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/NCT06014827</url>
    </required_header>
    <id_info>
      <org_study_id>22624</org_study_id>
      <secondary_id>NCI-2023-06041</secondary_id>
      <secondary_id>22624</secondary_id>
      <secondary_id>P30CA033572</secondary_id>
      <nct_id>NCT06014827</nct_id>
    </id_info>
    <brief_title>Biologically Guided Radiation Therapy (BgRT) and Stereotactic Body Radiation Therapy (SBRT) With Osimertinib for the Treatment of Patients With Oligoprogressive EGFR Positive Non-small Cell Lung Carcinoma</brief_title>
    <official_title>Phase II Trial of the Addition of Biologically Guided Radiation Therapy (BgRT) and Stereotactic Body Radiation Therapy (SBRT) to First Line Osimertinib in Oligoprogressive EGFR Positive Non-Small Cell Lung Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>City of Hope Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>City of Hope Medical Center</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase II trial tests how well biologically guided radiation therapy (BgRT) and&#xD;
        stereotactic body radiation therapy (SBRT) with osimertinib works for the treatment of EGFR&#xD;
        positive non-small cell lung carcinoma that has spread from where it first started (primary&#xD;
        site) to a limited number of anatomic sites (oligoprogressive). BgRT is radiation that uses&#xD;
        specialized imaging to during treatment to target the active tumor and direct radiation to&#xD;
        tumors in order to kill and shrink tumor cells. Stereotactic body radiation therapy uses&#xD;
        special equipment to position a patient and deliver radiation to tumors with high precision.&#xD;
        This method may kill tumor cells with fewer doses over a shorter period and cause less damage&#xD;
        to normal tissue. Osimertinib is in a class of medications called kinase inhibitors. It works&#xD;
        by blocking the action of a protein called EGFR that signals cancer cells to multiply. This&#xD;
        helps slow or stop the spread of tumor cells. Giving BgRT with SBRT and osimertinib may kill&#xD;
        more tumor cells in patients with oligoprogressive EGFR positive non-small cell lung&#xD;
        carcinoma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. To estimate the percent of patients receiving benefit at 6 months from the addition of&#xD;
        BgRT/SBRT to first line osimertinib in EGFR positive non-small cell lung cancer (NSCLC)&#xD;
        patients with oligoprogressive disease (disease control rate [DCR]).&#xD;
  &#xD;
        SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. To evaluate the tolerability of adding BgRT/SBRT to first line osimertinib in EGFR&#xD;
        positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        II. To estimate the overall survival when adding BgRT/SBRT to first line osimertinib in EGFR&#xD;
        positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        III. To describe the effect on quality of life (QOL) when adding BgRT/SBRT to first line&#xD;
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        IV. To describe the effect on quantified fludeoxyglucose F-18 (FDG) uptake changes when&#xD;
        adding BgRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive&#xD;
        disease.&#xD;
  &#xD;
        V. To estimate local and distant control rates when adding BgRT/SBRT to first line&#xD;
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        VI. To estimate the extracranial progression free survival (PFS) when adding SBRT to first&#xD;
        line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        VII. To estimate the time to treatment failure (TTF) when adding BgRT/SBRT to first line&#xD;
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        VII. To estimate percentage of patients needing salvage BgRT/SBRT when adding SBRT to first&#xD;
        line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        EXPLORATORY OBJECTIVES:&#xD;
  &#xD;
        I. To identify potential predictors of outcome when adding BgRT/SBRT to first line&#xD;
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.&#xD;
  &#xD;
        II. To describe the changes in circulating tumor deoxyribonucleic acid (ctDNA) levels when&#xD;
        adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with&#xD;
        oligoprogressive disease.&#xD;
  &#xD;
        OUTLINE:&#xD;
  &#xD;
        Patients continue to receive osimertinib orally (PO) daily (QD) in the absence of&#xD;
        unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients&#xD;
        then continue to receive osimertinib and are monitored via imaging. If additional progression&#xD;
        is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the&#xD;
        absence of &gt; 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib&#xD;
        for more than 4 weeks.&#xD;
  &#xD;
        Patients undergo computed tomography (CT) scan or positron emission tomography(PET)/CT scan&#xD;
        and blood sample collection throughout the study.&#xD;
  &#xD;
        After completion of initial radiation therapy, patients follow up at 1 week, 3 months, 6&#xD;
        months and 12 months and then for an additional year.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 25, 2023</start_date>
