<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/NCT02974803</url>
  </required_header>
  <id_info>
    <org_study_id>I224</org_study_id>
    <nct_id>NCT02974803</nct_id>
  </id_info>
  <brief_title>Concurrent Dabrafenib + Trametinib With Sterotactic Radiation in BRAF Mutation-Positive Malignant Melanoma and Brain Metastases</brief_title>
  <official_title>A Phase II Study of Concurrent Dabrafenib and Trametinib With Stereotactic Radiation in the Management of Patients With BRAF Mutation-Positive Malignant Melanoma and Brain Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Canadian Cancer Trials Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Canadian Cancer Trials Group</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>
      Dabrafenib and trametinib are drugs that are usually given for the treatment of melanoma.&#xD;
      Combinations of dabrafenib and trametinib have also been studied and when used together have&#xD;
      shown to increase tumour shrinkage in animals compared to either drug alone. Dabrafenib and&#xD;
      trametinib have also shown potential to penetrate the blood-brain-barrier when given together&#xD;
      and have an effect on brain metastases. Giving these drugs at the same time and then giving&#xD;
      brain stereotactic radiosurgery (SRS) may also be preferred in patients with brain metastases&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to find out the effects of giving dabrafenib in combination with&#xD;
      trametinib continuously with stereotactic radiotherapy (SRS) has on melanoma and brain&#xD;
      metastases.&#xD;
&#xD;
      Stereotactic Radiosurgery (SRS) is a non-surgical radiation therapy used to treat tumours of&#xD;
      the brain. It can deliver precisely targeted radiation. Currently SRS alone is the usual&#xD;
      treatment for patients with up to 4 brain lesions. This study will include 2 groups 1)&#xD;
      patients with 1-4 brain lesions treated with SRS concurrently with dabrafenib and trametinib&#xD;
      and 2) patients with 5-10 brain lesions treated with SRS concurrently with dabrafenib and&#xD;
      trametinib.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Very slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">February 9, 2018</start_date>
  <completion_date type="Actual">July 29, 2020</completion_date>
  <primary_completion_date type="Actual">July 29, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intracranial Objective Response Rate</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Extra-cranial Objective Response Rate</measure>
    <time_frame>24 months</time_frame>
    <description>Response will be assessed using RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>24 months</time_frame>
    <description>Response will be assessed using RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial Progression Free Survival</measure>
    <time_frame>24 months</time_frame>
    <description>Response will be assessed using RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Progression Free Survival</measure>
    <time_frame>24 months</time_frame>
    <description>Response will be assessed using RECIST v1.1</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Overall Objective Response Rate</measure>
    <time_frame>24 months</time_frame>
    <description>Response will be assessed using RECIST v1.1</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Melanoma</condition>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>Dabrafenib and Trametinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabrafenib</intervention_name>
    <description>Dabrafenib 150 mg twice a day until progression or unaccepted toxicity.</description>
    <arm_group_label>Dabrafenib and Trametinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib</intervention_name>
    <description>Trametinib 2 mg once daily until progression or unaccepted toxicity.</description>
    <arm_group_label>Dabrafenib and Trametinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed melanoma metastatic to brain and determined to be BRAF V600&#xD;
             mutated.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Karnofsky Performance Status of 70-100 (Appendix I).&#xD;
&#xD;
          -  Patients must have a life expectancy of at least 12 weeks.&#xD;
&#xD;
          -  Presence of measurable disease (i.e. present with at least one measurable CNS lesion&#xD;
             per RECIST 1.1).&#xD;
&#xD;
          -  Presence of 1-10 brain metastases as confirmed on a thin slice axial T1&#xD;
             post-gadolinium MRI sequence. The maximum diameter of a single brain lesion should be&#xD;
             ≤ 4 cm and presence of a measurable lesion ≥ 1cm based on baseline MRI of brain.&#xD;
&#xD;
          -  All CNS metastases amenable to single fraction SRS and or fractionated SRS.&#xD;
             Hemorrhagic lesions are allowed if the treating radiation oncologist deems the lesion&#xD;
             amenable to focal SRS.&#xD;
&#xD;
          -  Able to swallow and retain oral medication and must not have any clinically&#xD;
             significant gastrointestinal abnormalities that may alter absorption such as&#xD;
             malabsorption syndrome or major resection of the stomach or bowels.&#xD;
&#xD;
          -  Laboratory requirements (within 14 days prior to registration):&#xD;
&#xD;
               -  ANC ≥ 1.2 x 10^9/L&#xD;
&#xD;
               -  Hemoglobin ≥ 90 g/L&#xD;
&#xD;
               -  Platelet count ≥ 100 x 10^9/L&#xD;
&#xD;
               -  PT/INR &amp; PTT ≤ 1.3 x ULN&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               -  AST and ALT ≤ 2.5 x ULN&#xD;
&#xD;
               -  Serum creatinine or ≤ 1.5 x ULN or Creatinine Clearance ≥ 50 ml/min (calculated&#xD;
                  by Cockcroft and Gault)&#xD;
