<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/NCT03040180</url>
  </required_header>
  <id_info>
    <org_study_id>REG-32-2016</org_study_id>
    <nct_id>NCT03040180</nct_id>
  </id_info>
  <brief_title>Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer</brief_title>
  <acronym>nECT</acronym>
  <official_title>Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized Clinical Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zealand University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Herlev Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Zealand University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of neoadjuvant&#xD;
      electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative&#xD;
      clinical setting, using an endoscopic electroporation device (EndoVE).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Electroporation of cancer cells allows for a greater concentration of chemotherapy drugs to&#xD;
      enter the tumor cells. The uptake of the chemotherapeutic drug is aided through the&#xD;
      application of short electric pulses to the tumor mass (referred to as - Electrochemotherapy&#xD;
      or ECT). The pulses make the tumor cells more porous which allows the drug easier access into&#xD;
      the cancer cells, whereas other tissues and organs in the body remain relatively poor at&#xD;
      absorbing the drug, thereby reducing the potential side effects on healthy tissues.&#xD;
      Procedures with electrochemotherapy have previously been applied to human patients in other&#xD;
      countries of the EU, the US and Japan.&#xD;
&#xD;
      The drug concentration used is significantly reduced due to the more targeted absorption by&#xD;
      the tumor and this significantly reduces side effects normally associated with chemotherapy.&#xD;
&#xD;
      A large number of preclinical and clinical Phase I and I/II studies have demonstrated the&#xD;
      efficiency and safety of ECT. These studies have included patients with melanoma, head and&#xD;
      neck squamous cell carcinoma, merkel cell carcinomas, basal cell carcinoma and adenocarcinoma&#xD;
      nodules.&#xD;
&#xD;
      An endoscopic system (EndoVE ) for delivering the electric pulses to gastrointestinal tumors&#xD;
      has recently been developed. The treatment procedure is similar to standard endoscopic&#xD;
      colorectal examination (therapeutic colonoscopy) with the added element of an intravenous&#xD;
      injection of bleomycin followed by the delivery of electric pulses (each one less than 1msec&#xD;
      in duration). The pulses are endoscopically delivered directly to the tumor mass. The entire&#xD;
      procedure is minimally invasive and completely ambulatory. A successful treatment will cause&#xD;
      the tumor to shrink in size in the weeks following the procedure.&#xD;
&#xD;
      The objective of this study is to investigate the efficacy and safety of this approach in&#xD;
      downsizing locally advanced rectal tumors prior to intended curative surgery.&#xD;
&#xD;
      Time frame:&#xD;
&#xD;
        1. All patients will be treated with standard neoadjuvant chemoradiation therapy prior to&#xD;
           enrollment in this trial.&#xD;
&#xD;
        2. Alle patients will have PET/MRI scans performed twice to evaluate treatment response&#xD;
           (before and after ECT)&#xD;
&#xD;
        3. ECT treatment will be performed 4 weeks prior to surgery outlined by MDT.&#xD;
&#xD;
        4. Alle patients will be followed up for 3 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Anticipated">September 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Histopathologic tumor regression following electrochemotherapy</measure>
    <time_frame>4 weeks</time_frame>
    <description>Number of participants with histopathologic tumor regression following elctrochemotherapy as assesed by histopathological evaluation of Tumor Regression Grade (Mandard Classification, TRG 1-5)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment safety of electrochemotherapy</measure>
    <time_frame>4 months</time_frame>
    <description>Number of participants with treatment-related adverse events as assesed by CTCAE version 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment safety of surgery following electrochemotherapy</measure>
    <time_frame>4 weeks</time_frame>
    <description>Number of participants with compromized surgery following electrochemotherapy assesed by R1 resection rate, CRM involvement, non-mesorectal resection plane, and post operative complications according to Clavien-Dindo Classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor regression according to Hybrid PET/MRI following electrochemotherapy</measure>
    <time_frame>4 weeks</time_frame>
    <description>Tumor regression as assesed by tumor stage (T-stage)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Immunologic response following electrochemotherapy</measure>
    <time_frame>4 weeks</time_frame>
    <description>Tumor immunologic infiltration as assesed by the Immunoscore through immunohistochemical analysis</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Locally Advanced Rectal Cancer</condition>
  <condition>Electrochemotherapy</condition>
  <condition>Neoadjuvant Therapy</condition>
  <condition>Down Staging</condition>
  <arm_group>
    <arm_group_label>Electrochemotherapy with bleomycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Systemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA.&#xD;
BSA by Du Bois formula.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Electrochemotherapy with bleomycin</intervention_name>
    <description>Systemic injection, once only treatment</description>
    <arm_group_label>Electrochemotherapy with bleomycin</arm_group_label>
    <other_name>ATC code L01DC01</other_name>
