xml: <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/NCT05987644</url>
    </required_header>
    <id_info>
      <org_study_id>HCRN-LUN21-534</org_study_id>
      <nct_id>NCT05987644</nct_id>
    </id_info>
    <brief_title>Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and ALK rEarrangements</brief_title>
    <acronym>DURABLE</acronym>
    <official_title>DURABLE: Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and rEarrangements</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Joshua Palmer</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Genentech, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Hoosier Cancer Research Network</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will consist of a Phase 1b and Phase 2 portion and both will enroll&#xD;
        simultaneously. Subjects with &gt; 15 CNS metastases will be enrolled in the Phase 1b portion of&#xD;
        the study. Subjects with 1-15 CNS metastases will be enrolled in the Phase 2 portion of the&#xD;
        study.&#xD;
  &#xD;
        Subjects will receive alectinib twice daily. Those in the Phase 1b portion will receive&#xD;
        alectinib alone. Those in Phase 2 Arm A will receive alectinib alone. Those in Phase 2, Arm B&#xD;
        will receive SRS + alectinib.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">February 2025</completion_date>
    <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
    <phase>Phase 1/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>Phase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases</measure>
      <time_frame>12 months</time_frame>
      <description>Neurological status will be measured by a composite endpoint of:&#xD;
  -Inntracranial progression(icPD) by RANO-BM criteria or death during the first 12 months.&#xD;
  OR&#xD;
  -Symptomatic radiation necrosis during the first 12 months. Symptomatic radiation necrosis is defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery.&#xD;
  OR&#xD;
  -Cognitive decline, defined as 1 standard deviation decline from baseline cognitive function during the first 12 months.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1b: Safety and Feasibility</measure>
      <time_frame>6 months</time_frame>
      <description>Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Intracranial progression-free survival at 12 months (icPFS12)</measure>
      <time_frame>12 months</time_frame>
      <description>icPFS12 is the percentage of patients with icPD at 12 months defined by RANO-BM from randomization or death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial disease control rate (icDCR)</measure>
      <time_frame>31 months</time_frame>
      <description>icDCR defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), per RANO-BM.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial response rate (icRR)</measure>
      <time_frame>31 months</time_frame>
      <description>icRR defined as the percentage of patients with a complete response (CR) and partial response (PR), per RANO-BM.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial duration of response (icDOR)</measure>
      <time_frame>31 months</time_frame>
      <description>icDOR defined as the time when the criteria for CR or PR per RANO-BM were first met to the occurrence of an icPFS event</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Extracranial PFS</measure>
      <time_frame>31 months</time_frame>
      <description>Extracranial PFS will be defined as time from randomization to progression per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assess Overall survival (OS)</measure>
      <time_frame>31 months</time_frame>
      <description>OS defined as the time from randomization to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety and Tolerability</measure>
      <time_frame>6 months</time_frame>
      <description>Safety and tolerability will be assessed by measuring the frequency and severity of adverse events based on CTCAE v5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cognitive decline at 12 and 24 months</measure>
      <time_frame>12, 24 months</time_frame>
      <description>Rate of cognitive decline, defined as 1 standard deviation decline from baseline cognitive function in at least 1 cognitive test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Symptomatic radiation necrosis at 12 and 24 months</measure>
      <time_frame>12, 24 months</time_frame>
      <description>Incidence of symptomatic radiation necrosis, defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">56</enrollment>
    <condition>Lung Cancer</condition>
    <condition>NSCLC</condition>
    <condition>Brain Metastases</condition>
    <arm_group>
      <arm_group_label>Phase 1b: Experimental</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>600mg alectinib taken orally twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 2: Arm A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>600mg alectinib taken orally twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 2: Arm B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will receive SRS prior to taking alectinib. 24 hours after, but no more than 7 days after last radiation dose, alectinib should be taken at 600mg orally twice daily</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Alectinib</intervention_name>
      <description>600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)</description>
      <arm_group_label>Phase 1b: Experimental</arm_group_label>
      <arm_group_label>Phase 2: Arm A</arm_group_label>
      <arm_group_label>Phase 2: Arm B</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Stereotactic Radiosurgery</intervention_name>
      <description>SRS dose varies by brain met size and location</description>
      <arm_group_label>Phase 2: Arm B</arm_group_label>
      <other_name>SRS</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria for Phase 2:&#xD;
  &#xD;
          1. Subjects must have 1-15 intracranial metastases less than 3 cm with only 1 lesion more&#xD;
          than 2 cm.&#xD;
  &#xD;
          Inclusion Criteria for Phase 1b:&#xD;
  &#xD;
          1. Subjects must have &gt; 15 intracranial metastases all less than 3 cm in maximum dimension.&#xD;
