<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/NCT03808441</url>
  </required_header>
  <id_info>
    <org_study_id>CFTSp129</org_study_id>
    <nct_id>NCT03808441</nct_id>
  </id_info>
  <brief_title>CAcTUS - Circulating Tumour DNA Guided Switch</brief_title>
  <acronym>CAcTUS</acronym>
  <official_title>A Parallel Arm, Biomarker Driven, Phase II Trial to Determine the Role of Circulating Tumour DNA in Guiding a Switch Between Targeted Therapy and Immune Therapy in Patients With Advanced Cutaneous Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Christie NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Manchester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Manchester Academic Health Science Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Christie NHS Foundation Trust</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The stay aims to determine whether switching from targeted therapy to immunotherapy based on&#xD;
      a decrease in levels of circulating tumour DNA in the blood, will improve the outcome in&#xD;
      melanoma patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The optimal scheduling of targeted and immune therapies in metastatic melanoma is unknown. At&#xD;
      present, patients are treated with targeted therapy until acquired resistance develops, and&#xD;
      then switched to immune therapy. Pre-clinical data has revealed that BRAF inhibition results&#xD;
      in an environment that can enhance immune responses. Tumours responding to BRAF inhibitors&#xD;
      but not resistant have been shown to have increased T cell infiltration, improved T cell&#xD;
      recognition of melanoma associated antigens and reduced production of immunosuppressive&#xD;
      cytokines. Furthermore, in response to targeted therapy LDH levels, which are associated with&#xD;
      decreased response to immune therapy reduces, which may improve efficacy of immunotherapy.&#xD;
&#xD;
      A precise definition of response is required in order to decide upon a switch to immune&#xD;
      therapy. A radiological definition of response is currently the standard assessment. However&#xD;
      a scan at a fixed time point of 2 or 3 months does not reflect the wide range of response&#xD;
      dynamics or allow decision making on an individual patient basis. The investigators have&#xD;
      developed techniques using circulating tumour DNA (ctDNA) in the metastatic setting, which&#xD;
      are able to accurately monitor tumour burden over time.&#xD;
&#xD;
      The aim of this pilot study is to provide a signal as to whether:&#xD;
&#xD;
        1. In BRAF mutant melanoma the efficacy of immune therapy is enhanced by response to&#xD;
           pre-treatment with MAPK pathway inhibition with dabrafenib + trametinib.&#xD;
&#xD;
        2. Changes in ctDNA levels can be used to accurately inform when to switch from targeted to&#xD;
           immune therapy.&#xD;
&#xD;
      Data from this study will provide the basis for follow on studies with sufficient power to&#xD;
      assess whether tumours responding to BRAF inhibition as defined by response in ctDNA can&#xD;
      improve efficacy of immune therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 2, 2019</start_date>
  <completion_date type="Anticipated">May 2, 2024</completion_date>
  <primary_completion_date type="Actual">April 26, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>CtDNA result critical (red) blood samples returned within 7 working days of samples being received in the laboratory</measure>
    <time_frame>12 months from last patient starting trial treatment</time_frame>
    <description>Feasibility of returning samples to hospitals from the laboratory to inform clinical decisions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Decrease in ctDNA level of mutant BRAF≥80%</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>To assess whether a decrease in ctDNA levels of mutant BRAF by ≥80% on targeted therapy is an appropriate cut off for switching to immune therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Screen failure due to ctDNA levels of mutant BRAF VAF &lt;1.5% Efficacy</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>To assess whether BRAF VAF (within the ctDNA) of ≥1.5% is an appropriate target for study inclusion (by assessing the number and proportion of screen failures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>First progression free survival (PFS) at 12 months</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>To explore whether PFS at 12 months would improve in patients switching from targeted to immune therapy on response to treatment as guided by ctDNA levels of mutant BRAF VAF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>First progression free survival</measure>
