<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/NCT02972333</url>
  </required_header>
  <id_info>
    <org_study_id>APOLLO</org_study_id>
    <nct_id>NCT02972333</nct_id>
  </id_info>
  <brief_title>Open Label, Prospective Study to Investigate Efficacy and Safety of AZD9291 in BM From NSCLC Patients With EGFR T790M</brief_title>
  <official_title>Open Label, Multi-center, Prospective Study to Investigate the Efficacy and Safety of AZD9291 in Brain Metastases From Patients With EGFR T790M Positive NSCLC Who Have Received Prior Therapy With an EGFR-TKI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shandong Cancer Hospital and Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shandong Cancer Hospital and Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study aims to investigate the efficacy and safety of AZD9291 in brain metastases from&#xD;
      patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with confirmed EGFR T790M positive NSCLC who have received prior therapy with an&#xD;
      EGFR-TKI and concurrent with brain metastasis will be enrolled into the study. All eligible&#xD;
      patients will have access to AZD9291 regimen through the ASTRIS study as long as they&#xD;
      continue to show clinical benefit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">September 2019</primary_completion_date>
  <phase>Phase 3</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>PFSo (overall progression free survival)</measure>
    <time_frame>2 years</time_frame>
    <description>To assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI by PFSo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFSe (extracranial progression-free survival)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFSi (intracranial progression-free survival)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORRo (overall objective response rate)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORRe (extracranial objective response rate)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORRi (intracranial objective response rate)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCRo (overall disease control rate)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCRe (extracranial disease control rate)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCRi (intracranial disease control rate)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DoRo (overall duration of response)</measure>
    <time_frame>3 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DoRe (extracranial duration of response)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DoRi (intracranial duration of response)</measure>
    <time_frame>2 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS(overall survival)</measure>
    <time_frame>3 years</time_frame>
    <description>To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events/Serious adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the safety and tolerability profile of AZD9291 and subgroups such as AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy and etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QoL</measure>
    <time_frame>2 years</time_frame>
    <description>To assess disease-related symptoms and QoL in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>2 years</time_frame>
    <description>To assess disease-related symptoms and cognitive function in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>T790M mutation positive rate</measure>
    <time_frame>2 years</time_frame>
    <description>To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.</description>
  </other_outcome>
  <other_outcome>
    <measure>Concordance of T790M status between CSF and plasma</measure>
    <time_frame>2 years</time_frame>
    <description>To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change of imputed ctDNA concentration before and after treatment</measure>
    <time_frame>2 years</time_frame>
    <description>To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of each genetic mutation</measure>
    <time_frame>2 years</time_frame>
    <description>To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline in glucose and protein levels</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline in tumor cell count</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology.</description>
  </other_outcome>
  <other_outcome>
    <measure>AZD9291 concentration level in CSF/plasma</measure>
    <time_frame>2 years</time_frame>
    <description>To explore potential relation between relevant efficacy measures, biomarkers or safety variables and plasma or CSF concentration of AZD9291 (or metabolites).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>EGFR-TKI Resistant Mutation</condition>
  <condition>Nonsmall Cell Lung Cancer</condition>
  <condition>AZD9291</condition>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>AZD9291 80mg oral each day±RT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AZD9291(80mg, QD, p.o.) was provided to patients with confirmed EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI and concurrent with brain metastasis. Radiation therapy will be implemented according to investigator's clinical practice(A 7-10 days washout period before radiotherapy and 1 week period after completion of brain radiothearpy before re-starting AZD9291.).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD9291 80mg oral each day</intervention_name>
    <description>All eligible patients will have access to AZD9291 regimen through the ASTRIS study as long as they continue to show clinical benefit.</description>
    <arm_group_label>AZD9291 80mg oral each day±RT</arm_group_label>
    <other_name>AZD9291, 80mg, QD, p.o. (2nd line or later)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation therapy</intervention_name>
    <description>Radiation therapy will be implemented according to investigator's clinical practice.Based on the guidelines provided for the interruption of ADZ9291 with brain radiation therapy, a 7-10 days washout period before radiotherapy and 1 week period after completion of brain radiothearpy before re-starting AZD9291.</description>
    <arm_group_label>AZD9291 80mg oral each day±RT</arm_group_label>
    <other_name>WBRT or SRS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of signed and dated written informed consent by the patient or legally&#xD;
             acceptable representative prior to any study-specific procedures&#xD;
&#xD;
          2. Metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy,&#xD;
             with confirmation of the presence of the T790M mutation.&#xD;
&#xD;
          3. For patients with LM: Confirmed diagnosis of LM by positive CSF cytology. Diagnosis by&#xD;
