<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/NCT01676779</url>
  </required_header>
  <id_info>
    <org_study_id>DC-MEL</org_study_id>
    <nct_id>NCT01676779</nct_id>
  </id_info>
  <brief_title>mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma</brief_title>
  <acronym>DC-MEL</acronym>
  <official_title>Randomized Controlled Phase II Clinical Trial on mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma Patients Who Are Disease-free Following the Local Treatment of Macrometastases.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitair Ziekenhuis Brussel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>RIZIV</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitair Ziekenhuis Brussel</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with&#xD;
      AJCC stage IIIB/C &amp; -IV melanoma. At baseline tumor assessment (using total body FDG-PET/CT),&#xD;
      patients should be free from measurable tumor lesions (according to RECISTv1.1 definitions)&#xD;
      following prior local therapy (e.g. following surgical resection, isolated limb perfusion,&#xD;
      radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, …). Patients should&#xD;
      not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural&#xD;
      effusion), and lesions treated by prior local therapy should be free from progression.&#xD;
      Patients should not have received any prior systemic therapy (non-experimental or&#xD;
      experimental).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with&#xD;
      AJCC stage IIIB/C &amp; -IV melanoma. At baseline tumor assessment (using total body FDG-PET/CT),&#xD;
      patients should be free from measurable tumor lesions (according to RECISTv1.1 definitions)&#xD;
      following prior local therapy (e.g. following surgical resection, isolated limb perfusion,&#xD;
      radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, …). Patients should&#xD;
      not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural&#xD;
      effusion), and lesions treated by prior local therapy should be free from progression.&#xD;
      Patients should not have received any prior systemic therapy (non-experimental or&#xD;
      experimental).&#xD;
&#xD;
        -  Patients will be randomized between two treatment arms (Arm-A and -B). In study Arm-A,&#xD;
           patients will receive DC-administrations during one year following randomization.&#xD;
           Salvage treatment by local therapies will be allowed during the study treatment in&#xD;
           Arm-A. In study Arm-B, patients will initiate DC-administrations only after documented&#xD;
           recurrence of the melanoma that cannot be salvaged by local therapy.&#xD;
&#xD;
        -  The primary endpoint of this clinical trial is to determine the rate (%) of patients who&#xD;
           are free from macrometastases (: measurable tumor lesions and symptomatic non-measurable&#xD;
           tumor lesions) at 1-year (= 52 weeks) after randomization.&#xD;
&#xD;
      Patients treated on Arm-B will serve as a contemporary control-arm to help interpreting the&#xD;
      outcome of patients treated in Arm-A. By design (phase II) this trial will not be powered to&#xD;
      statistically prove a predefined difference between the two study arms (this would require a&#xD;
      phase III design). Patients treated in Arm-B will be able to initiate immunotherapy with&#xD;
      autologous DC at the time of recurrence that can not be salvaged by local therapy.&#xD;
      Documentation of the anti-tumor activity and survival following DC-treatment at recurrence in&#xD;
      Arm-B patients will be a secondary objective of this clinical trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2015</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>1-year disease free survival percentage</measure>
    <time_frame>1-year following recruitment date</time_frame>
    <description>Patients will be evaluated 52 weeks following randomization for their melanoma disease status (= macro-metastases present or absent)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>safety</measure>
    <time_frame>continuous during the study (52weeks after start)</time_frame>
    <description>Patients will be followed continuous during their study participation for adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">88</enrollment>
  <condition>Malignant Melanoma Stage III</condition>
  <condition>Malignant Melanoma Stage IV</condition>
  <arm_group>
    <arm_group_label>Arm A dendritic cell therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm-A, patients will receive Dendritic Cell therapy during one year following randomization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B Dendritic cell therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm-B, patients will initiate Dendritic Cell therapy only after documented recurrence of the melanoma that cannot be salvaged by local therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Dendritic cell therapy</intervention_name>
    <description>Dendritic cell therapy IV and ID</description>
    <arm_group_label>Arm A dendritic cell therapy</arm_group_label>