    <time_frame>When all patients finished follow up, 4 years after last patient starting treatment</time_frame>
    <description>Time to first progression in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Second progression free survival</measure>
    <time_frame>When all patients finished follow up, 4 years after last patient starting treatment</time_frame>
    <description>Time to second progression in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>When all patients finished follow up, 4 years after last patient starting treatment</time_frame>
    <description>Explore whether survival outcomes would improve in patients switching from targeted to immune therapy on response to treatment as guided by ctDNA levels of mutant BRAF VAF</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Time to ctDNA first progression</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Time to first progression measured by ctDNA</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to ctDNA second progression</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Time to second progression measured by ctDNA</description>
  </other_outcome>
  <other_outcome>
    <measure>Increase in ctDNA levels of BRAF VAF during washout period from targeted to immune therapy switch in arm B</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Duration of mutant BRAF VAF (within ctDNA) response to targeted therapy</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Duration of mutant BRAF VAF (within ctDNA) response to immune therapy</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time between observing rise in ctDNA levels of mutant BRAF VAF and progressive disease observed on scheduled scan</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
    <description>To explore the relationship between observing a rise in ctDNA level of mutant BRAF VAF and progressive disease observed from scheduled scan results</description>
  </other_outcome>
  <other_outcome>
    <measure>Time taken for mutant ctDNA level of mutant BRAF VAF to reach ≥80% decrease on targeted therapy</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
    <description>To compare duration in ctDNA level of mutant BRAF VAF response to targeted therapy between study arms</description>
  </other_outcome>
  <other_outcome>
    <measure>ctDNA level of mutant BRAF VAF (at each follow-up assessment timepoint)</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
    <description>To compare duration in ctDNA level of mutant BRAF VAF (within ctDNA) response to immune therapy between study arms</description>
  </other_outcome>
  <other_outcome>
    <measure>Best overall response rate to immune therapy</measure>
    <time_frame>hen all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
    <description>To explore whether switching from targeted to immune therapy on treatment response as guided by ctDNA levels of mutant BRAF VAF will increase response to therapy</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of response to immune therapy</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Progression free survival on immune therapy from date of commencement of immune therapy</measure>
    <time_frame>When all patients finished treatment, an average of 1 year after last patient starting treatment</time_frame>
    <description>Time to progression on immune therapy</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Standard Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Dabrafenib + Trametinib&#xD;
Switch to N+I at first progression</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ctDNA Guided Switch</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dabrafenib + Trametinib&#xD;
Switch to N+I when ctDNA levels in the blood have dropped by ≥80%.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ctDNA analysis</intervention_name>
    <description>Regular ctDNA analysis, which upon a decrease in mutant BRAF VAF (variant allele frequency) level of ≥80% the switch to N+I is triggered.</description>
    <arm_group_label>ctDNA Guided Switch</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient capable of giving written informed consent&#xD;
&#xD;
          2. Patients must be willing and able to comply with scheduled visits, treatment schedule,&#xD;
             laboratory tests and other requirements of the study.&#xD;
&#xD;
          3. Histological confirmation of cutaneous melanoma&#xD;
&#xD;
          4. ≥ 16 years&#xD;
&#xD;
          5. Stage III un-resectable/ IV disease&#xD;
&#xD;
          6. BRAF p.V600E/K/R mutation confirmed (exact point mutation must be provided to the&#xD;
             investigators)&#xD;
&#xD;
          7. At least one target lesion measurable by CT or MRI as per RECIST 1.1&#xD;
