment and intra-individual dose escalation will therefore not occur.
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Julie Gehl, MD DMSci
role: Principal Investigator
affiliation: Department of Oncology, Copenhagen University Hospital Herlev
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Neoplasms