    <arm_group_label>Arm B Dendritic cell therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able and willing to give written informed consent&#xD;
&#xD;
          2. Histological documentation of AJCC stage III or stage IV melanoma&#xD;
&#xD;
          3. melanoma (melanoma originating in the choroid, iris or ciliar body are not eligible)&#xD;
&#xD;
          4. baseline tumor assessment by whole-body FDG-PET/CT, patients should be free from&#xD;
             measurable tumor lesions (RECIST (v1.1)), and free from symptomatic non-measurable&#xD;
             tumor lesions&#xD;
&#xD;
          5. Prior local treatment of primary and metastatic tumor lesions is allowed . Treated&#xD;
             tumor lesions should be free from progression at baseline assessment&#xD;
&#xD;
          6. Normal organ function and normal hematological parameters;laboratory parameters should&#xD;
             be within normal range, except following laboratory parameters:HEMOGLOBIN ≥ 10 G/DL;&#xD;
             GRANULOCYTES ≥ 1,500/µL; LYMPHOCYTES ≥ 1000/µL; PLATELETS ≥ 100,000/µL; SERUM&#xD;
             CREATININ ≤ 2.0 MG/DL; SERUM BILIRUBIN ≤ 2.0 MG/DL; AST AND ALT ≤ 2 X THE NORMAL UPPER&#xD;
             LIMITS; LDH ≤ 1,5X NORMAL UPPER LIMIT; CRP ≤ 1,5X NORMAL UPPER LIMIT; PROTHROMBIN TIME&#xD;
             (PT) INTERNATIONAL NORMALIZED RATIO (INR) AND PARTIAL THROMBOPLASTIN TIME (PTT) WITHIN&#xD;
             NORMAL LIMITS&#xD;
&#xD;
          7. Negative serology for HCV, and HIV; absence of active infection with HBV, and&#xD;
             Syphilis; If positive results for HepB or Syphilis indicate immunity and are not&#xD;
             indicative of active infection, the patient can enter the study.&#xD;
&#xD;
          8. Adequate venous access(to undergo leukapheresis)&#xD;
&#xD;
          9. No prior systemic therapy for melanoma&#xD;
&#xD;
         10. Full recovery from all prior therapies. A period of 4 weeks following major surgery,&#xD;
             radiation therapy, or ILP, or any other major invasive procedure is required&#xD;
&#xD;
         11. Baseline WHO performance status of 0 or 1&#xD;
&#xD;
         12. Male and female patients ≥ 18 years&#xD;
&#xD;
         13. No need for uninterrupted therapeutic anticoagulation&#xD;
&#xD;
         14. No prior history of a serious autoimmune disorder&#xD;
&#xD;
         15. No concomitant medication with immune suppressive drugs&#xD;
&#xD;
         16. Women of childbearing potential must be using an adequate method of contraception to&#xD;
             avoid pregnancy throughout the study and for up to 8 weeks after the study in such a&#xD;
             manner that the risk of pregnancy is minimized.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of immunodeficiency or autoimmune disease requiring medical treatment (e.g.&#xD;
             corticosteroids or other immunosuppressive drugs).Vitiligo is not an exclusion&#xD;
             criterion&#xD;
&#xD;
          2. Any serious acute or chronic illnesses (e.g. heart disease NYHA Class III or&#xD;
             IV,renal-,liver- or pulmonary insufficiency) or other conditions requiring concurrent&#xD;
             medications not allowed during this study (e.g. active chronic infections requiring&#xD;
             antibiotics)&#xD;
&#xD;
          3. History of malignancy. Curatively treated cervical carcinoma in situ,or squamous-,or&#xD;
             basal cell carcinoma of the skin, or subjects who have been treated and&#xD;
             recurrence-free of other malignancies for more than 5 years following the diagnosis&#xD;
             are eligible&#xD;
&#xD;
          4. Inability to undergo FDG-PET/CT, or MRI examination&#xD;
&#xD;
          5. Mental impairment that may compromise the ability to give informed consent and comply&#xD;
             with the requirements of the study&#xD;
&#xD;
          6. Participation in any other clinical trial involving another investigational agent&#xD;
             within 4 weeks prior to enrollment&#xD;
&#xD;
          7. Subject is pregnant (positive serum beta-HCG test at screening) or is currently&#xD;
             breast-feeding, anticipates becoming pregnant/impregnating their partner during the&#xD;
             study or within 6 months after study participation, or subject does not agree to&#xD;
             follow acceptable methods of birth control, to avoid conception during the study and&#xD;
             for at least 6 months after receiving the last dose of study treatment&#xD;
&#xD;
          8. Current alcohol dependence or drug abuse&#xD;
&#xD;
          9. Known hypersensitivity to the study treatment&#xD;
&#xD;
         10. Legal incapacity or limited legal capacity&#xD;
&#xD;
         11. Presence of any psychological, familial, sociological, or geographical condition&#xD;
             potentially hampering compliance with the study protocol and follow-up schedule.&#xD;
&#xD;
         12. Signs and symptoms suggestive of transmissible spongiform encephalopathy,or family&#xD;
