<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/NCT03784625</url>
  </required_header>
  <id_info>
    <org_study_id>2016-002444-17</org_study_id>
    <secondary_id>TRANSLA12-143</secondary_id>
    <nct_id>NCT03784625</nct_id>
  </id_info>
  <brief_title>Targeted Radionuclide Therapy for Metastatic Melanoma [131I] ICF01012</brief_title>
  <acronym>MELRIV-1</acronym>
  <official_title>Targeted Radionuclide Therapy for Metastatic Melanoma [131I] ICF01012: Phase I Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Jean Perrin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Jean Perrin</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a phase I clinical trial aimed to determine the recommended dose of&#xD;
      [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma&#xD;
      (binding [131I]ICF01012 ). The [131I]ICF01012 is a targeted radionuclide therapy with a high&#xD;
      affinity for melanin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will include a maximum of 36 patients. This study will begin with a preselection&#xD;
      part that consists of an injection of [131I]ICF01012 at a diagnostic dose (185 MBq) in order&#xD;
      to preselect patients who will receive the therapeutic dose according to the dosimetry&#xD;
      results : binding of [131I]ICF01012 on at least a tumoral lesion and an acceptable radiation&#xD;
      absorbed dose to major organs.&#xD;
&#xD;
      The second phase will consist of a therapeutic part with a single administration of&#xD;
      [131I]ICF01012 at a therapeutic dose. This part is a dose escalation model (4 levels of&#xD;
      therapeutic dose were tested)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 18, 2019</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>dose escalation model</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of the recommended therapeutic dose of [131I] ICF01012</measure>
    <time_frame>Only toxicities observed during the 6 weeks following administration of the therapeutic dose will be considered for the evaluation of DLT</time_frame>
    <description>defined as the highest dose at which the percentage of DLT (dose limiting toxicity) is less than 33%. The DLT is defined as:&#xD;
all non hematologic toxicities NCI-CTC grade 3-4 except for alopecia, nausea, vomiting and fever that can be controlled by appropriate measures.&#xD;
hematologic toxicities as thrombopenia and anemia of grade 4, neutropenia of grade 4 for more than 5 days, thrombopenia of grade 3 with bleeding and all other hematologic toxicities of grade 3 clinically significant of more than 3 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the sensitivity and specificity by patients and by lesions of [131I]ICF01012 ICF01012 for the visualization of metastatic melanoma lesions from the examinations made during the selection phase</measure>
    <time_frame>selection phase Day 0 - Day 7</time_frame>
    <description>binding of [131I]ICF01012 compared to standard evaluation of metastatic lesion (standard imaging (CT Scan, TEP ...) or clinical evaluation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the tolerance of [131I] ICF01012 (adverse events assessed by NCI-CTC Version 4.03)</measure>
    <time_frame>from the the first dose to the end of study (3 months after diagnostic dose)</time_frame>
    <description>adverse events assessed by NCI-CTC Version 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of [131I] ICF01012 including the study of biodistribution and excretion (radiation counting of serum, whole blood and urinary samples)</measure>
    <time_frame>selection phase Day 0 (diagnostic dose), Day 1, and Day 4, Day 7</time_frame>
    <description>radiation counting of serum, whole blood and urinary samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the therapeutic response of [131I] ICF01012.</measure>
    <time_frame>at 3 months</time_frame>
    <description>Response will be categorized according to the criteria from RECIST 1.1 and PERCIST criteria: complete response, partial response, stable disease and progressive disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of personal dosimetry for the administration of [131I]ICF01012.</measure>
    <time_frame>Selection phase : Day 0, Day 1, Day 4, and Day 7; therapeutic phase : Day 15, Day 18 and Day 25, Day 74</time_frame>
    <description>assessed by whole-body planar studies and tomographic imaging with single-photon emission computed tomography (SPECT)/CT</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>therapeutic dose activity (level 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>[131]ICF01012 at a therapeutic dose of 800 MBq/m² , single dose at D11 (intravenous administration)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>therapeutic dose activity (level 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>[131]ICF01012 at a therapeutic dose of 1600 MBq/m² , single dose at D11 (intravenous administration)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>therapeutic dose activity (level 3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>[131]ICF01012 at a therapeutic dose of 2700 MBq/m² , single dose at D11 (intravenous administration)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>therapeutic dose activity (level 4)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>[131]ICF01012 at a therapeutic dose of 4000 MBq/m² , single dose at D11 (intravenous administration)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[131I]ICF01012 (therapeutic dose level 1)</intervention_name>