    <other_name>EV substance code SUB00844MIG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>EndoVE</intervention_name>
    <description>Electroporation using an endoscopic electroporation device</description>
    <arm_group_label>Electrochemotherapy with bleomycin</arm_group_label>
    <other_name>Endoscopic electroporation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient must be mentally capable of understanding the information given.&#xD;
&#xD;
          2. Patients must give written informed consent.&#xD;
&#xD;
          3. Men or women aged at least 18 years.&#xD;
&#xD;
          4. Histologically verified rectal tumor (adenocarcinoma)&#xD;
&#xD;
          5. Case reviewed by MDT (surgery, radiology, oncology). Case considered curable with&#xD;
             neoadjuvant therapy followed by surgical excision (UICC stadium II-III).&#xD;
&#xD;
          6. ASA class I-III (Classification of the American Society of Anesthesiology)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Coagulation disorders&#xD;
&#xD;
          2. Highly inflamed gastrointestinal tissue which is ulcerated and bleeding&#xD;
&#xD;
          3. Patients with ICD or pacemaker units.&#xD;
&#xD;
          4. Patients with epilepsy.&#xD;
&#xD;
          5. Pregnancy or lactation/breastfeeding.&#xD;
&#xD;
          6. Patients with known Hepatitis B/C or HIV infection.&#xD;
&#xD;
          7. Patients who have undergone treatment with bevacizumab within 4 weeks prior to&#xD;
             enrolment in this trial.&#xD;
&#xD;
          8. Patients with concomitant use of phenytoin.&#xD;
&#xD;
          9. Patients with concomitant use of clozapine.&#xD;
&#xD;
         10. Concurrent treatment with an investigational medicinal product.&#xD;
&#xD;
         11. Patients with any other clinical condition or prior therapy that, in the opinion of&#xD;
             the investigator, would make the patient unsuitable for the study or unable to comply&#xD;
             with the study recruitments.&#xD;
&#xD;
         12. Patients with contraindications for PET/MRI scan:&#xD;
&#xD;
         13. Advanced tumor stage, UICC stage IV.&#xD;
&#xD;
         14. Acute pulmonary infection.&#xD;
&#xD;
         15. Medical history of severe pulmonary disease.&#xD;
&#xD;
         16. Previous allergic reactions to bleomycin.&#xD;
&#xD;
         17. Previous cumulative dose of bleomycin exceeding 250.000 IU/m2.&#xD;
&#xD;
         18. Pre-existing renal dysfunction. Creatinine clearance &lt; 40 ml/min.&#xD;
&#xD;
         19. Platelet count ≤50 mia/l.&#xD;
&#xD;
         20. Prothrombin time ≥ 40 sec&#xD;
&#xD;
         21. Patients registered in the Danish Tissue Register (Vaevsanvendelsesregistret)&#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>Ismail Gögenur, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Surgery, Zealand University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julie Gehl, MD, DMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of oncology, herlev Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ismail Gögenur, MD, DMSc</last_name>
    <phone>+45 26336426</phone>
    <email>igo@regionsjaelland.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rasmus P Vogelsang, MD</last_name>
    <phone>+45 27351103</phone>
    <email>rvo@regionsjaelland.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Oncology</name>
      <address>
        <city>Herlev</city>
        <state>Capitol Region</state>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julie Gehl, MD, DMSc</last_name>
      <phone>+45 38683868</phone>
      <email>karen.julie.gehl@regionh.dk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Department of Surgery</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ismail Gögenur, MD, DMSc</last_name>
      <phone>+45 26336426</phone>
      <email>igo@regionsjaelland.dk</email>
    </contact>
    <contact_backup>
      <last_name>Rasmus P Vogelsang, MD</last_name>
      <phone>+45 27351103</phone>
    </contact_backup>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>January 24, 2019</last_update_submitted>
  <last_update_submitted_qc>January 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neoplasms</keyword>
  <keyword>Neoplasms, primary</keyword>
  <keyword>Cancer</keyword>
  <keyword>Colorectal cancer</keyword>
  <keyword>rectal cancer</keyword>
  <keyword>rectal cancer, locally advanced</keyword>
  <keyword>Electrochemotherapy</keyword>
  <keyword>Electroporation</keyword>
  <keyword>Neoadjuvant therapy</keyword>
  <keyword>Antineoplastic, antibodies</keyword>
  <keyword>Bleomycin</keyword>
  <keyword>Pathologic processes</keyword>
  <keyword>Neoplastic processes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bleomycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</ipd_description>
  </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/NCT03040180
org study id: REG-32-2016
nct id: NCT03040180
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the efficacy and safety of neoadjuvant
      electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative
      clinical setting, using an endoscopic electroporation device (EndoVE).
Electroporation of cancer cells allows for a greater concentration of chemotherapy drugs to
      enter the tumor cells. The uptake of the chemotherapeutic drug is aided through the
      application of short electric pulses to the tumor mass (referred to as - Electrochemotherapy
      or ECT). The pulses make the tumor cells more porous which allows the drug easier access into
      the cancer cells, whereas other tissues and organs in the body remain relatively poor at
      absorbing the drug, thereby reducing the potential side effects on healthy tissues.
      Procedures with electrochemotherapy have previously been applied to human patients in other
      countries of the EU, the US and Japan.