&#xD;
               -  LVEF ≥ LLN (within 28 days prior to registration)&#xD;
&#xD;
               -  No prior treatment with a BRAF inhibitor or MEK inhibitor.&#xD;
&#xD;
               -  No known ocular or primary mucosal melanoma.&#xD;
&#xD;
               -  No prior systemic anti-cancer treatment within the last 2 weeks preceding the&#xD;
                  frist dose of dabrafenib and trametinib. Patients must have recoved from clinical&#xD;
                  manifestations of toxicity related to prior systemic therapy and have adequate&#xD;
                  washout as follows: Longest of one of the following:&#xD;
&#xD;
                    -  two weeks&#xD;
&#xD;
                    -  5 half-lives for investigational agents&#xD;
&#xD;
                    -  Standard cycle length of standard therapies&#xD;
&#xD;
               -  Prior systemic treatment in the adjuvant setting is allowed.&#xD;
&#xD;
               -  No current use of a prohibited medication as described in section 7.2.&#xD;
&#xD;
               -  No history of malignancy with confirmed activating RAS mutation at any time.&#xD;
&#xD;
               -  No history of malignancy other than disease under study within 3 years of study&#xD;
                  enrollment.&#xD;
&#xD;
               -  No leptomeningeal metastases or metastases causing spinal cord compression that&#xD;
                  are symptomatic or untreated or not stable for ≥ 3 months. Subjects on stable&#xD;
                  dose of corticosteroids &gt; 2 weeks or who have been off of corticosteroids for at&#xD;
                  least 2 weeks can be enrolled with approval of CCTG.&#xD;
&#xD;
               -  No serious or unstable pre-existing medical conditions, psychiatric disorders or&#xD;
                  other conditions that could interfere with the subject's safety, obtaining&#xD;
                  informed consent or compliance with study procedures.&#xD;
&#xD;
               -  No history of Hepatitis B Virus or Hepatitis C Virus infection&#xD;
&#xD;
               -  No history or evidence of cardiovascular risk No history or current&#xD;
                  eveidence/risk of retinal vein occlusion or central serous retinopathy&#xD;
&#xD;
               -  No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs&#xD;
                  chemically related to the study treatments, their excipients, and/or dimethyl&#xD;
                  sulfoxide.&#xD;
&#xD;
               -  No pregnant or lactating women.&#xD;
&#xD;
               -  No hisotry of interstitial lung disease or active pneumonitis.&#xD;
&#xD;
               -  Presence of any one brain metastases &gt;4cm in maximal diameter, and/or presence of&#xD;
                  brain metastase of less than 1cm.&#xD;
&#xD;
               -  No prior whole brain radiation&#xD;
&#xD;
               -  No brainstem metastses&#xD;
&#xD;
               -  No contrindications to MRI and/or Gadolinimum contrast or sterotactic brain&#xD;
                  radiation therapy.&#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>Arjun Sahgal</last_name>
    <role>Study Chair</role>
    <affiliation>Odette Cancer Centre, Toronto, ON Canada</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Teresa Petrella</last_name>
    <role>Study Chair</role>
    <affiliation>Odette Cancer Centre, Toronto, ON Canada</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>QEII Health Sciences Centre</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 1V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juravinski Cancer Centre at Hamilton Health Sciences</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odette Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier universitaire de Sherbrooke</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saskatoon Cancer Centre</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <zip>S7N 4H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2016</study_first_posted>
  <results_first_submitted>May 5, 2021</results_first_submitted>
  <results_first_submitted_qc>July 22, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 17, 2021</results_first_posted>
  <last_update_submitted>August 18, 2021</last_update_submitted>
  <last_update_submitted_qc>August 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 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>Melanoma</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</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>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT02974803/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dabrafenib and Trametinib</title>
          <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dabrafenib and Trametinib</title>
          <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63" lower_limit="27" upper_limit="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Intracranial Objective Response Rate</title>
        <time_frame>24 months</time_frame>
        <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabrafenib and Trametinib</title>
            <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
          </group>
        </group_list>
        <measure>
          <title>Intracranial Objective Response Rate</title>
          <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Extra-cranial Objective Response Rate</title>
        <description>Response will be assessed using RECIST v1.1</description>
        <time_frame>24 months</time_frame>
        <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabrafenib and Trametinib</title>
            <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
          </group>
        </group_list>
        <measure>
          <title>Extra-cranial Objective Response Rate</title>