    <description>1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, an acceptable radiation absorbed dose to major organs)&#xD;
1 therapeutic injection (D11) at a dose of 800 MBq/m²</description>
    <arm_group_label>therapeutic dose activity (level 1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[131I]ICF01012 (therapeutic dose level 2)</intervention_name>
    <description>1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, an acceptable radiation absorbed dose to major organs)&#xD;
1 therapeutic injection (D11) at a dose of 1600 MBq/m²</description>
    <arm_group_label>therapeutic dose activity (level 2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[131I]ICF01012 (therapeutic dose level 3)</intervention_name>
    <description>1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, and an acceptable radiation absorbed dose to major organs)&#xD;
1 therapeutic injection (D11) at a dose of 2700 MBq/m²</description>
    <arm_group_label>therapeutic dose activity (level 3)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[131I]ICF01012 (therapeutic dose level 4)</intervention_name>
    <description>1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, and an acceptable radiation absorbed dose to major organs)&#xD;
1 therapeutic injection (D11) at a dose of 4000 MBq/m²</description>
    <arm_group_label>therapeutic dose activity (level 4)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient with metastatic melanoma failure to recommended treatments by HAS.&#xD;
&#xD;
          -  Initial histological diagnosis of cutaneous melanoma pigmented or unknown status or&#xD;
             choroidal melanoma.&#xD;
&#xD;
          -  Presence of at least one measurable lesion and / or evaluable in 18FDG-PET as PERCIST&#xD;
             criteria.&#xD;
&#xD;
          -  Presence of at least one measurable lesion and / or evaluable as CT RECIST 1.1&#xD;
             criteria.&#xD;
&#xD;
          -  WHO performance index ≤ 2 .&#xD;
&#xD;
          -  Age&gt; 18 years&#xD;
&#xD;
          -  Life expectancy&gt; 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Brain metastases symptomatic&#xD;
&#xD;
          -  Patient with a VI skin phototype&#xD;
&#xD;
          -  Previous treatment with chemotherapy, radiotherapy, immunotherapy and targeted therapy&#xD;
             in the previous 4 weeks, the first injection of [131I] ICF01012&#xD;
&#xD;
          -  Pregnant woman, nursing or woman of childbearing age refusing to follow effective&#xD;
             contraception during treatment and 12 months after the administration of therapeutic&#xD;
             dose.&#xD;
&#xD;
          -  Men refusing to follow effective contraception during treatment and 12 months after&#xD;
             the administration of therapeutic dose&#xD;
&#xD;
          -  Other evolutionary known cancer in the past five years&#xD;
&#xD;
          -  Earlier irradiation of more than 25% of the bone marrow&#xD;
&#xD;
          -  Suspicion of invasion of more than 25% of the bone marrow on imaging 18F-FDG PET-CT&#xD;
&#xD;
          -  External Radiotherapy on target organs or the maximum dose as recommended in force&#xD;
&#xD;
          -  Uncontrolled diabetes&#xD;
&#xD;
          -  Known history of allergy to the excipients of the solution of [131I]ICF01012&#xD;
&#xD;
          -  Any comorbidity or severe disease at the discretion of the investigator&#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>Florent CACHIN, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Jean Perrin</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Florent CACHIN, Pr</last_name>
    <phone>33473278089</phone>
    <email>florent.CACHIN@clermont.unicancer.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Centre Jean Perrin</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Florent Cachin, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Florent Cachin, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandrine Mansard, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sandrine Mansard, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>February 3, 2023</last_update_submitted>
  <last_update_submitted_qc>February 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>metastatic melanoma</keyword>
  <keyword>targeted radionuclide therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_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/NCT03784625
org study id: 2016-002444-17
secondary id: TRANSLA12-143
nct id: NCT03784625
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is a phase I clinical trial aimed to determine the recommended dose of
      [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma
      (binding [131I]ICF01012 ). The [131I]ICF01012 is a targeted radionuclide therapy with a high
      affinity for melanin.
This study will include a maximum of 36 patients. This study will begin with a preselection
      part that consists of an injection of [131I]ICF01012 at a diagnostic dose (185 MBq) in order
      to preselect patients who will receive the therapeutic dose according to the dosimetry
      results : binding of [131I]ICF01012 on at least a tumoral lesion and an acceptable radiation
      absorbed dose to major organs.