    <completion_date type="Anticipated">May 9, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 9, 2025</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>Percent of patients on planned protocol treatment</measure>
      <time_frame>At 6 months</time_frame>
      <description>Patient counts and percentages will be provided.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Rate of all grades and grade &gt;= 3 adverse events at least possibly related to study therapy</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>As measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Observed toxicities will be summarized, for all patients in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>From the date of study enrollment to the date of death from any cause, up to 2 years</time_frame>
      <description>Will be estimated using the product-limit method of Kaplan-Meier. Two-sided 95% confidence intervals will be computed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in quality of life (QOL)</measure>
      <time_frame>From baseline to 3 months post initial stereotactic body radiation therapy (SBRT)</time_frame>
      <description>As measured by Functional Assessment of Cancer Therapy-General (FACT-G) v4. Repeated QOL assessments will be tabulated and graphically displayed to describe the changes of QOL outcomes over time.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in fludeoxyglucose (FDG) uptake</measure>
      <time_frame>From baseline to completion of SBRT, up to 2 years</time_frame>
      <description>As measured by metabolic tumor volume and total lesion glycolysis at each fraction. Will be analyzed using independent student's t-test to compare normal variables and non-parametric tests including Wilcoxon's signed-rank test for paired data will be used to compare non-normally distributed variables. Repeated measures analysis of variance (ANOVA) will be used to test for differences at more than one time point. Correlation between metabolic tumor volume, total lesion glycolysis and circulating tumor deoxyribonucleic acid (ctDNA) and time to treatment failure (as described above) as well as overall survival will be explored using univariate and multivariate Cox regression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ratio of patients achieving local control and distant control</measure>
      <time_frame>Up to 2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>First occurrence of disease progression</measure>
      <time_frame>From study entry to first occurrence of disease progression, up to 2 years</time_frame>
      <description>By Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) v1.0 or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A progressive event will occur when: more than five sites of progression based on PERCIST or RECIST, inability to receive more biologically guided radiation therapy (BgRT)/SBRT or osimertinib, physician decision to come off study or change therapy, patient withdrawal of consent or death will all be considered events. Will be estimated using the product-limit method of Kaplan-Meier.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to treatment failure</measure>
      <time_frame>From study entry to treatment failure, up to 2 years</time_frame>
      <description>Will be estimated using the product-limit method of Kaplan-Meier. For time to treatment failure, a progressive event will occur when: more than five sites of progression based on PERCIST or RECIST, inability to receive more BgRT/SBRT or osimertinib, physician decision to come off study or change therapy, patient withdrawal of consent or death will all be considered events.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ratio of patients needing salvage BgRT/SBRT</measure>
      <time_frame>Up to 1 year</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">32</enrollment>
    <condition>Lung Non-Small Cell Carcinoma</condition>
    <condition>Stage IV Lung Cancer AJCC v8</condition>
    <arm_group>
      <arm_group_label>Treatment (BgRT/SBRT)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients continue to receive osimertinib PO QD in the absence of unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients then continue to receive osimertinib and are monitored via imaging. If additional progression is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the absence of &gt; 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib for more than 4 weeks.&#xD;
  Patients undergo CT scan or PET/CT scan and blood sample collection throughout the study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Treatment (BgRT/SBRT)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo CT or PET/CT scan</description>
      <arm_group_label>Treatment (BgRT/SBRT)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Osimertinib</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Treatment (BgRT/SBRT)</arm_group_label>
      <other_name>AZD-9291</other_name>
      <other_name>AZD9291</other_name>
      <other_name>Mereletinib</other_name>
      <other_name>Tagrisso</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Positron Emission Tomography</intervention_name>
      <description>Undergo PET/CT</description>
      <arm_group_label>Treatment (BgRT/SBRT)</arm_group_label>
      <other_name>Medical Imaging, Positron Emission Tomography</other_name>
      <other_name>PET</other_name>