&#xD;
          8. Baseline ctDNA (as defined by the mutant BRAF VAF in plasma) ≥1.5%&#xD;
&#xD;
          9. Adequate organ function&#xD;
&#xD;
         10. ECOG performance status 0/1&#xD;
&#xD;
         11. Prior radiotherapy or radiosurgery must have been completed at least 2 weeks prior to&#xD;
             the first dose of study drug&#xD;
&#xD;
         12. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy&#xD;
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to&#xD;
             the start of study drug.&#xD;
&#xD;
         13. WOCBP must agree to follow instructions for method(s) of contraception for the&#xD;
             duration of treatment with study drugs plus 5 half-lives of the drugs they are taking&#xD;
             at treatment completion (5 times the half-life = 125 days [nivolumab]; 5 times the&#xD;
             half-life = 90 days [ipilimumab]; 5 times the half life = 40 hours [dabrafenib]; 5&#xD;
             times the half life = 50 days [trametinib]) plus 30 days (duration of ovulatory&#xD;
             cycle).&#xD;
&#xD;
         14. Males who are sexually active with WOCBP must agree to follow instructions for&#xD;
             method(s) of contraception for the duration of treatment plus 5 half-lives of the&#xD;
             study drug as above plus 90 days (duration of sperm turnover).&#xD;
&#xD;
         15. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt&#xD;
             from contraceptive requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior systemic anti-cancer treatment (immune therapy, targeted therapy, vaccine&#xD;
             therapy, or investigational treatment) for unresectable Stage III or Stage IV&#xD;
             melanoma.&#xD;
&#xD;
          2. Prior adjuvant therapy with BRAF +/- MEK inhibitor or adjuvant therapy with&#xD;
             combination PD-1 inhibitor plus CTLA-4 inhibitor. Prior adjuvant therapy with PD-1&#xD;
             inhibitor is allowed so long as relapse occurred &gt; 6 months from discontinuation of&#xD;
             treatment and treatment not stopped due to grade 3 or 4 toxicity.&#xD;
&#xD;
          3. Current use of a prohibited medication&#xD;
&#xD;
          4. History of another malignancy. Exception: patients who have been disease-free for 3&#xD;
             years, (i.e. patients with second malignancies that are indolent or definitively&#xD;
             treated at least 3 years ago) or patients with a history of completely resected&#xD;
             non-melanoma skin cancer. No additional therapy should be required whilst the patient&#xD;
             is on study.&#xD;
&#xD;
          5. Any serious or unstable pre-existing medical conditions (aside from malignancy&#xD;
             exceptions specified above), psychiatric disorders, or other conditions that could&#xD;
             interfere with the patients safety, obtaining informed consent, or compliance with&#xD;
             study procedures.&#xD;
&#xD;
          6. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C&#xD;
             Virus (HCV) infection (patients with laboratory evidence of cleared or chronic (not&#xD;
             active) HBV and HCV infection will be permitted).&#xD;
&#xD;
          7. A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.&#xD;
&#xD;
          8. Patients with active, known or suspected autoimmune disease. Patients with type 1&#xD;
             diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders&#xD;
             (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or&#xD;
             conditions not expected to recur in the absence of an external trigger will be&#xD;
             permitted to enrol.&#xD;
&#xD;
          9. Patients with a condition requiring systemic treatment with either corticosteroids&#xD;
             (&gt;10 mg daily prednisone equivalent) or other immunosuppressive medications within 14&#xD;
             days of study drug administration. Inhaled or topical steroids and adrenal replacement&#xD;
             steroid doses &gt; 10 mg daily prednisone equivalent are permitted in the absence of&#xD;
             active autoimmune disease.&#xD;
&#xD;
         10. Patients with interstitial lung disease that is symptomatic or may interfere with the&#xD;
             detection or management of suspected drug-related pulmonary toxicity.&#xD;
&#xD;
         11. Brain metastases and leptomeningeal metastases are excluded unless:&#xD;
&#xD;
               -  Asymptomatic and untreated at presentation, OR&#xD;
&#xD;
               -  Symptomatic lesions have been definitively treated with surgery or stereotactic&#xD;
                  surgery (whole-brain radiation may be given as adjuvant treatment), and do not&#xD;
