<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/NCT03769103</url>
  </required_header>
  <id_info>
    <org_study_id>LUOSICNS</org_study_id>
    <nct_id>NCT03769103</nct_id>
  </id_info>
  <brief_title>Study of Osimertinib + SRS vs Osimertinib Alone for Brain Metastases in EGFR Positive Patients With NSCLC</brief_title>
  <official_title>Open Label, Multicenter, Phase II Study of Patients With Treatment Naïve Metastatic Epidermal Growth Factor Receptor (EGFR) Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases Randomized to Stereotactic Radiosurgery (SRS) and Osimertinib or Osimertinib Alone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>British Columbia Cancer Agency</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Princess Margaret Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>British Columbia Cancer Agency</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>
      This open-label, multicenter, randomized phase II study will evaluate the usage of&#xD;
      osimertinib alone for brain metastases compared to SRS and osimertinib in patients with newly&#xD;
      diagnosed, treatment naiive EGFR positive lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 19, 2019</start_date>
  <completion_date type="Anticipated">April 2025</completion_date>
  <primary_completion_date type="Anticipated">April 2025</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>Intracranial progression free survival</measure>
    <time_frame>1 year</time_frame>
    <description>Absence of progressive brain metastases according to the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM criteria)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intracranial overall response rate</measure>
    <time_frame>2 years</time_frame>
    <description>partial or complete response to therapy based on RANO-BM criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to whole brain radiotherapy (WBRT)</measure>
    <time_frame>2 years</time_frame>
    <description>time from randomization to WBRT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to stereotactic radiosurgery (SRS)</measure>
    <time_frame>2 years</time_frame>
    <description>time from randomization to SRS (not including initial SRS in the SRS + osimertinib treatment arm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of radionecrosis</measure>
    <time_frame>2 years</time_frame>
    <description>according to institutional standards based on radiologic findings with or without pathologic confirmation and multidisciplinary review when required</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
    <description>defined as time from randomization to death by any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to distant progression</measure>
    <time_frame>2 years</time_frame>
    <description>time from randomization to progression of extracranial metastases or development of new sites of disease per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. Subscales for: general presence of symptoms in patients with cancer question 1-28 (1=Not at all; 4=very much); overall health/quality of life question 29-30 (1=very poor; 7=excellent) &amp; EORTC-QLQ Brain Neoplasm (BN)20: Subscales for presence of symptoms in patients with brain tumours question 31-50 (1=Not at all; 4=very much)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurocognitive function</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed by Montreal Cognitive Assessment. Total score:30. 1=poor function; 30=good function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exposure to osimertinib</measure>
    <time_frame>2 years</time_frame>
    <description>Osimertinib dose (40mg or 80mg) for x number of days (max=730 days)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">76</enrollment>
  <condition>Lung Cancer Non-small Cell Stage IV</condition>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>SRS + Osimertinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Stereotactic radiotherapy will be delivered in 1-5 fractions to each brain metastases according to the volume and location of the metastases and clinician discretion. Osimertinib will start 1-7 days post radiotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Osimertinib alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Osimertinib 80mg PO daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Osimertinib</intervention_name>
    <description>Daily oral osimertinib</description>
    <arm_group_label>Osimertinib alone</arm_group_label>
    <arm_group_label>SRS + Osimertinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic radiotherapy</intervention_name>
    <description>1-5 fractions of stereotactic radiotherapy</description>
    <arm_group_label>SRS + Osimertinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to provide written informed consent by patient or legally acceptable&#xD;
             representative&#xD;
&#xD;
          -  Meets the criteria in the approved regulatory indication for first line treatment with&#xD;
             osimertinib and agree to the restrictions, monitoring, and dose-adjustment criteria&#xD;
             stipulated in the associated product label&#xD;
&#xD;
          -  Epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R)&#xD;
             substitution mutations (either alone or in combination with other EGFR mutations)&#xD;
&#xD;
          -  No prior systemic therapy except neoadjuvant, adjuvant or concurrent chemotherapy&#xD;
             given greater than 3 months prior to enrollment on study&#xD;
&#xD;
          -  Asymptomatic or minimally symptomatic brain metastases (ie. Headache, nausea, or&#xD;
             seizure responsive to dexamethasone/analgesic/antiepileptic on stable doses of&#xD;
             medications for a minimum of 3 days)&#xD;
&#xD;
          -  Brain metastases must meet the following criteria on a diagnostic MRI: at least one&#xD;
             lesion can be classified as measurable disease per RANO-BM, ≤ 10 brain or brainstem&#xD;
             metastases, ≤ 30 mm and brainstem metastases must be ≤ 5 mm, metastases &gt; 5 mm from&#xD;
             the optic nerve or chiasm&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Life expectancy &gt; 6 months&#xD;
&#xD;
          -  Willing to abstain from sexual activity or willing to use double-barrier method during&#xD;
             sexual intercourse&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with osimertinib, or any other EGFR TKI&#xD;
&#xD;
          -  Patient with symptomatic brain metastases causing any neurologic deficit (not&#xD;
             including headache, nausea, or medically controlled seizure)&#xD;
&#xD;
          -  Multiple sclerosis&#xD;
&#xD;
          -  Pacemaker or MRI-incompatible metal in the body&#xD;
&#xD;
          -  Allergy to gadolinium MRI contrast&#xD;
&#xD;
