<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/NCT03244956</url>
  </required_header>
  <id_info>
    <org_study_id>2017-000742-21</org_study_id>
    <secondary_id>2017/2527</secondary_id>
    <nct_id>NCT03244956</nct_id>
  </id_info>
  <brief_title>Efficacy of MEK (Trametinib) and BRAFV600E (Dabrafenib) Inhibitors With Radioactive Iodine (RAI) for the Treatment of Refractory Metastatic Differentiated Thyroid Cancer</brief_title>
  <acronym>MERAIODE</acronym>
  <official_title>Efficacy of a Selective MEK (Trametinib) and BRAFV600E (Dabrafenib) Inhibitors Associated With Radioactive Iodine (RAI) for the Treatment of Refractory Metastatic Differentiated Thyroid Cancer With RAS or BRAFV600E Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gustave Roussy, Cancer Campus, Grand Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gustave Roussy, Cancer Campus, Grand Paris</source>
  <oversight_info>
    <has_dmc>No</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 is a multicentric prospective non-randomized phase II trial, with two independent arms:&#xD;
      one for patients with RAS mutation and one for patients with BRAFV600E mutation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 27, 2017</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">November 18, 2021</primary_completion_date>
  <phase>Phase 2</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>This is a multicentric prospective non-randomized phase II trial, with two independent arms: one for patients with RAS mutation and one for patients with BRAFV600E mutation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Evaluated 6 months after the first dose of trametinib or trametinib and dabrafenib followed by RAI treatment in each arms</time_frame>
    <description>Propotion of patients with a best overall response of Complete Response (CR) or a Partial Response (PR)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Metastatic Radioactive Iodine Refractory Thyroid Cancer Patients With RAS or BRAF Mutation</condition>
  <arm_group>
    <arm_group_label>patients with RAS mutation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>patients with BRAFV600E mutation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib</intervention_name>
    <description>2mg daily for a maximum of 6 weeks of treatment</description>
    <arm_group_label>patients with BRAFV600E mutation</arm_group_label>
    <arm_group_label>patients with RAS mutation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabrafenib</intervention_name>
    <description>150mg twice daily</description>
    <arm_group_label>patients with BRAFV600E mutation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>131I</intervention_name>
    <description>5.5 GBq</description>
    <arm_group_label>patients with BRAFV600E mutation</arm_group_label>
    <arm_group_label>patients with RAS mutation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhTSH</intervention_name>
    <description>0.9mg on two consecutive days after 35 days of treatment</description>
    <arm_group_label>patients with BRAFV600E mutation</arm_group_label>
    <arm_group_label>patients with RAS mutation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with thyroid carcinoma of follicular origin (papillary, follicular or poorly&#xD;
             differentiated and their respective variants)&#xD;
&#xD;
          -  Known positive RAS (NRAS or KRAS or HRAS) or BRAFV600E or K601E mutation (determined&#xD;
             on a previous analysis and/or on a representative formalin-fixed paraffin embedded&#xD;
             (FFPE) tumor samples sent for central testing or on a biopsy sample sent for central&#xD;
             testing).&#xD;
&#xD;
          -  Radioiodine-refractory disease defined by at least one of the following item:&#xD;
&#xD;
               1. Distant metastasis without radioiodine uptake on a posttherapeutic radioactive&#xD;
                  scan&#xD;
&#xD;
               2. Distant metastasis disclosing RECIST progression within 12 months after a RAI&#xD;
                  treatment&#xD;
&#xD;
          -  Measurable disease with at least one lesion &gt;/= 1.0 cm in the longest diameter for a&#xD;
             non-lymph node or &gt;/= 1.5 cm in the short axis for a lymph node, measured with spiral&#xD;
             computed tomography (CT) without iv contrast injection or magnetic resonance imaging&#xD;
             (MRI) according to RECIST 1.1&#xD;
&#xD;
          -  Progressive disease according to RECIST 1.1 criteria within 18 months prior initiation&#xD;
             of treatment&#xD;
&#xD;
          -  Absence of metastatic lesion &gt; 30mm&#xD;
&#xD;
          -  Previous cumulated activity of radioactive iodine ≤ 600 mCi (22.2GBq)&#xD;
&#xD;
          -  Patients may have received prior treatment with either 1 line of Tyrosine Kinase&#xD;
             Inhibitor or 1 line of immunotherapy (excluding anti BRAF or anti MEK treatment such&#xD;
             as sorafenib, dabrafenib, trametinib and selumitinib) but should be off treatment&#xD;
             within 28 days prior to treatment start&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1&#xD;
&#xD;
          -  Blood pressure (BP) ≤ 140/90 mm Hg at screening with or without antihypertensive&#xD;
             medications and no change in antihypertensive medications within 1 week prior to Cycle&#xD;
             1/Day 1&#xD;
&#xD;
          -  Creatinine clearance ≥50 mL/min according to the Cockcroft and Gault formula&#xD;
&#xD;
          -  Adequate bone marrow function with :&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥1.5 x 109/L&#xD;
&#xD;
               2. Hemoglobin ≥9.0 g/dL&#xD;
&#xD;
               3. Platelet count ≥100 x 109/L&#xD;
&#xD;
               4. Normal blood coagulation function as evidenced by an International Normalized&#xD;
                  Ratio (INR) ≤ 1.5&#xD;
&#xD;
          -  Adequate liver function with:&#xD;
&#xD;
               1. Bilirubin ≤1.5 × upper limit of normal (ULN) except for unconjugated&#xD;
                  hyperbilirubinemia or Gilbert's syndrome,&#xD;
&#xD;
               2. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate&#xD;
                  aminotransferase (AST) ≤3 × ULN (≤5 × ULN if subject has liver metastases).&#xD;
&#xD;