          <description>Response will be assessed using RECIST v1.1</description>
          <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Response will be assessed using RECIST v1.1</description>
        <time_frame>24 months</time_frame>
        <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabrafenib and Trametinib</title>
            <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Response will be assessed using RECIST v1.1</description>
          <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intracranial Progression Free Survival</title>
        <description>Response will be assessed using RECIST v1.1</description>
        <time_frame>24 months</time_frame>
        <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabrafenib and Trametinib</title>
            <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
          </group>
        </group_list>
        <measure>
          <title>Intracranial Progression Free Survival</title>
          <description>Response will be assessed using RECIST v1.1</description>
          <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Progression Free Survival</title>
        <description>Response will be assessed using RECIST v1.1</description>
        <time_frame>24 months</time_frame>
        <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabrafenib and Trametinib</title>
            <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Progression Free Survival</title>
          <description>Response will be assessed using RECIST v1.1</description>
          <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Overall Objective Response Rate</title>
        <description>Response will be assessed using RECIST v1.1</description>
        <time_frame>24 months</time_frame>
        <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabrafenib and Trametinib</title>
            <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Objective Response Rate</title>
          <description>Response will be assessed using RECIST v1.1</description>
          <population>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 months</time_frame>
      <desc>The study was closed early because of very slow accrual and no final analysis was performed because the collected data cannot be considered reliable since they were not verified, reviewed or cleaned.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dabrafenib and Trametinib</title>
          <description>Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously&#xD;
Dabrafenib&#xD;
Trametinib</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Lesely Seymour</name_or_title>
      <organization>Canadian Cancer Trials Group</organization>
      <phone>6135336430</phone>
      <email>lseymour@ctg.queensu.ca</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02974803
org study id: I224
nct id: NCT02974803
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Dabrafenib and trametinib are drugs that are usually given for the treatment of melanoma.
      Combinations of dabrafenib and trametinib have also been studied and when used together have
      shown to increase tumour shrinkage in animals compared to either drug alone. Dabrafenib and
      trametinib have also shown potential to penetrate the blood-brain-barrier when given together
      and have an effect on brain metastases. Giving these drugs at the same time and then giving
      brain stereotactic radiosurgery (SRS) may also be preferred in patients with brain metastases
The purpose of this study is to find out the effects of giving dabrafenib in combination with
      trametinib continuously with stereotactic radiotherapy (SRS) has on melanoma and brain
      metastases.

      Stereotactic Radiosurgery (SRS) is a non-surgical radiation therapy used to treat tumours of
      the brain. It can deliver precisely targeted radiation. Currently SRS alone is the usual
      treatment for patients with up to 4 brain lesions. This study will include 2 groups 1)
      patients with 1-4 brain lesions treated with SRS concurrently with dabrafenib and trametinib
      and 2) patients with 5-10 brain lesions treated with SRS concurrently with dabrafenib and
      trametinib.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Intracranial Objective Response Rate
time frame: 24 months
measure: Extra-cranial Objective Response Rate
time frame: 24 months
description: Response will be assessed using RECIST v1.1
measure: Duration of Response
time frame: 24 months
description: Response will be assessed using RECIST v1.1
measure: Intracranial Progression Free Survival
time frame: 24 months
description: Response will be assessed using RECIST v1.1
measure: Overall Progression Free Survival
time frame: 24 months
description: Response will be assessed using RECIST v1.1
measure: Overall Objective Response Rate
time frame: 24 months
description: Response will be assessed using RECIST v1.1
arm group label: Dabrafenib and Trametinib
arm group type: Experimental
description: Dabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously
intervention type: Drug
intervention name: Dabrafenib
description: Dabrafenib 150 mg twice a day until progression or unaccepted toxicity.
arm group label: Dabrafenib and Trametinib
intervention type: Drug
intervention name: Trametinib
description: Trametinib 2 mg once daily until progression or unaccepted toxicity.
arm group label: Dabrafenib and Trametinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Arjun Sahgal
role: Study Chair
affiliation: Odette Cancer Centre, Toronto, ON Canada
last name: Teresa Petrella
role: Study Chair
affiliation: Odette Cancer Centre, Toronto, ON Canada
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Trametinib
mesh term: Dabrafenib
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 