<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/NCT01720407</url>
  </required_header>
  <id_info>
    <org_study_id>BRD/11/06-S</org_study_id>
    <nct_id>NCT01720407</nct_id>
  </id_info>
  <brief_title>Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face</brief_title>
  <acronym>ImiReduc</acronym>
  <official_title>Relevance of Imiquimod as Neo-adjuvant Treatment to Reduce Excision Size and the Risk of Intralesional Excision in Lentigo Malignant of the Face</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MEDA Pharma GmbH &amp; Co. KG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Nantes University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lentigo malignant (LM) is an intraepidermal melanocytic proliferation occurring on&#xD;
      photoexposed skin. In our project, this term applies both to Dubreuilh's melanosis and to&#xD;
      Dubreuilh's intraepidermal melanoma. It consequently excludes invasive melanoma. Although&#xD;
      surgery is the treatment of choice, it remains without consensus on the margins (5 mm or 10&#xD;
      mm) excision for a localized tumor on the face.&#xD;
&#xD;
      Several studies have shown that imiquimod, activating local immunity by interferon&#xD;
      production, induced LM or MLM regression and could also decrease the frequency of relapses.&#xD;
&#xD;
      The principal aim of our project is to study the effect of imiquimod versus placebo in&#xD;
      pre-operative neoadjuvant treatment aimed at reducing both surgical margins, as from the&#xD;
      first surgical procedure, and the frequency of short and medium term recurrence of LM.&#xD;
      Furthermore, the improvement in patient quality of life could also be significant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary endpoint of the study is to demonstrate that neoadjuvant treatment of LM by&#xD;
      imiquimod prior to surgery can reduce the frequency of intralesional excisions as from the&#xD;
      first surgical procedure, with a healthy tissue margin of 5mm. Furthermore, the improvement&#xD;
      in patient quality of life could also be significant.&#xD;
&#xD;
      The number of patients to be included in the study is 268.&#xD;
&#xD;
      For each patient, the study will involve several stages (S), as follows:&#xD;
&#xD;
      S0 (Selection): information and obtaining of the patient's informed consent. Performance of&#xD;
      biopsy for histological confirmation of LM&#xD;
&#xD;
      S1 (S0 + ~ 2 weeks): patient inclusion following anatomopathological confirmation of LM.&#xD;
      Patient randomisation in one or other study arm: imiquimod versus placebo and initiation of&#xD;
      topical treatment.&#xD;
&#xD;
      S2 (S1 + 4 weeks): Discontinuation of imiquimod/placebo application. Scheduling of the&#xD;
      surgical procedure 4 weeks later.&#xD;
&#xD;
      S3 (S2 + 4 weeks): Surgery.&#xD;
&#xD;
      S4: After the last surgical procedure, simple clinical follow up will be ensured every 6&#xD;
      months for a period of 3 years, in order to study the recurrence rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2012</start_date>
  <completion_date type="Actual">November 10, 2022</completion_date>
  <primary_completion_date type="Actual">October 2019</primary_completion_date>
  <phase>Phase 3</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>
    <masking_description>Surgeon does not know the result of randomization.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The primary endpoint is the margin of resection. Success is defined by an extralesional excision as from the first surgical procedure performed with a healthy tissue margin of 5 mm.</measure>
    <time_frame>10 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of surgical re-excisions required to obtain complete remission.</measure>
    <time_frame>Baseline, 2 months till 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of recurrences, defined as the reappearance of pigmentation within 3 years of surgical excision.</measure>
    <time_frame>Baseline, 2 months till 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of histologically confirmed complete remissions under imiquimod.</measure>
    <time_frame>Baseline, 2 months till 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">259</enrollment>
  <condition>Lentigo Maligna Melanoma (Head or Neck)</condition>
  <arm_group>
    <arm_group_label>Imiquimod</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Imiquimod cream + surgery</intervention_name>
    <description>Imiquimod (5 times per week) applied to and extending 1cm beyond the lesion for a period of 4 weeks (i.e. a total of 20 applications), followed by surgery performed four weeks after the last application of the topical treatment. If excision is intralesional, re-excision at 5mm will be performed within a few days (equivalent to 2-stage surgery).</description>
    <arm_group_label>Imiquimod</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo + surgery</intervention_name>