             MRI only is not eligible for study entry. At least one site of CNS leptomeningeal&#xD;
             disease that can be assessed by magnetic resonance imaging (MRI) and which is suitable&#xD;
             for repeat assessments. Measurable CNS or extracranial disease is not required.&#xD;
&#xD;
          4. For patients with measurable BM but without LM: At least one measurable intracranial&#xD;
             lesion that, if previously irradiated, has progressed or not responded to radiation&#xD;
             therapy, that can be accurately measured at baseline as ≥ 10 mm in the longest&#xD;
             diameter by magnetic resonance imaging (MRI) and which is suitable for accurate&#xD;
             repeated measurements. Measurable extracranial disease is not required.&#xD;
&#xD;
          5. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of&#xD;
             treatment.&#xD;
&#xD;
          6. World Health Organization (WHO) performance status 0-2 with no deterioration over the&#xD;
             previous 2 weeks and a minimum life expectancy of 3 months.&#xD;
&#xD;
          7. Adequate bone marrow reserve and organ function as demonstrated by complete blood&#xD;
             count, biochemistry in blood and urine at baseline.&#xD;
&#xD;
          8. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion&#xD;
             criterion #10.&#xD;
&#xD;
          9. Female patients of childbearing potential must be using adequate contraceptive&#xD;
             measures (see Restrictions, Section 3.5), must not be breast feeding, and must have a&#xD;
             negative pregnancy test prior to start of dosing. Otherwise, they must have evidence&#xD;
             of nonchild bearing potential as defined below:&#xD;
&#xD;
               1. Post-menopausal defined as aged more than 50 years and amenorrheic for at least&#xD;
                  12 months following cessation of all exogenous hormonal treatments&#xD;
&#xD;
               2. Women less than 50 years would be consider post-menopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and with luteinizing hormone and follicle-stimulating hormone levels&#xD;
                  in the post-menopausal range for the institution&#xD;
&#xD;
               3. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral&#xD;
                  oophorectomy or bilateral salpingectomy but not tubal ligation&#xD;
&#xD;
         10. Male patients must be willing to use barrier contraception, i.e., condoms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects should not enter the study if any of the following exclusion criteria are&#xD;
        fulfilled:&#xD;
&#xD;
          1. Previous (within 6 months) or current treatment with AZD9291&#xD;
&#xD;
          2. Patients currently receiving (or unable to stop use at least 1 week prior to receiving&#xD;
             the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of&#xD;
             cytochrome P450 (CYP) 3A4 (Appendix B)&#xD;
&#xD;
          3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled&#xD;
             hypertension, active bleeding diatheses, active infection* including hepatitis B,&#xD;
             hepatitis C and human immunodeficiency virus, or significantly impaired bone marrow&#xD;
             reserve or organ function, including hepatic and renal impairment, which in the&#xD;
             investigator's opinion would significantly alter the risk/benefit balance.&#xD;
&#xD;
             * active infection will include any patients receiving intravenous treatment for any&#xD;
             infection and patients with hepatitis B or C surface antigen (+) - Patients receiving&#xD;
             oral antiviral suppressive therapy for hepatitis B or C will be permitted to enrol in&#xD;
             the study.&#xD;
&#xD;
          4. Patient with symptomatic central nervous system (CNS) metastases who is neurologically&#xD;
             unstable or has required increasing doses of steroids to manage CNS symptoms within&#xD;
             the 2 weeks prior to start AZD9291 administration.&#xD;
&#xD;
          5. Prior whole brain radiation therapy.&#xD;
&#xD;
          6. Known intracranial hemorrhage which is unrelated to tumor.&#xD;
&#xD;
          7. For patients with LM and/or BM, CNS complications that require urgent neurosurgical&#xD;
             intervention (e.g. resection or shunt placement).&#xD;
&#xD;
          8. For patients with LM, inability to undergo collection of CSF.&#xD;
&#xD;
          9. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid&#xD;
             treatment, or any evidence of clinically active ILD&#xD;
&#xD;
         10. Any of the following cardiac criteria:&#xD;
&#xD;
               1. Mean resting corrected QT interval (QTcF) &gt; 470 ms using Fredericia's formula :&#xD;
&#xD;
               2. Any clinically important abnormalities in rhythm, conduction or morphology of&#xD;
                  resting ECG (e.g., complete left bundle branch block, third degree heart block,&#xD;
                  second degree heart block)&#xD;
&#xD;
               3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic&#xD;
                  events&#xD;
&#xD;
         11. Any unresolved toxicity from prior therapy CTCAE &gt; grade 3 at the time of starting&#xD;
             treatment&#xD;
&#xD;
         12. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar&#xD;
             chemical structure or class to AZD9291&#xD;
&#xD;
         13. Inadequate bone marrow reserve or organ function as demonstrated by any of the&#xD;
             following laboratory values:&#xD;
&#xD;
               -  Absolute neutrophil count &lt; 1.5 x 10^9/L&#xD;
&#xD;
               -  Platelet count &lt; 100 x 10^9/L&#xD;
&#xD;
               -  Haemoglobin &lt; 90 g/L&#xD;
&#xD;
               -  Alanine aminotransferase &gt; 2.5 times the upper limit of normal (ULN) if no&#xD;
                  demonstrable liver metastases or &gt; 5 times ULN in the presence of liver&#xD;
                  metastases&#xD;
&#xD;
               -  Aspartate aminotransferase &gt; 2.5 times ULN if no demonstrable liver metastases or&#xD;
                  &gt; 5 times ULN in the presence of liver metastases&#xD;
&#xD;
               -  Total bilirubin &gt; 1.5 times ULN. Total bilirubin &gt;3 times the ULN in patients&#xD;
                  with documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or in the&#xD;
                  presence of liver metastases&#xD;
&#xD;
               -  Creatinine &gt;1.5 times ULN concurrent with creatinine clearance &lt; 50 mL/min&#xD;
                  (measured or calculated by Cockcroft and Gault equation). Confirmation of&#xD;
