<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/NCT03256981</url>
  </required_header>
  <id_info>
    <org_study_id>ICR-CTSU/2016/10061</org_study_id>
    <nct_id>NCT03256981</nct_id>
  </id_info>
  <brief_title>Stereotactic Body Radiotherapy for the Treatment of OPD</brief_title>
  <acronym>HALT</acronym>
  <official_title>Targeted Therapy With or Without Dose Intensified Radiotherapy for Oligo-progressive Disease in Oncogene-addicted Lung Tumours</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Cancer Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Cancer Research, United Kingdom</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>
      HALT is a phase II, randomised multi-centre study with integrated seamless continuation to&#xD;
      phase III trial following acceptable safety and feasibility assessment.&#xD;
&#xD;
      HALT aims to recruit 110 patients with mutation positive advanced NSCLC with oligoprogressive&#xD;
      disease (OPD) following initial response to a Tyrosine Kinase Inhibitor (TKI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will be randomised to receive either SBRT or no SBRT at a ratio of 2:1&#xD;
      (SBRT : no SBRT), with all patients continuing to receive background treatment with TKI&#xD;
      therapy as clinically indicated and as per standard care. Patients randomised to receive SBRT&#xD;
      will receive a dose and fractionation schedule dependent on OPD lesion site and proximity to&#xD;
      critical normal tissues. All patients will be seen 8 weeks post randomisation, then 3 monthly&#xD;
      in line with routine care.&#xD;
&#xD;
      HALT aims to assess whether in patients with mutation positive advanced NSCLC the use of SBRT&#xD;
      to ≤ 3 sites of OPD with continuation of TKI improves progression-free survival (PFS)&#xD;
      compared with continuation of TKI alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 27, 2017</start_date>
  <completion_date type="Anticipated">November 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Time from randomisation to the first of one of the above events or death. Assessed 8 weeks post-randomisation and 3-monthly thereafter (up to 24 months)</time_frame>
    <description>The primary outcome measure is progression free survival defined as the time from randomisation to the first of one of the following events or death from any cause:&#xD;
Clinically symptomatic progression requiring palliative tumour-specific oncological intervention (e.g. change in systemic therapy or localised non-SBRT radiotherapy) as determined by the treating physician.&#xD;
New or existing intra-cranial lesions not amenable to radical surgery or Stereotactic radiosurgery (SRS).&#xD;
Development of new extra-cranial lesions or progression of existing extra-cranial lesions not meeting the criteria for&#xD;
SBRT treatment (e.g. size &gt;5cm)&#xD;
Development of &gt;3 new or progressing extra-cranial lesion at any one point in time (i.e. widespread progression)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to next line of systemic therapy or palliative care</measure>
    <time_frame>Time from randomisation to change in therapy or referral to palliative care due to clinical progression as determined by the treating physician, or death. Assessed 3-monthly until progression and 6-monthly thereafter (up to 24 months).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Time from randomisation until death from any cause. Assessed up to 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patterns of disease progression identified from CT scans to further document natural history of oncogene-addicted NSCLC</measure>
    <time_frame>Assessed 3-monthly up to 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiotherapy toxicities (acute events)</measure>
    <time_frame>Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).</time_frame>
    <description>Acute events are defined as ≤ 90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant) assessed using CTCAE v4.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiotherapy toxicities (late events)</measure>
    <time_frame>Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).</time_frame>
    <description>Late events are defined as &gt; 90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant) assessed using RTOG.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (EQ-5D-5L)</measure>
    <time_frame>Baseline, 8 weeks and at the first 3 month visit.</time_frame>
    <description>Assessed using EQ-5D-5L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (EORTC QLQ-C30)</measure>
    <time_frame>Baseline, 8 weeks and at the first 3 month visit.</time_frame>
    <description>Assessed using EORTC QLQ-C30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of resistant sub-clones in Circulating tumour DNA (ctDNA)</measure>
    <time_frame>Baseline, 8 weeks post-randomisation and 3-monthly intervals during follow-up (up to 24 months).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to failure of next line treatment</measure>
    <time_frame>Time from randomisation to disease progression on next line of active systemic therapy. Assessed up to 24 months.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">110</enrollment>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>SBRT and continued TKI therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will continue to receive background TKI treatment as prior to trial entry.&#xD;