      <other_name>PET Scan</other_name>
      <other_name>Positron emission tomography (procedure)</other_name>
      <other_name>Positron Emission Tomography Scan</other_name>
      <other_name>Positron-Emission Tomography</other_name>
      <other_name>proton magnetic resonance spectroscopic imaging</other_name>
      <other_name>PT</other_name>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Stereotactic Body Radiation Therapy</intervention_name>
      <description>Undergo BgRT/SBRT</description>
      <arm_group_label>Treatment (BgRT/SBRT)</arm_group_label>
      <other_name>SABR</other_name>
      <other_name>SBRT</other_name>
      <other_name>Stereotactic Ablative Body Radiation Therapy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Survey Administration</intervention_name>
      <description>Ancillary study</description>
      <arm_group_label>Treatment (BgRT/SBRT)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Documented informed consent of the participant and/or legally authorized&#xD;
               representative&#xD;
  &#xD;
                 -  Assent, when appropriate, will be obtained per institutional guidelines&#xD;
  &#xD;
            -  Age: &gt;= 18 years&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) =&lt; 2&#xD;
  &#xD;
            -  Histologically confirmed advanced non-small cell lung cancer (NSCLC)&#xD;
  &#xD;
            -  The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations&#xD;
               known to be associated with epidermal growth factor receptor tyrosine kinase&#xD;
               inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination&#xD;
               with other epidermal growth factor receptor (EGFR) mutations, which may include T790M.&#xD;
  &#xD;
            -  Disease progression in the metastatic setting on PET or CT imaging when receiving&#xD;
               first line standard/approved single agent osimertinib after having had stable disease&#xD;
               (per Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1 or PET&#xD;
               Response Criteria in Solid Tumors [PERCIST] v 1.0) for more than 6 months&#xD;
  &#xD;
            -  Disease progression must be in the form of 1-5 extracranial sites (any number of&#xD;
               metastatic sites at initial diagnosis will qualify). For progression of the primary&#xD;
               and oligoprogressive site(s), the primary should be treated with curative/local&#xD;
               control intent. The primary, if progressing is considered as 1 site. Maximum of 3&#xD;
               lesions per organ (i.e. patient with 4 oligoprogressive sites in the lung would be&#xD;
               excluded). Each lesion will be considered as 1 &quot;site&quot; so 3 lesions in the lung for&#xD;
               example will be considered 3 sites. Patients with prior metastases that have been&#xD;
               treated with ablative therapies before their current line of systemic therapy are&#xD;
               eligible. Patients with brain metastases can be included but brain metastases must be&#xD;
               treated (asymptomatic and have had no requirement for steroid medication for 1 week&#xD;
               prior to the first dose of study drug and have completed radiation 2 weeks prior to&#xD;
               the first dose of study drug) prior to enrollment (brain metastases [mets] will not be&#xD;
               counted as a site of progression)&#xD;
  &#xD;
            -  Lesion(s) must be amenable to SBRT as determined by the radiation oncologist. If a&#xD;
               patient is unable to receive a minimum of 30 Gy in 5 fractions they will not qualify&#xD;
  &#xD;
            -  At least one lesion must be amenable to BgRT which includes either a lung or bone&#xD;
               metastasis, greater than or equal to 2 cm, which can also receive a minimum of 30 Gy&#xD;
               in 5 fractions&#xD;
  &#xD;
            -  No prior systemic therapy for advanced disease other than osimertinib&#xD;
  &#xD;
            -  Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the&#xD;
               urine test is positive or cannot be confirmed as negative, a serum pregnancy test will&#xD;
               be required&#xD;
  &#xD;
            -  Agreement by females and males of childbearing potential* to use an effective method&#xD;
               of birth control or abstain from heterosexual activity for the course of the study&#xD;
               through at least 4 months after the last dose of protocol therapy&#xD;
  &#xD;
                 -  Childbearing potential defined as not being surgically sterilized (men and women)&#xD;
                    or have not been free from menses for &gt; 1 year (women only)&#xD;
  &#xD;
            -  Patients must be able to swallow and retain oral medications&#xD;
  &#xD;
            -  Life expectancy of at least 6 months&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days&#xD;
               prior to day 1 of protocol therapy (6 weeks for nitrosoureas or mitomycin C).&#xD;
               Exceptions to this exclusion are brain radiation (2 weeks) and osimertinib&#xD;
  &#xD;
            -  Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy&#xD;
  &#xD;
            -  Patients receiving class 1A or class III antiarrhythmic agents within 14 days prior to&#xD;