      The drug concentration used is significantly reduced due to the more targeted absorption by
      the tumor and this significantly reduces side effects normally associated with chemotherapy.

      A large number of preclinical and clinical Phase I and I/II studies have demonstrated the
      efficiency and safety of ECT. These studies have included patients with melanoma, head and
      neck squamous cell carcinoma, merkel cell carcinomas, basal cell carcinoma and adenocarcinoma
      nodules.

      An endoscopic system (EndoVE ) for delivering the electric pulses to gastrointestinal tumors
      has recently been developed. The treatment procedure is similar to standard endoscopic
      colorectal examination (therapeutic colonoscopy) with the added element of an intravenous
      injection of bleomycin followed by the delivery of electric pulses (each one less than 1msec
      in duration). The pulses are endoscopically delivered directly to the tumor mass. The entire
      procedure is minimally invasive and completely ambulatory. A successful treatment will cause
      the tumor to shrink in size in the weeks following the procedure.

      The objective of this study is to investigate the efficacy and safety of this approach in
      downsizing locally advanced rectal tumors prior to intended curative surgery.

      Time frame:

        1. All patients will be treated with standard neoadjuvant chemoradiation therapy prior to
           enrollment in this trial.

        2. Alle patients will have PET/MRI scans performed twice to evaluate treatment response
           (before and after ECT)

        3. ECT treatment will be performed 4 weeks prior to surgery outlined by MDT.

        4. Alle patients will be followed up for 3 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Histopathologic tumor regression following electrochemotherapy
time frame: 4 weeks
description: Number of participants with histopathologic tumor regression following elctrochemotherapy as assesed by histopathological evaluation of Tumor Regression Grade (Mandard Classification, TRG 1-5)
measure: Treatment safety of electrochemotherapy
time frame: 4 months
description: Number of participants with treatment-related adverse events as assesed by CTCAE version 4.0
measure: Treatment safety of surgery following electrochemotherapy
time frame: 4 weeks
description: Number of participants with compromized surgery following electrochemotherapy assesed by R1 resection rate, CRM involvement, non-mesorectal resection plane, and post operative complications according to Clavien-Dindo Classification
measure: Tumor regression according to Hybrid PET/MRI following electrochemotherapy
time frame: 4 weeks
description: Tumor regression as assesed by tumor stage (T-stage)
measure: Tumor Immunologic response following electrochemotherapy
time frame: 4 weeks
description: Tumor immunologic infiltration as assesed by the Immunoscore through immunohistochemical analysis
arm group label: Electrochemotherapy with bleomycin
arm group type: Experimental
description: Systemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA.
BSA by Du Bois formula.
arm group label: Standard care
arm group type: No Intervention
description: Standard care
intervention type: Drug
intervention name: Electrochemotherapy with bleomycin
description: Systemic injection, once only treatment
arm group label: Electrochemotherapy with bleomycin
other name: ATC code L01DC01
other name: EV substance code SUB00844MIG
intervention type: Device
intervention name: EndoVE
description: Electroporation using an endoscopic electroporation device
arm group label: Electrochemotherapy with bleomycin
other name: Endoscopic electroporation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ismail Gögenur, Professor
role: Principal Investigator
affiliation: Department of Surgery, Zealand University Hospital
last name: Julie Gehl, MD, DMSc
role: Principal Investigator
affiliation: Department of oncology, herlev Hospital
last name: Ismail Gögenur, MD, DMSc
phone: +45 26336426
email: igo@regionsjaelland.dk
last name: Rasmus P Vogelsang, MD
phone: +45 27351103
email: rvo@regionsjaelland.dk
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Denmark
responsible party type: Sponsor
mesh term: Rectal Neoplasms
mesh term: Bleomycin
sharing ipd: Undecided
ipd description: Undecided