             members who suffer(ed) from such.&#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>Bart Neyns, Phd Md</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitair Ziekenhuis Brussel</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UZ Brussel</name>
      <address>
        <city>Brussel</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>May 23, 2017</last_update_submitted>
  <last_update_submitted_qc>May 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universitair Ziekenhuis Brussel</investigator_affiliation>
    <investigator_full_name>Bart Neyns</investigator_full_name>
    <investigator_title>Head of devision (Medical Oncology)</investigator_title>
  </responsible_party>
  <keyword>melanoma</keyword>
  <keyword>no evidence of disease</keyword>
  <keyword>resection</keyword>
  <keyword>macro-metastases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</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/NCT01676779
org study id: DC-MEL
nct id: NCT01676779
lead sponsor: 
collaborator: 
has dmc: No
This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with
      AJCC stage IIIB/C & -IV melanoma. At baseline tumor assessment (using total body FDG-PET/CT),
      patients should be free from measurable tumor lesions (according to RECISTv1.1 definitions)
      following prior local therapy (e.g. following surgical resection, isolated limb perfusion,
      radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, …). Patients should
      not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural
      effusion), and lesions treated by prior local therapy should be free from progression.
      Patients should not have received any prior systemic therapy (non-experimental or
      experimental).
This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with
      AJCC stage IIIB/C & -IV melanoma. At baseline tumor assessment (using total body FDG-PET/CT),
      patients should be free from measurable tumor lesions (according to RECISTv1.1 definitions)
      following prior local therapy (e.g. following surgical resection, isolated limb perfusion,
      radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, …). Patients should
      not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural
      effusion), and lesions treated by prior local therapy should be free from progression.
      Patients should not have received any prior systemic therapy (non-experimental or
      experimental).

        -  Patients will be randomized between two treatment arms (Arm-A and -B). In study Arm-A,
           patients will receive DC-administrations during one year following randomization.
           Salvage treatment by local therapies will be allowed during the study treatment in
           Arm-A. In study Arm-B, patients will initiate DC-administrations only after documented
           recurrence of the melanoma that cannot be salvaged by local therapy.

        -  The primary endpoint of this clinical trial is to determine the rate (%) of patients who
           are free from macrometastases (: measurable tumor lesions and symptomatic non-measurable
           tumor lesions) at 1-year (= 52 weeks) after randomization.

      Patients treated on Arm-B will serve as a contemporary control-arm to help interpreting the
      outcome of patients treated in Arm-A. By design (phase II) this trial will not be powered to
      statistically prove a predefined difference between the two study arms (this would require a
      phase III design). Patients treated in Arm-B will be able to initiate immunotherapy with
      autologous DC at the time of recurrence that can not be salvaged by local therapy.
      Documentation of the anti-tumor activity and survival following DC-treatment at recurrence in
      Arm-B patients will be a secondary objective of this clinical trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 1-year disease free survival percentage
time frame: 1-year following recruitment date
description: Patients will be evaluated 52 weeks following randomization for their melanoma disease status (= macro-metastases present or absent)
measure: safety
time frame: continuous during the study (52weeks after start)
description: Patients will be followed continuous during their study participation for adverse events
arm group label: Arm A dendritic cell therapy
arm group type: Experimental
description: Arm-A, patients will receive Dendritic Cell therapy during one year following randomization.
arm group label: Arm B Dendritic cell therapy
arm group type: Experimental
description: Arm-B, patients will initiate Dendritic Cell therapy only after documented recurrence of the melanoma that cannot be salvaged by local therapy.
intervention type: Biological
intervention name: Dendritic cell therapy
description: Dendritic cell therapy IV and ID
arm group label: Arm A dendritic cell therapy
arm group label: Arm B Dendritic cell therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bart Neyns, Phd Md
role: Principal Investigator
affiliation: Universitair Ziekenhuis Brussel
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: Universitair Ziekenhuis Brussel
investigator full name: Bart Neyns
investigator title: Head of devision (Medical Oncology)
mesh term: Melanoma