    <description>Placebo (5 times per week) applied to and extending 1cm beyond the lesion for a period of 4 weeks, followed by surgery performed four weeks after the last application of the topical treatment. If excision is intralesional, re-excision of 5mm of clinically healthy tissue will be performed within a few days (equivalent to 2-stage surgery).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients from both sexes aged over 18 years and operable&#xD;
&#xD;
          -  Presenting with LM of the face, the neck, or the scalp (in case of hairless scalp&#xD;
             only) histologically confirmed by biopsy&#xD;
&#xD;
          -  Patients presenting with a primitive lesion, of a surface ≥ to 1cm² and ≤ to 20cm²,&#xD;
             with the possibility of graft or flap reconstruction&#xD;
&#xD;
          -  LM previously untreated by surgery&#xD;
&#xD;
          -  LM without prior treatment with liquid nitrogen or any other local treatment within 3&#xD;
             months&#xD;
&#xD;
          -  ECOG ≤ 2&#xD;
&#xD;
          -  Leucocytes ≥ 3,000/mm³&#xD;
&#xD;
          -  Neutrophil count ≥ 1,500/mm³&#xD;
&#xD;
          -  Platelet count ≥ 100,000/mm³&#xD;
&#xD;
          -  Haemoglobin ≥ 9.0g/dL&#xD;
&#xD;
          -  Absence of severe evolutive infection&#xD;
&#xD;
          -  Absence of known HIV infection&#xD;
&#xD;
          -  Absence of corticotherapy and treatment by immunosuppressive agents&#xD;
&#xD;
          -  Absence of excoriation and scarring biopsy prior to application of study treatment&#xD;
&#xD;
          -  Membership to a social security insurance scheme.&#xD;
&#xD;
          -  Negative pregnancy test conducted during the inclusion consultation for non-menopausal&#xD;
             women.&#xD;
&#xD;
          -  Effective contraception for patients of childbearing age&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  LM located on the eyelids are excluded, together with LM in anatomic sites other than&#xD;
             the face, the neck or the scalp&#xD;
&#xD;
          -  Melanomas other than LM&#xD;
&#xD;
          -  Invasive LM&#xD;
&#xD;
          -  LM with a surface area &lt; to 1cm² or &gt; to 20cm²&#xD;
&#xD;
          -  LM of which the macroscopic contours cannot be defined&#xD;
&#xD;
          -  Patients who are allergic to imiquimod excipient (eg hydroxybenzoate)&#xD;
&#xD;
          -  Patients with a hypersensitivity to active substances or to any of the excipients of&#xD;
             the placebo (for example propyl parahydroxybenzoate)&#xD;
&#xD;
          -  Patients treated by immunosuppressive agents, immunomodulators, cytotoxic agents or&#xD;
             corticosteroids (local and systemic) during the 4-week period prior to the selection&#xD;
             visit&#xD;
&#xD;
          -  Patients with auto-immune disease (except vitiligo) or transplant patients&#xD;
&#xD;
          -  Cutaneous reconstruction not possible&#xD;
&#xD;
          -  Presence of associated evolutive neoplasia since less than 5 years (with the exception&#xD;
             of basal cell carcinoma, Bowen's carcinoma and carcinoma in situ of the cervix)&#xD;
&#xD;
          -  Patient refusing surgery under local or general anaesthesia&#xD;
&#xD;
          -  Pregnant women&#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>Brigitte Dréno, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nantes University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Hôpital Haut-Lévêque</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Hôpital Saint André</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP Hôpital Ambroise Paré</name>
      <address>
        <city>Boulogne Billancourt</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Michallon</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH</name>
      <address>
        <city>Le Mans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HM</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Orléans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP Hôpital Saint Louis</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Milétrie</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Saint-Etienne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu (Iucto)</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>October 23, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <last_update_submitted>December 5, 2022</last_update_submitted>
  <last_update_submitted_qc>December 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dermatology/ Skin cancers/Lentigo maligna melanoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Hutchinson's Melanotic Freckle</mesh_term>
    <mesh_term>Lentigo</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Imiquimod</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/NCT01720407
org study id: BRD/11/06-S
nct id: NCT01720407
lead sponsor: 
collaborator: 
has dmc: No
Lentigo malignant (LM) is an intraepidermal melanocytic proliferation occurring on
      photoexposed skin. In our project, this term applies both to Dubreuilh's melanosis and to
      Dubreuilh's intraepidermal melanoma. It consequently excludes invasive melanoma. Although
      surgery is the treatment of choice, it remains without consensus on the margins (5 mm or 10
      mm) excision for a localized tumor on the face.