Simultaneous administration (SBRT &amp; TKI) or break in TKI during SBRT will be by centre preference and determined prior to commencing recruitment.&#xD;
Repeat SBRT will be permissible upon development of subsequent OPD lesions dependent on SBRT suitability and total progression lesion number at any one point remaining ≤ 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continued TKI therapy alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuation on the same background TKI treatment as prior to trial entry</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SBRT</intervention_name>
    <description>SBRT dose and fractionation dependent on site of metastasis and proximity to critical normal tissues.</description>
    <arm_group_label>SBRT and continued TKI therapy</arm_group_label>
    <other_name>Stereotactic body radiotherapy</other_name>
    <other_name>SABR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TKI</intervention_name>
    <description>Continued background TKI alone</description>
    <arm_group_label>Continued TKI therapy alone</arm_group_label>
    <other_name>Tyrosine Kinase Inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, ≥ 16 years of age&#xD;
&#xD;
          2. Established histological diagnosis of advanced NSCLC, not suitable for radical&#xD;
             treatment, with defined actionable mutation receiving targeted TKI therapy&#xD;
&#xD;
          3. Clinical and/or radiologically confirmed response to TKI therapy (assessed locally&#xD;
             usually 2-3 months post commencing TKI)&#xD;
&#xD;
          4. Confirmed OPD defined as ≤ 3 extracranial sites of progressive disease. All sites must&#xD;
             be visible, imaging defined targets and suitable for treatment with SBRT as determined&#xD;
             by the virtual multi-disciplinary team (MDT) and in accordance with the HALT&#xD;
             Radiotherapy planning and delivery guidance document.&#xD;
&#xD;
          5. Adequate baseline organ function to allow SBRT to all relevant targets&#xD;
&#xD;
          6. Predicted life expectancy ≥ 6 months&#xD;
&#xD;
          7. Karnofsky Index ≥ 60% and ECOG 0-2&#xD;
&#xD;
          8. Provision of written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. &gt; 3 extracranial sites of progressive disease&#xD;
&#xD;
          2. Progressing or newly diagnosed brain metastases not amenable to radical surgery or&#xD;
             SRS. Treated brain metastases which have remained clinically and radiologically stable&#xD;
             for ≥ 6 months are permissible.&#xD;
&#xD;
          3. Prior radiotherapy near the oligoprogressive lesion precluding ablative SBRT.&#xD;
             Suitability of lesions for ablative SBRT as part of the trial defined in section 4.1&#xD;
             of this document and will be determined by the HALT virtual MDT&#xD;
&#xD;
          4. Co-morbidities considered clinically precluding the safe use of SBRT (as detailed in&#xD;
             the HALT radiotherapy planning and delivery guidelines).&#xD;
&#xD;
          5. Any psychological, sociological or geographical issue potentially hampering compliance&#xD;
             with the study&#xD;
&#xD;
          6. Pregnancy&#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>Fiona McDonald, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Marsden NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>HALT Trial Manager</last_name>
    <phone>+442087224554</phone>
    <email>halt-icrctsu@icr.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Royal Marsden Hosital</name>
      <address>
        <city>Sutton</city>
        <state>England</state>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Fiona McDonald</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital</name>
      <address>
        <city>Chelsea</city>
        <state>London</state>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Fiona McDonald</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Surrey County Hospital</name>
      <address>
        <city>Guildford</city>
        <state>Surrey</state>
        <zip>GU2 7XX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Veni Ezhil</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Christie Hospital</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Corinne Faivre-Finn</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nottingham City Hospital</name>
      <address>
        <city>Nottingham</city>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Abigail Pascoe</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Weston Park Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2SJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Caroline Lee</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>October 19, 2018</last_update_submitted>
  <last_update_submitted_qc>October 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SBRT</keyword>
  <keyword>Oligoprogressive disease</keyword>
  <keyword>NSCLC</keyword>
  <keyword>TKI</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tyrosine Protein Kinase Inhibitors</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03256981
org study id: ICR-CTSU/2016/10061
nct id: NCT03256981
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
HALT is a phase II, randomised multi-centre study with integrated seamless continuation to
      phase III trial following acceptable safety and feasibility assessment.