          -  Brain metastasis requiring surgery for decompression&#xD;
&#xD;
          -  Leptomeningeal disease&#xD;
&#xD;
          -  Previous cranial RT, or surgery for brain metastases&#xD;
&#xD;
          -  Uncontrolled systemic lupus erythematosis, scleroderma or other connective tissue&#xD;
             disorders considered a contraindication for radiotherapy&#xD;
&#xD;
          -  Active cancer from another anatomical site within 5 years (non-melanomatous skin and&#xD;
             cervical cancers permitted)&#xD;
&#xD;
          -  Any medical or non-medical issue that would render patient unable to reliably complete&#xD;
             regular QOL and neurocognitive assessments&#xD;
&#xD;
          -  Judgment by the investigator that the patient should not participate in the study if&#xD;
             the patient is unlikely to comply with study procedures, restrictions and requirements&#xD;
&#xD;
          -  Treatment with an investigational drug within five half-lives of the compound or 3&#xD;
             months, whichever is greater&#xD;
&#xD;
          -  Patients with symptomatic CNS metastases who are neurologically unstable&#xD;
&#xD;
          -  Patients currently receiving (or unable to stop use prior to receiving the first dose&#xD;
             of study treatment) medications or herbal supplements known to be potent inducers of&#xD;
             cytochrome P450 (CYP) 3A4&#xD;
&#xD;
          -  Patients taking any drugs that are known to prolong QT interval that can't be&#xD;
             withdrawn prior to Osimertinib&#xD;
&#xD;
          -  Pregnant or breastfeeding&#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>Shilo V Lefresne, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>BC Cancer, Vancouver Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cheryl Ho, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>BC Cancer, Vancouver Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shilo V Lefresne, MD, FRCPC</last_name>
    <phone>604 877 6000</phone>
    <phone_ext>2673</phone_ext>
    <email>SLefresne@bccancer.bc.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Cheryl Ho, MD, FRCPC</last_name>
    <phone>604 877 6000</phone>
    <email>cho@bccancer.bc.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>BC Cancer, Vancouver Centre</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shilo Lefresne, MD</last_name>
      <phone>604 877 6000</phone>
      <phone_ext>2673</phone_ext>
      <email>slefresne@bccancer.bc.ca</email>
    </contact>
    <contact_backup>
      <last_name>Cheryl Ho, MD</last_name>
      <phone>604 877 6000</phone>
      <phone_ext>2445</phone_ext>
      <email>cho@bccancer.bc.ca</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adrian Sacher</last_name>
    </contact>
    <contact_backup>
      <last_name>David Shultz</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark Doherty</last_name>
    </contact>
    <contact_backup>
      <last_name>Arjun Sahgal</last_name>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>February 1, 2021</last_update_submitted>
  <last_update_submitted_qc>February 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EGFR positive</keyword>
  <keyword>Osimertinib</keyword>
  <keyword>SRS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osimertinib</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/NCT03769103
org study id: LUOSICNS
nct id: NCT03769103
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This open-label, multicenter, randomized phase II study will evaluate the usage of
      osimertinib alone for brain metastases compared to SRS and osimertinib in patients with newly
      diagnosed, treatment naiive EGFR positive lung cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Intracranial progression free survival
time frame: 1 year
description: Absence of progressive brain metastases according to the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM criteria)
measure: Intracranial overall response rate
time frame: 2 years
description: partial or complete response to therapy based on RANO-BM criteria
measure: Time to whole brain radiotherapy (WBRT)
time frame: 2 years
description: time from randomization to WBRT
measure: Time to stereotactic radiosurgery (SRS)
time frame: 2 years
description: time from randomization to SRS (not including initial SRS in the SRS + osimertinib treatment arm)
measure: Rate of radionecrosis
time frame: 2 years
description: according to institutional standards based on radiologic findings with or without pathologic confirmation and multidisciplinary review when required
measure: Overall survival
time frame: 2 years
description: defined as time from randomization to death by any cause
measure: Time to distant progression
time frame: 2 years
description: time from randomization to progression of extracranial metastases or development of new sites of disease per RECIST 1.1
measure: Quality of life
time frame: 2 years
description: Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. Subscales for: general presence of symptoms in patients with cancer question 1-28 (1=Not at all; 4=very much); overall health/quality of life question 29-30 (1=very poor; 7=excellent) & EORTC-QLQ Brain Neoplasm (BN)20: Subscales for presence of symptoms in patients with brain tumours question 31-50 (1=Not at all; 4=very much)
measure: Neurocognitive function
time frame: 2 years
description: Assessed by Montreal Cognitive Assessment. Total score:30. 1=poor function; 30=good function
measure: Exposure to osimertinib
time frame: 2 years
description: Osimertinib dose (40mg or 80mg) for x number of days (max=730 days)
arm group label: SRS + Osimertinib
arm group type: Active Comparator
description: Stereotactic radiotherapy will be delivered in 1-5 fractions to each brain metastases according to the volume and location of the metastases and clinician discretion. Osimertinib will start 1-7 days post radiotherapy.
arm group label: Osimertinib alone
arm group type: Experimental
description: Osimertinib 80mg PO daily
intervention type: Drug
intervention name: Osimertinib
description: Daily oral osimertinib
arm group label: Osimertinib alone
arm group label: SRS + Osimertinib
intervention type: Radiation
intervention name: Stereotactic radiotherapy
description: 1-5 fractions of stereotactic radiotherapy
arm group label: SRS + Osimertinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shilo V Lefresne, MD, FRCPC
role: Principal Investigator
affiliation: BC Cancer, Vancouver Centre
last name: Cheryl Ho, MD, FRCPC
role: Principal Investigator
affiliation: BC Cancer, Vancouver Centre
last name: Shilo V Lefresne, MD, FRCPC
phone: 604 877 6000
phone ext: 2673
email: SLefresne@bccancer.bc.ca
last name: Cheryl Ho, MD, FRCPC
phone: 604 877 6000
email: cho@bccancer.bc.ca
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Osimertinib
sharing ipd: Undecided