               day 1 of protocol therapy&#xD;
  &#xD;
            -  Drugs known to prolong the corrected QT (QTc) interval&#xD;
  &#xD;
            -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
               composition to study agent&#xD;
  &#xD;
            -  Clinically significant uncontrolled illness&#xD;
  &#xD;
            -  Active infection requiring antibiotics bacterial, viral, or fungal infections,&#xD;
               requiring systemic therapy&#xD;
  &#xD;
            -  Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection&#xD;
  &#xD;
            -  Prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin&#xD;
               cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more&#xD;
               years prior to study entry with no subsequent evidence of recurrence. Patients with a&#xD;
               history of low grade (Gleason score =&lt; 6 =Gleason group 1) localized prostate cancer&#xD;
               will be eligible even if diagnosed less than 5 years prior to study entry. Other&#xD;
               malignancies with low probability of recurrence may be allowed with primary&#xD;
               investigator (PI) approval&#xD;
  &#xD;
            -  Females only: Pregnant or breastfeeding&#xD;
  &#xD;
            -  Any malabsorption condition&#xD;
  &#xD;
            -  Any other condition that would, in the Investigator's judgment, contraindicate the&#xD;
               patient's participation in the clinical study due to safety concerns with clinical&#xD;
               study procedures&#xD;
  &#xD;
            -  Diagnosis of congenital long QT syndrome&#xD;
  &#xD;
            -  New York Heart Association Class III or IV, cardiac disease, myocardial infarction&#xD;
               within the past 6 months, unstable arrhythmia, or evidence of ischemia on&#xD;
               electrocardiogram (ECG)&#xD;
  &#xD;
            -  Clinical evidence of central nervous system (CNS) metastases or leptomeningeal&#xD;
               carcinomatosis, except for individuals who have previously-treated CNS metastases, are&#xD;
               asymptomatic, and have had no requirement for steroid medication for 1 week prior to&#xD;
               the first dose of study drug and have completed radiation 2 weeks prior to the first&#xD;
               dose of study drug&#xD;
  &#xD;
            -  Patients with active interstitial lung disease (ILD) / pneumonitis or with a history&#xD;
               of ILD/ pneumonitis requiring steroids&#xD;
  &#xD;
            -  Prospective participants who, in the opinion of the investigator, may not be able to&#xD;
               comply with all study procedures (including compliance issues related to&#xD;
               feasibility/logistics)&#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>Arya Amini</last_name>
      <role>Principal Investigator</role>
      <affiliation>City of Hope Medical Center</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>City of Hope Medical Center</name>
        <address>
          <city>Duarte</city>
          <state>California</state>
          <zip>91010</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Arya Amini</last_name>
        <phone>626-218-2247</phone>
        <email>aamini@coh.org</email>
      </contact>
      <investigator>
        <last_name>Arya Amini</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Yale University</name>
        <address>
          <city>New Haven</city>
          <state>Connecticut</state>
          <zip>06520</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Henry S. Park</last_name>
        <email>henry.park@yale.edu</email>
      </contact>
      <investigator>
        <last_name>Henry S. Park</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</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>Carcinoma</mesh_term>
      <mesh_term>Lung 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>
    <!-- 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/NCT06014827
  org study id: 22624
  secondary id: NCI-2023-06041
  secondary id: 22624
  secondary id: P30CA033572
  nct id: NCT06014827
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase II trial tests how well biologically guided radiation therapy (BgRT) and
        stereotactic body radiation therapy (SBRT) with osimertinib works for the treatment of EGFR
        positive non-small cell lung carcinoma that has spread from where it first started (primary
        site) to a limited number of anatomic sites (oligoprogressive). BgRT is radiation that uses
        specialized imaging to during treatment to target the active tumor and direct radiation to
        tumors in order to kill and shrink tumor cells. Stereotactic body radiation therapy uses
        special equipment to position a patient and deliver radiation to tumors with high precision.
        This method may kill tumor cells with fewer doses over a shorter period and cause less damage
        to normal tissue. Osimertinib is in a class of medications called kinase inhibitors. It works
        by blocking the action of a protein called EGFR that signals cancer cells to multiply. This
        helps slow or stop the spread of tumor cells. Giving BgRT with SBRT and osimertinib may kill
        more tumor cells in patients with oligoprogressive EGFR positive non-small cell lung
        carcinoma.
  PRIMARY OBJECTIVE:
  