                  creatinine clearance is only required when creatinine is &gt;1.5 times ULN.&#xD;
&#xD;
               -  If bone metastases are present and liver function is otherwise considered&#xD;
                  adequate by the investigator then elevated ALP will not exclude the patient.&#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>Jinming Yu, MD.PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shandong Cancer Hospital and Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jinming Yu, MD.PhD.</last_name>
    <phone>0086-531-67626919</phone>
    <email>sdyujinming@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ligang Xing, MD.PhD.</last_name>
    <phone>0086-531-67626819</phone>
    <email>xinglg@medmail.com.cn</email>
  </overall_contact_backup>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>November 20, 2016</last_update_submitted>
  <last_update_submitted_qc>November 20, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 23, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shandong Cancer Hospital and Institute</investigator_affiliation>
    <investigator_full_name>Jinming Yu</investigator_full_name>
    <investigator_title>Dean</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02972333
org study id: APOLLO
nct id: NCT02972333
lead sponsor: 
collaborator: 
has dmc: Yes
The study aims to investigate the efficacy and safety of AZD9291 in brain metastases from
      patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
Patients with confirmed EGFR T790M positive NSCLC who have received prior therapy with an
      EGFR-TKI and concurrent with brain metastasis will be enrolled into the study. All eligible
      patients will have access to AZD9291 regimen through the ASTRIS study as long as they
      continue to show clinical benefit.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFSo (overall progression free survival)
time frame: 2 years
description: To assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI by PFSo
measure: PFSe (extracranial progression-free survival)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: PFSi (intracranial progression-free survival)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: ORRo (overall objective response rate)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: ORRe (extracranial objective response rate)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: ORRi (intracranial objective response rate)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: DCRo (overall disease control rate)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: DCRe (extracranial disease control rate)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: DCRi (intracranial disease control rate)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: DoRo (overall duration of response)
time frame: 3 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: DoRe (extracranial duration of response)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: DoRi (intracranial duration of response)
time frame: 2 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: OS(overall survival)
time frame: 3 years
description: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
measure: Adverse events/Serious adverse events
time frame: 2 years
description: To evaluate the safety and tolerability profile of AZD9291 and subgroups such as AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy and etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
measure: QoL
time frame: 2 years
description: To assess disease-related symptoms and QoL in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
measure: Cognitive function
time frame: 2 years
description: To assess disease-related symptoms and cognitive function in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
measure: T790M mutation positive rate
time frame: 2 years
description: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
measure: Concordance of T790M status between CSF and plasma
time frame: 2 years
description: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
measure: Change of imputed ctDNA concentration before and after treatment
time frame: 2 years
description: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
measure: Proportion of each genetic mutation
time frame: 2 years
description: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
measure: Change from baseline in glucose and protein levels
time frame: 2 years
description: To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology.
measure: Change from baseline in tumor cell count
time frame: 2 years
description: To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology.
measure: AZD9291 concentration level in CSF/plasma
time frame: 2 years
description: To explore potential relation between relevant efficacy measures, biomarkers or safety variables and plasma or CSF concentration of AZD9291 (or metabolites).
arm group label: AZD9291 80mg oral each day±RT
arm group type: Experimental
description: AZD9291(80mg, QD, p.o.) was provided to patients with confirmed EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI and concurrent with brain metastasis. Radiation therapy will be implemented according to investigator's clinical practice(A 7-10 days washout period before radiotherapy and 1 week period after completion of brain radiothearpy before re-starting AZD9291.).
intervention type: Drug
intervention name: AZD9291 80mg oral each day
description: All eligible patients will have access to AZD9291 regimen through the ASTRIS study as long as they continue to show clinical benefit.
arm group label: AZD9291 80mg oral each day±RT
other name: AZD9291, 80mg, QD, p.o. (2nd line or later)
intervention type: Radiation
intervention name: Radiation therapy
description: Radiation therapy will be implemented according to investigator's clinical practice.Based on the guidelines provided for the interruption of ADZ9291 with brain radiation therapy, a 7-10 days washout period before radiotherapy and 1 week period after completion of brain radiothearpy before re-starting AZD9291.
arm group label: AZD9291 80mg oral each day±RT
other name: WBRT or SRS
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jinming Yu, MD.PhD.
role: Principal Investigator
affiliation: Shandong Cancer Hospital and Institute
last name: Jinming Yu, MD.PhD.
phone: 0086-531-67626919
email: sdyujinming@163.com
last name: Ligang Xing, MD.PhD.
phone: 0086-531-67626819
email: xinglg@medmail.com.cn
responsible party type: Principal Investigator
investigator affiliation: Shandong Cancer Hospital and Institute
investigator full name: Jinming Yu
investigator title: Dean
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Osimertinib
sharing ipd: No