      The second phase will consist of a therapeutic part with a single administration of
      [131I]ICF01012 at a therapeutic dose. This part is a dose escalation model (4 levels of
      therapeutic dose were tested)
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: dose escalation model
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluation of the recommended therapeutic dose of [131I] ICF01012
time frame: Only toxicities observed during the 6 weeks following administration of the therapeutic dose will be considered for the evaluation of DLT
description: defined as the highest dose at which the percentage of DLT (dose limiting toxicity) is less than 33%. The DLT is defined as:
all non hematologic toxicities NCI-CTC grade 3-4 except for alopecia, nausea, vomiting and fever that can be controlled by appropriate measures.
hematologic toxicities as thrombopenia and anemia of grade 4, neutropenia of grade 4 for more than 5 days, thrombopenia of grade 3 with bleeding and all other hematologic toxicities of grade 3 clinically significant of more than 3 weeks
measure: Evaluation of the sensitivity and specificity by patients and by lesions of [131I]ICF01012 ICF01012 for the visualization of metastatic melanoma lesions from the examinations made during the selection phase
time frame: selection phase Day 0 - Day 7
description: binding of [131I]ICF01012 compared to standard evaluation of metastatic lesion (standard imaging (CT Scan, TEP ...) or clinical evaluation)
measure: Evaluation of the tolerance of [131I] ICF01012 (adverse events assessed by NCI-CTC Version 4.03)
time frame: from the the first dose to the end of study (3 months after diagnostic dose)
description: adverse events assessed by NCI-CTC Version 4.03
measure: Pharmacokinetics of [131I] ICF01012 including the study of biodistribution and excretion (radiation counting of serum, whole blood and urinary samples)
time frame: selection phase Day 0 (diagnostic dose), Day 1, and Day 4, Day 7
description: radiation counting of serum, whole blood and urinary samples
measure: Evaluation of the therapeutic response of [131I] ICF01012.
time frame: at 3 months
description: Response will be categorized according to the criteria from RECIST 1.1 and PERCIST criteria: complete response, partial response, stable disease and progressive disease
measure: Evaluation of personal dosimetry for the administration of [131I]ICF01012.
time frame: Selection phase : Day 0, Day 1, Day 4, and Day 7; therapeutic phase : Day 15, Day 18 and Day 25, Day 74
description: assessed by whole-body planar studies and tomographic imaging with single-photon emission computed tomography (SPECT)/CT
arm group label: therapeutic dose activity (level 1)
arm group type: Experimental
description: [131]ICF01012 at a therapeutic dose of 800 MBq/m² , single dose at D11 (intravenous administration)
arm group label: therapeutic dose activity (level 2)
arm group type: Experimental
description: [131]ICF01012 at a therapeutic dose of 1600 MBq/m² , single dose at D11 (intravenous administration)
arm group label: therapeutic dose activity (level 3)
arm group type: Experimental
description: [131]ICF01012 at a therapeutic dose of 2700 MBq/m² , single dose at D11 (intravenous administration)
arm group label: therapeutic dose activity (level 4)
arm group type: Experimental
description: [131]ICF01012 at a therapeutic dose of 4000 MBq/m² , single dose at D11 (intravenous administration)
intervention type: Drug
intervention name: [131I]ICF01012 (therapeutic dose level 1)
description: 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, an acceptable radiation absorbed dose to major organs)
1 therapeutic injection (D11) at a dose of 800 MBq/m²
arm group label: therapeutic dose activity (level 1)
intervention type: Drug
intervention name: [131I]ICF01012 (therapeutic dose level 2)
description: 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, an acceptable radiation absorbed dose to major organs)
1 therapeutic injection (D11) at a dose of 1600 MBq/m²
arm group label: therapeutic dose activity (level 2)
intervention type: Drug
intervention name: [131I]ICF01012 (therapeutic dose level 3)
description: 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, and an acceptable radiation absorbed dose to major organs)
1 therapeutic injection (D11) at a dose of 2700 MBq/m²
arm group label: therapeutic dose activity (level 3)
intervention type: Drug
intervention name: [131I]ICF01012 (therapeutic dose level 4)
description: 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, and an acceptable radiation absorbed dose to major organs)
1 therapeutic injection (D11) at a dose of 4000 MBq/m²
arm group label: therapeutic dose activity (level 4)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Florent CACHIN, Pr
role: Principal Investigator
affiliation: Centre Jean Perrin
last name: Florent CACHIN, Pr
phone: 33473278089
email: florent.CACHIN@clermont.unicancer.fr
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: No