  &#xD;
          General Inclusion Criteria:&#xD;
  &#xD;
          Subject must meet all of the following applicable inclusion criteria to participate in this&#xD;
          study:&#xD;
  &#xD;
            1. Written informed consent and HIPAA authorization for release of personal health&#xD;
               information prior to registration. NOTE: HIPAA authorization may be included in the&#xD;
               informed consent or obtained separately.&#xD;
  &#xD;
            2. Age ≥ 18 years at the time of consent.&#xD;
  &#xD;
            3. First language must be English.&#xD;
  &#xD;
            4. ECOG Performance Status of ≤ 2 within 14 days prior to registration.&#xD;
  &#xD;
            5. Histological or cytological confirmation of Stage IV (per AJCC 8th edition) non-small&#xD;
               cell lung cancer (NSCLC).&#xD;
  &#xD;
            6. Confirmation of positive ALK rearrangement per local testing per standard of care.&#xD;
  &#xD;
            7. All subjects must have brain metastases and be either asymptomatic or minimally&#xD;
               symptomatic per investigator discretion without plan for surgical intervention within&#xD;
               28 days of study start. Patients with neurological symptoms that are controlled with&#xD;
               dose of corticosteroids or anti-epileptic medications are eligible. The protocol&#xD;
               defines Phase 1b and Phase 2 eligibility based on number of brain metastases.&#xD;
  &#xD;
            8. Documentation of consultation with a radiation oncologist confirming agreement to&#xD;
               delay radiation therapy.&#xD;
  &#xD;
            9. Demonstrate adequate organ function as defined in the protocol. All screening labs to&#xD;
               be obtained within 14 days prior to registration.&#xD;
  &#xD;
           10. Females of childbearing potential must have a negative serum pregnancy test within 14&#xD;
               days prior to registration. See protocol for definition of childbearing potential.&#xD;
  &#xD;
           11. Females of childbearing potential and males must be willing to abstain from&#xD;
               heterosexual intercourse or to use an effective method(s) of contraception as outlined&#xD;
               in the protocol.&#xD;
  &#xD;
           12. HIV-infected patients on effective anti-retroviral therapy with undetectable viral&#xD;
               load within 6 months of registration are eligible for this trial.&#xD;
  &#xD;
           13. Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral&#xD;
               load must be undetectable on suppressive therapy, if indicated. Patients with a&#xD;
               history of hepatitis C virus (HCV) infection must have been treated and cured. For&#xD;
               patients with HCV infection who are currently on treatment, the HCV viral load must be&#xD;
               undetectable to be eligible for this trial.&#xD;
  &#xD;
           14. As determined by the enrolling physician or protocol designee, ability of the subject&#xD;
               to understand and comply with study procedures for the entire length of the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Subjects meeting any of the criteria below may not participate in the study:&#xD;
  &#xD;
            1. No prior treatment with alectinib.&#xD;
  &#xD;
            2. No prior systemic therapy for metastatic disease is permitted. Patients who have&#xD;
               received prior neoadjuvant, adjuvant chemotherapy, radiotherapy, immunotherapy (PD-1&#xD;
               or PD-L1 monoclonal antibodies) or chemoradiotherapy with curative intent for&#xD;
               non-metastatic disease must have experienced a treatment-free interval of at least 3&#xD;
               months from enrollment since the last chemotherapy, radiotherapy, immunotherapy, or&#xD;
               chemoradiotherapy cycle.&#xD;
  &#xD;
            3. Active infection requiring systemic therapy.&#xD;
  &#xD;
            4. Malabsorption syndrome or other condition that would interfere with enteral absorption&#xD;
  &#xD;
            5. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the&#xD;
               mother is being treated on study).&#xD;
  &#xD;
            6. Patients with a prior or concurrent malignancy whose natural history or treatment has&#xD;
               the potential to interfere with the safety or efficacy assessment of the&#xD;
               investigational regimen, per treating physician discretion, are not eligible for this&#xD;
               trial.&#xD;
  &#xD;
            7. Treatment with any investigational drug within 28 days prior to registration.&#xD;
  &#xD;
            8. History of other malignancy within 5 years prior to screening, except for&#xD;
               appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or&#xD;
               Stage I uterine cancer.&#xD;
  &#xD;
            9. Acute viral, autoimmune, alcoholic, or other types of acute hepatitis.&#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>Joshua D Palmer, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Joshua D Palmer, MD</last_name>
      <phone>614-293-0871</phone>
      <email>joshua.palmer@osumc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Kimberly Cameron</last_name>
      <phone>317-634-5842</phone>
      <phone_ext>39</phone_ext>
      <email>kcameron@hoosiercancer.org</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Hoosier Cancer Research Network</investigator_affiliation>
      <investigator_full_name>Joshua Palmer</investigator_full_name>
      <investigator_title>Sponsor-Investigator</investigator_title>
    </responsible_party>
    <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>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05987644
  org study id: HCRN-LUN21-534
  nct id: NCT05987644
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This study will consist of a Phase 1b and Phase 2 portion and both will enroll
        simultaneously. Subjects with > 15 CNS metastases will be enrolled in the Phase 1b portion of
        the study. Subjects with 1-15 CNS metastases will be enrolled in the Phase 2 portion of the
        study.