          -  Males or females age ≥ 18 years at the time of informed consent&#xD;
&#xD;
          -  Women of childbearing potential must have a negative urine or serum β-HCG pregnancy&#xD;
             test within 7 days prior to the administration of the first study treatment. Sexually&#xD;
             active women of childbearing potential must agree to use a highly effective method of&#xD;
             contraception during the study and for at least 12 months after the last study&#xD;
             treatment administration. Sexually active males patients must agree to use condom&#xD;
             during the study and for at least 12 months after the last study treatment&#xD;
             administration. Also, it is recommended their women of childbearing potential partner&#xD;
             use a highly effective method of contraception.&#xD;
&#xD;
          -  In case of previous external beam radiation, all radiation therapy related toxicities&#xD;
             must have resolved to &lt; Grade 2 severity per Common Terminology Criteria for Adverse&#xD;
             Events (CTCAE v 4.0), except alopecia and infertility.&#xD;
&#xD;
          -  Voluntary agreement to provide written informed consent and the willingness and&#xD;
             ability to comply with all aspects of the protocol&#xD;
&#xD;
          -  Patient affiliated to a social security regimen or beneficiary of the same&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Undifferentiated or Medullary (MTC) carcinoma of the thyroid&#xD;
&#xD;
          -  Brain metastases (including asymptomatic brain metastases)&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to the first dose of drug&#xD;
&#xD;
          -  Subjects having &gt; 1 + proteinuria on urine dipstick testing will undergo 24 h urine&#xD;
             collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1&#xD;
             g/24 h will be ineligible.&#xD;
&#xD;
          -  Need for locoregional treatment such as surgery, external beam radiation or&#xD;
             thermoablation at inclusion&#xD;
&#xD;
          -  Prior RAI therapy &lt; 6 months prior initiation of treatment&#xD;
&#xD;
          -  External beam radiation &lt; 4 weeks prior initiation of treatment&#xD;
&#xD;
          -  Iodine contamination defined by a urine ioduria ≥ 50 μg/dl&#xD;
&#xD;
          -  Gastrointestinal malabsorption or any other condition that in the opinion of the&#xD;
             investigator might affect the absorption of the drugs&#xD;
&#xD;
          -  History of congestive heart failure greater or equal to than New York Heart&#xD;
             association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6&#xD;
             months of the first dose of drug, or cardiac arrhythmia associated with significant&#xD;
             cardiovascular impairment and uncontrolled hypertension&#xD;
&#xD;
          -  Electrocardiogram (ECG) with QT interval (QTc) interval ≥480 msec&#xD;
&#xD;
          -  Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 2 months prior to&#xD;
             the first dose of drug and any other active bleeding, coagulopathy or pathologic&#xD;
             condition that would confer a high risk of bleeding.&#xD;
&#xD;
          -  Active infection requiring systemic therapy&#xD;
&#xD;
          -  Active malignancy (except for DTC, or definitively treated melanoma insitu, basal or&#xD;
             squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder)&#xD;
             within the past 24 months&#xD;
&#xD;
          -  Any history of or concomitant medical condition that, in the opinion of the&#xD;
             investigator, would compromise subject's ability to safely complete the protocol&#xD;
&#xD;
          -  Females who are pregnant or breastfeeding&#xD;
&#xD;
          -  Patients with an injection of radio-contrast agent within 8 weeks prior enrolment&#xD;
&#xD;
          -  Previous history of retinal vein occlusion&#xD;
&#xD;
          -  Previous history of central serious retinopathy&#xD;
&#xD;
          -  Known hypersensitivity to the study drugs or to any of the excipients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <state>Val De Marne</state>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>September 27, 2021</last_update_submitted>
  <last_update_submitted_qc>September 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trametinib</mesh_term>
    <mesh_term>Dabrafenib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03244956
org study id: 2017-000742-21
secondary id: 2017/2527
nct id: NCT03244956
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicentric prospective non-randomized phase II trial, with two independent arms:
      one for patients with RAS mutation and one for patients with BRAFV600E mutation.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This is a multicentric prospective non-randomized phase II trial, with two independent arms: one for patients with RAS mutation and one for patients with BRAFV600E mutation
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: Evaluated 6 months after the first dose of trametinib or trametinib and dabrafenib followed by RAI treatment in each arms
description: Propotion of patients with a best overall response of Complete Response (CR) or a Partial Response (PR)
arm group label: patients with RAS mutation
arm group type: Experimental
arm group label: patients with BRAFV600E mutation
arm group type: Experimental
intervention type: Drug
intervention name: Trametinib
description: 2mg daily for a maximum of 6 weeks of treatment
arm group label: patients with BRAFV600E mutation
arm group label: patients with RAS mutation
intervention type: Drug
intervention name: Dabrafenib
description: 150mg twice daily
arm group label: patients with BRAFV600E mutation
intervention type: Radiation
intervention name: 131I
description: 5.5 GBq
arm group label: patients with BRAFV600E mutation
arm group label: patients with RAS mutation
intervention type: Drug
intervention name: rhTSH
description: 0.9mg on two consecutive days after 35 days of treatment
arm group label: patients with BRAFV600E mutation
arm group label: patients with RAS mutation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Thyroid Neoplasms
mesh term: Thyroid Diseases
mesh term: Trametinib
mesh term: Dabrafenib
sharing ipd: Undecided