        I. To estimate the percent of patients receiving benefit at 6 months from the addition of
        BgRT/SBRT to first line osimertinib in EGFR positive non-small cell lung cancer (NSCLC)
        patients with oligoprogressive disease (disease control rate [DCR]).
  
        SECONDARY OBJECTIVES:
  
        I. To evaluate the tolerability of adding BgRT/SBRT to first line osimertinib in EGFR
        positive NSCLC patients with oligoprogressive disease.
  
        II. To estimate the overall survival when adding BgRT/SBRT to first line osimertinib in EGFR
        positive NSCLC patients with oligoprogressive disease.
  
        III. To describe the effect on quality of life (QOL) when adding BgRT/SBRT to first line
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.
  
        IV. To describe the effect on quantified fludeoxyglucose F-18 (FDG) uptake changes when
        adding BgRT to first line osimertinib in EGFR positive NSCLC patients with oligoprogressive
        disease.
  
        V. To estimate local and distant control rates when adding BgRT/SBRT to first line
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.
  
        VI. To estimate the extracranial progression free survival (PFS) when adding SBRT to first
        line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.
  
        VII. To estimate the time to treatment failure (TTF) when adding BgRT/SBRT to first line
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.
  
        VII. To estimate percentage of patients needing salvage BgRT/SBRT when adding SBRT to first
        line osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.
  
        EXPLORATORY OBJECTIVES:
  
        I. To identify potential predictors of outcome when adding BgRT/SBRT to first line
        osimertinib in EGFR positive NSCLC patients with oligoprogressive disease.
  
        II. To describe the changes in circulating tumor deoxyribonucleic acid (ctDNA) levels when
        adding BgRT/SBRT to first line osimertinib in EGFR positive NSCLC patients with
        oligoprogressive disease.
  
        OUTLINE:
  
        Patients continue to receive osimertinib orally (PO) daily (QD) in the absence of
        unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients
        then continue to receive osimertinib and are monitored via imaging. If additional progression
        is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the
        absence of > 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib
        for more than 4 weeks.
  
        Patients undergo computed tomography (CT) scan or positron emission tomography(PET)/CT scan
        and blood sample collection throughout the study.
  