  
        Subjects will receive alectinib twice daily. Those in the Phase 1b portion will receive
        alectinib alone. Those in Phase 2 Arm A will receive alectinib alone. Those in Phase 2, Arm B
        will receive SRS + alectinib.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Phase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases
  time frame: 12 months
  description: Neurological status will be measured by a composite endpoint of:
  -Inntracranial progression(icPD) by RANO-BM criteria or death during the first 12 months.
  OR
  -Symptomatic radiation necrosis during the first 12 months. Symptomatic radiation necrosis is defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery.
  OR
  -Cognitive decline, defined as 1 standard deviation decline from baseline cognitive function during the first 12 months.
  measure: Phase 1b: Safety and Feasibility
  time frame: 6 months
  description: Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities.
  measure: Intracranial progression-free survival at 12 months (icPFS12)
  time frame: 12 months
  description: icPFS12 is the percentage of patients with icPD at 12 months defined by RANO-BM from randomization or death.
  measure: Intracranial disease control rate (icDCR)
  time frame: 31 months
  description: icDCR defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), per RANO-BM.
  measure: Intracranial response rate (icRR)
  time frame: 31 months
  description: icRR defined as the percentage of patients with a complete response (CR) and partial response (PR), per RANO-BM.
  measure: Intracranial duration of response (icDOR)
  time frame: 31 months
  description: icDOR defined as the time when the criteria for CR or PR per RANO-BM were first met to the occurrence of an icPFS event
  measure: Extracranial PFS
  time frame: 31 months
  description: Extracranial PFS will be defined as time from randomization to progression per RECIST v1.1
  measure: Assess Overall survival (OS)
  time frame: 31 months
  description: OS defined as the time from randomization to death from any cause.
  measure: Safety and Tolerability
  time frame: 6 months
  description: Safety and tolerability will be assessed by measuring the frequency and severity of adverse events based on CTCAE v5.0
  measure: Cognitive decline at 12 and 24 months
  time frame: 12, 24 months
  description: Rate of cognitive decline, defined as 1 standard deviation decline from baseline cognitive function in at least 1 cognitive test.
  measure: Symptomatic radiation necrosis at 12 and 24 months
  time frame: 12, 24 months
  description: Incidence of symptomatic radiation necrosis, defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery.
  arm group label: Phase 1b: Experimental
  arm group type: Experimental
  description: 600mg alectinib taken orally twice daily
  arm group label: Phase 2: Arm A
  arm group type: Experimental
  description: 600mg alectinib taken orally twice daily
  arm group label: Phase 2: Arm B
  arm group type: Experimental
  description: Subjects will receive SRS prior to taking alectinib. 24 hours after, but no more than 7 days after last radiation dose, alectinib should be taken at 600mg orally twice daily
  intervention type: Drug
  intervention name: Alectinib
  description: 600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)
  arm group label: Phase 1b: Experimental
  arm group label: Phase 2: Arm A
  arm group label: Phase 2: Arm B
  intervention type: Radiation
  intervention name: Stereotactic Radiosurgery
  description: SRS dose varies by brain met size and location
  arm group label: Phase 2: Arm B
  other name: SRS
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Joshua D Palmer, MD
  role: Principal Investigator
  affiliation: The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  last name: Joshua D Palmer, MD
  phone: 614-293-0871
  email: joshua.palmer@osumc.edu
  last name: Kimberly Cameron
  phone: 317-634-5842
  phone ext: 39
  email: kcameron@hoosiercancer.org
  responsible party type: Sponsor-Investigator
  investigator affiliation: Hoosier Cancer Research Network
  investigator full name: Joshua Palmer
  investigator title: Sponsor-Investigator
  mesh term: Lung Neoplasms
  mesh term: Neoplasm Metastasis
  mesh term: Brain Neoplasms