      HALT aims to recruit 110 patients with mutation positive advanced NSCLC with oligoprogressive
      disease (OPD) following initial response to a Tyrosine Kinase Inhibitor (TKI).
Eligible patients will be randomised to receive either SBRT or no SBRT at a ratio of 2:1
      (SBRT : no SBRT), with all patients continuing to receive background treatment with TKI
      therapy as clinically indicated and as per standard care. Patients randomised to receive SBRT
      will receive a dose and fractionation schedule dependent on OPD lesion site and proximity to
      critical normal tissues. All patients will be seen 8 weeks post randomisation, then 3 monthly
      in line with routine care.

      HALT aims to assess whether in patients with mutation positive advanced NSCLC the use of SBRT
      to ≤ 3 sites of OPD with continuation of TKI improves progression-free survival (PFS)
      compared with continuation of TKI alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: Time from randomisation to the first of one of the above events or death. Assessed 8 weeks post-randomisation and 3-monthly thereafter (up to 24 months)
description: The primary outcome measure is progression free survival defined as the time from randomisation to the first of one of the following events or death from any cause:
Clinically symptomatic progression requiring palliative tumour-specific oncological intervention (e.g. change in systemic therapy or localised non-SBRT radiotherapy) as determined by the treating physician.
New or existing intra-cranial lesions not amenable to radical surgery or Stereotactic radiosurgery (SRS).
Development of new extra-cranial lesions or progression of existing extra-cranial lesions not meeting the criteria for
SBRT treatment (e.g. size >5cm)
Development of >3 new or progressing extra-cranial lesion at any one point in time (i.e. widespread progression)
measure: Time to next line of systemic therapy or palliative care
time frame: Time from randomisation to change in therapy or referral to palliative care due to clinical progression as determined by the treating physician, or death. Assessed 3-monthly until progression and 6-monthly thereafter (up to 24 months).
measure: Overall survival
time frame: Time from randomisation until death from any cause. Assessed up to 24 months.
measure: Patterns of disease progression identified from CT scans to further document natural history of oncogene-addicted NSCLC
time frame: Assessed 3-monthly up to 24 months.
measure: Radiotherapy toxicities (acute events)
time frame: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
description: Acute events are defined as ≤ 90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant) assessed using CTCAE v4.0.
measure: Radiotherapy toxicities (late events)
time frame: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
description: Late events are defined as > 90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant) assessed using RTOG.
measure: Quality of Life (EQ-5D-5L)
time frame: Baseline, 8 weeks and at the first 3 month visit.
description: Assessed using EQ-5D-5L
measure: Quality of Life (EORTC QLQ-C30)
time frame: Baseline, 8 weeks and at the first 3 month visit.
description: Assessed using EORTC QLQ-C30
measure: Measurement of resistant sub-clones in Circulating tumour DNA (ctDNA)
time frame: Baseline, 8 weeks post-randomisation and 3-monthly intervals during follow-up (up to 24 months).
measure: Time to failure of next line treatment
time frame: Time from randomisation to disease progression on next line of active systemic therapy. Assessed up to 24 months.
arm group label: SBRT and continued TKI therapy
arm group type: Experimental
description: Patients will continue to receive background TKI treatment as prior to trial entry.
Simultaneous administration (SBRT & TKI) or break in TKI during SBRT will be by centre preference and determined prior to commencing recruitment.
Repeat SBRT will be permissible upon development of subsequent OPD lesions dependent on SBRT suitability and total progression lesion number at any one point remaining ≤ 3.
arm group label: Continued TKI therapy alone
arm group type: Active Comparator
description: Continuation on the same background TKI treatment as prior to trial entry
intervention type: Radiation
intervention name: SBRT
description: SBRT dose and fractionation dependent on site of metastasis and proximity to critical normal tissues.
arm group label: SBRT and continued TKI therapy
other name: Stereotactic body radiotherapy
other name: SABR
intervention type: Drug
intervention name: TKI
description: Continued background TKI alone
arm group label: Continued TKI therapy alone
other name: Tyrosine Kinase Inhibitor
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Fiona McDonald, MD
role: Principal Investigator
affiliation: Royal Marsden NHS Foundation Trust
last name: HALT Trial Manager
phone: +442087224554
email: halt-icrctsu@icr.ac.uk
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Tyrosine Protein Kinase Inhibitors