        After completion of initial radiation therapy, patients follow up at 1 week, 3 months, 6
        months and 12 months and then for an additional year.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Percent of patients on planned protocol treatment
  time frame: At 6 months
  description: Patient counts and percentages will be provided.
  measure: Rate of all grades and grade >= 3 adverse events at least possibly related to study therapy
  time frame: Up to 2 years
  description: As measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Observed toxicities will be summarized, for all patients in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
  measure: Overall survival
  time frame: From the date of study enrollment to the date of death from any cause, up to 2 years
  description: Will be estimated using the product-limit method of Kaplan-Meier. Two-sided 95% confidence intervals will be computed.
  measure: Change in quality of life (QOL)
  time frame: From baseline to 3 months post initial stereotactic body radiation therapy (SBRT)
  description: As measured by Functional Assessment of Cancer Therapy-General (FACT-G) v4. Repeated QOL assessments will be tabulated and graphically displayed to describe the changes of QOL outcomes over time.
  measure: Change in fludeoxyglucose (FDG) uptake
  time frame: From baseline to completion of SBRT, up to 2 years
  description: As measured by metabolic tumor volume and total lesion glycolysis at each fraction. Will be analyzed using independent student's t-test to compare normal variables and non-parametric tests including Wilcoxon's signed-rank test for paired data will be used to compare non-normally distributed variables. Repeated measures analysis of variance (ANOVA) will be used to test for differences at more than one time point. Correlation between metabolic tumor volume, total lesion glycolysis and circulating tumor deoxyribonucleic acid (ctDNA) and time to treatment failure (as described above) as well as overall survival will be explored using univariate and multivariate Cox regression.
  measure: Ratio of patients achieving local control and distant control
  time frame: Up to 2 years
  measure: First occurrence of disease progression
  time frame: From study entry to first occurrence of disease progression, up to 2 years
  description: By Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) v1.0 or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A progressive event will occur when: more than five sites of progression based on PERCIST or RECIST, inability to receive more biologically guided radiation therapy (BgRT)/SBRT or osimertinib, physician decision to come off study or change therapy, patient withdrawal of consent or death will all be considered events. Will be estimated using the product-limit method of Kaplan-Meier.
  measure: Time to treatment failure
  time frame: From study entry to treatment failure, up to 2 years
  description: Will be estimated using the product-limit method of Kaplan-Meier. For time to treatment failure, a progressive event will occur when: more than five sites of progression based on PERCIST or RECIST, inability to receive more BgRT/SBRT or osimertinib, physician decision to come off study or change therapy, patient withdrawal of consent or death will all be considered events.
  measure: Ratio of patients needing salvage BgRT/SBRT
  time frame: Up to 1 year
  arm group label: Treatment (BgRT/SBRT)
  arm group type: Experimental
  description: Patients continue to receive osimertinib PO QD in the absence of unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients then continue to receive osimertinib and are monitored via imaging. If additional progression is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the absence of > 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib for more than 4 weeks.
  Patients undergo CT scan or PET/CT scan and blood sample collection throughout the study.
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Treatment (BgRT/SBRT)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo CT or PET/CT scan
  arm group label: Treatment (BgRT/SBRT)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Drug
  intervention name: Osimertinib
  description: Given PO
  arm group label: Treatment (BgRT/SBRT)
  other name: AZD-9291
  other name: AZD9291
  other name: Mereletinib
  other name: Tagrisso
  intervention type: Procedure
  intervention name: Positron Emission Tomography
  description: Undergo PET/CT
  arm group label: Treatment (BgRT/SBRT)
  other name: Medical Imaging, Positron Emission Tomography
  other name: PET
  other name: PET Scan
  other name: Positron emission tomography (procedure)
  other name: Positron Emission Tomography Scan
  other name: Positron-Emission Tomography
  other name: proton magnetic resonance spectroscopic imaging
  other name: PT
  intervention type: Radiation
  intervention name: Stereotactic Body Radiation Therapy
  description: Undergo BgRT/SBRT
  arm group label: Treatment (BgRT/SBRT)
  other name: SABR
  other name: SBRT
  other name: Stereotactic Ablative Body Radiation Therapy
  intervention type: Other
  intervention name: Survey Administration
  description: Ancillary study
  arm group label: Treatment (BgRT/SBRT)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Arya Amini
  role: Principal Investigator
  affiliation: City of Hope Medical Center
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Osimertinib