                  require steroids for control of symptoms&#xD;
&#xD;
               -  Symptomatic metastases, treated or untreated, or metastases requiring steroids to&#xD;
                  control symptoms, are excluded&#xD;
&#xD;
         12. No enzyme inducing anticonvulsants for ≥ 4 weeks prior to randomisation&#xD;
&#xD;
         13. Coronary syndromes (including myocardial infarction within 6 months or unstable&#xD;
             angina)&#xD;
&#xD;
         14. A history or evidence of current ≥ Class II congestive heart failure as defined by the&#xD;
             New York Heart Association (NYHA) guidelines with an ejection fraction of &lt;50%&#xD;
&#xD;
         15. Treatment refractory hypertension defined as a blood pressure of systolic&gt; 150 mmHg&#xD;
             and/or diastolic &gt; 95 mm Hg on &gt;3 occasions which cannot be controlled by&#xD;
             anti-hypertensive therapy;&#xD;
&#xD;
         16. Known cardiac metastases;&#xD;
&#xD;
         17. Uncorrectable electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia,&#xD;
             hypocalcaemia), long QT syndrome or taking medicinal products known to prolong the QT&#xD;
             interval.&#xD;
&#xD;
         18. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous&#xD;
             retinopathy (CSR) including presence of predisposing factors to RVO or CSR (e.g.,&#xD;
             uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled&#xD;
             diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes)&#xD;
&#xD;
         19. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs&#xD;
             chemically related to the study treatments including monoclonal antibodies, their&#xD;
             excipients, and/or dimethyl sulfoxide (DMSO) and/or Polysorbate-80-containing&#xD;
             infusions.&#xD;
&#xD;
         20. Females who are breast-feeding.&#xD;
&#xD;
         21. Prisoners or patients who are involuntarily incarcerated.&#xD;
&#xD;
         22. Patients who are compulsorily detained for treatment of either a psychiatric or&#xD;
             physical (e.g., infectious disease) illness.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Lorigan</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Christie National Health Service (NHS) Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 7, 2018</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>August 23, 2023</last_update_submitted>
  <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Circulating tumour DNA</keyword>
  <keyword>targeted therapy</keyword>
  <keyword>immune therapy</keyword>
  <keyword>dabrafenib</keyword>
  <keyword>trametinib</keyword>
  <keyword>ipilimumab</keyword>
  <keyword>nivolumab</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/NCT03808441
org study id: CFTSp129
nct id: NCT03808441
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The stay aims to determine whether switching from targeted therapy to immunotherapy based on
      a decrease in levels of circulating tumour DNA in the blood, will improve the outcome in
      melanoma patients.
The optimal scheduling of targeted and immune therapies in metastatic melanoma is unknown. At
      present, patients are treated with targeted therapy until acquired resistance develops, and
      then switched to immune therapy. Pre-clinical data has revealed that BRAF inhibition results
      in an environment that can enhance immune responses. Tumours responding to BRAF inhibitors
      but not resistant have been shown to have increased T cell infiltration, improved T cell
      recognition of melanoma associated antigens and reduced production of immunosuppressive
      cytokines. Furthermore, in response to targeted therapy LDH levels, which are associated with
      decreased response to immune therapy reduces, which may improve efficacy of immunotherapy.

      A precise definition of response is required in order to decide upon a switch to immune
      therapy. A radiological definition of response is currently the standard assessment. However
      a scan at a fixed time point of 2 or 3 months does not reflect the wide range of response
      dynamics or allow decision making on an individual patient basis. The investigators have
      developed techniques using circulating tumour DNA (ctDNA) in the metastatic setting, which
      are able to accurately monitor tumour burden over time.

      The aim of this pilot study is to provide a signal as to whether:

        1. In BRAF mutant melanoma the efficacy of immune therapy is enhanced by response to
           pre-treatment with MAPK pathway inhibition with dabrafenib + trametinib.

        2. Changes in ctDNA levels can be used to accurately inform when to switch from targeted to
           immune therapy.