      Several studies have shown that imiquimod, activating local immunity by interferon
      production, induced LM or MLM regression and could also decrease the frequency of relapses.

      The principal aim of our project is to study the effect of imiquimod versus placebo in
      pre-operative neoadjuvant treatment aimed at reducing both surgical margins, as from the
      first surgical procedure, and the frequency of short and medium term recurrence of LM.
      Furthermore, the improvement in patient quality of life could also be significant.
The primary endpoint of the study is to demonstrate that neoadjuvant treatment of LM by
      imiquimod prior to surgery can reduce the frequency of intralesional excisions as from the
      first surgical procedure, with a healthy tissue margin of 5mm. Furthermore, the improvement
      in patient quality of life could also be significant.

      The number of patients to be included in the study is 268.

      For each patient, the study will involve several stages (S), as follows:

      S0 (Selection): information and obtaining of the patient's informed consent. Performance of
      biopsy for histological confirmation of LM

      S1 (S0 + ~ 2 weeks): patient inclusion following anatomopathological confirmation of LM.
      Patient randomisation in one or other study arm: imiquimod versus placebo and initiation of
      topical treatment.

      S2 (S1 + 4 weeks): Discontinuation of imiquimod/placebo application. Scheduling of the
      surgical procedure 4 weeks later.

      S3 (S2 + 4 weeks): Surgery.

      S4: After the last surgical procedure, simple clinical follow up will be ensured every 6
      months for a period of 3 years, in order to study the recurrence rate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Surgeon does not know the result of randomization.
measure: The primary endpoint is the margin of resection. Success is defined by an extralesional excision as from the first surgical procedure performed with a healthy tissue margin of 5 mm.
time frame: 10 weeks
measure: The number of surgical re-excisions required to obtain complete remission.
time frame: Baseline, 2 months till 3 years
measure: The number of recurrences, defined as the reappearance of pigmentation within 3 years of surgical excision.
time frame: Baseline, 2 months till 3 years
measure: The number of histologically confirmed complete remissions under imiquimod.
time frame: Baseline, 2 months till 3 years
arm group label: Imiquimod
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Imiquimod cream + surgery
description: Imiquimod (5 times per week) applied to and extending 1cm beyond the lesion for a period of 4 weeks (i.e. a total of 20 applications), followed by surgery performed four weeks after the last application of the topical treatment. If excision is intralesional, re-excision at 5mm will be performed within a few days (equivalent to 2-stage surgery).
arm group label: Imiquimod
intervention type: Drug
intervention name: Placebo + surgery
description: Placebo (5 times per week) applied to and extending 1cm beyond the lesion for a period of 4 weeks, followed by surgery performed four weeks after the last application of the topical treatment. If excision is intralesional, re-excision of 5mm of clinically healthy tissue will be performed within a few days (equivalent to 2-stage surgery).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Brigitte Dréno, MD, PhD
role: Principal Investigator
affiliation: Nantes University Hospital
facility: 
facility: 
facility: 
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country: France
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Hutchinson's Melanotic Freckle
mesh term: Lentigo
mesh term: Imiquimod