      Data from this study will provide the basis for follow on studies with sufficient power to
      assess whether tumours responding to BRAF inhibition as defined by response in ctDNA can
      improve efficacy of immune therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: CtDNA result critical (red) blood samples returned within 7 working days of samples being received in the laboratory
time frame: 12 months from last patient starting trial treatment
description: Feasibility of returning samples to hospitals from the laboratory to inform clinical decisions
measure: Decrease in ctDNA level of mutant BRAF≥80%
time frame: Through study completion, an average of 1 year
description: To assess whether a decrease in ctDNA levels of mutant BRAF by ≥80% on targeted therapy is an appropriate cut off for switching to immune therapy
measure: Screen failure due to ctDNA levels of mutant BRAF VAF <1.5% Efficacy
time frame: Through study completion, an average of 1 year
description: To assess whether BRAF VAF (within the ctDNA) of ≥1.5% is an appropriate target for study inclusion (by assessing the number and proportion of screen failures
measure: First progression free survival (PFS) at 12 months
time frame: Through study completion, an average of 1 year
description: To explore whether PFS at 12 months would improve in patients switching from targeted to immune therapy on response to treatment as guided by ctDNA levels of mutant BRAF VAF
measure: First progression free survival
time frame: When all patients finished follow up, 4 years after last patient starting treatment
description: Time to first progression in both arms
measure: Second progression free survival
time frame: When all patients finished follow up, 4 years after last patient starting treatment
description: Time to second progression in both arms
measure: Overall survival
time frame: When all patients finished follow up, 4 years after last patient starting treatment
description: Explore whether survival outcomes would improve in patients switching from targeted to immune therapy on response to treatment as guided by ctDNA levels of mutant BRAF VAF
measure: Time to ctDNA first progression
time frame: Through study completion, an average of 1 year
description: Time to first progression measured by ctDNA
measure: Time to ctDNA second progression
time frame: Through study completion, an average of 1 year
description: Time to second progression measured by ctDNA
measure: Increase in ctDNA levels of BRAF VAF during washout period from targeted to immune therapy switch in arm B
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
measure: Duration of mutant BRAF VAF (within ctDNA) response to targeted therapy
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
measure: Duration of mutant BRAF VAF (within ctDNA) response to immune therapy
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
measure: Time between observing rise in ctDNA levels of mutant BRAF VAF and progressive disease observed on scheduled scan
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
description: To explore the relationship between observing a rise in ctDNA level of mutant BRAF VAF and progressive disease observed from scheduled scan results
measure: Time taken for mutant ctDNA level of mutant BRAF VAF to reach ≥80% decrease on targeted therapy
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
description: To compare duration in ctDNA level of mutant BRAF VAF response to targeted therapy between study arms
measure: ctDNA level of mutant BRAF VAF (at each follow-up assessment timepoint)
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
description: To compare duration in ctDNA level of mutant BRAF VAF (within ctDNA) response to immune therapy between study arms
measure: Best overall response rate to immune therapy
time frame: hen all patients finished treatment, an average of 1 year after last patient starting treatment
description: To explore whether switching from targeted to immune therapy on treatment response as guided by ctDNA levels of mutant BRAF VAF will increase response to therapy
measure: Duration of response to immune therapy
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
measure: Progression free survival on immune therapy from date of commencement of immune therapy
time frame: When all patients finished treatment, an average of 1 year after last patient starting treatment
description: Time to progression on immune therapy
arm group label: Standard Arm
arm group type: No Intervention
description: Dabrafenib + Trametinib
Switch to N+I at first progression
arm group label: ctDNA Guided Switch
arm group type: Active Comparator
description: Dabrafenib + Trametinib
Switch to N+I when ctDNA levels in the blood have dropped by ≥80%.
intervention type: Other
intervention name: ctDNA analysis
description: Regular ctDNA analysis, which upon a decrease in mutant BRAF VAF (variant allele frequency) level of ≥80% the switch to N+I is triggered.
arm group label: ctDNA Guided Switch
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Paul Lorigan
role: Principal Investigator
affiliation: The Christie National Health Service (NHS) Foundation Trust
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: No