<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/NCT02973763</url>
  </required_header>
  <id_info>
    <org_study_id>20161121</org_study_id>
    <nct_id>NCT02973763</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Alflutinib in Advanced Non Small Cell Lung Cancer</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Alflutinib in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allist Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allist Pharmaceuticals, Inc.</source>
  <brief_summary>
    <textblock>
      Alflutinib Mesylate Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective&#xD;
      Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation&#xD;
      tumor cell in Xenograft mouse model. This study aims at local advanced or metastatic&#xD;
      non-small cell lung cancer patients with T790M drug-resistant mutation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I study, to evaluate the safety, tolerability, pharmacokinetics and&#xD;
      anti-tumor activity of AST2818 in patients with advanced non-small cell lung cancer who&#xD;
      progressed on prior therapy with an epidermal growth factor receptor tyrosine kinase&#xD;
      inhibitor agent. The tolerability of AST2818 20 mg/day - 240 mg/day in 14 subjects was&#xD;
      observed. 7-days observation period for a single dose and 21-days observation period for&#xD;
      multiple doses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 30, 2016</start_date>
  <completion_date type="Anticipated">August 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2020</primary_completion_date>
  <phase>Phase 1</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>Incidence and Severity of Treatment-Emergent Adverse Events</measure>
    <time_frame>Adverse events will be collected from baseline until 28 days after the last dose</time_frame>
    <description>Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations, RECIST1.1, and NCI CTCAE v4.03</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration [Cmax] of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Time [tmax] of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out tmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day1 to figure out AUC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out terminal rate constant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out clearance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half life of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out half life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out volume of distribution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean resistance time of single dose Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out mean resistance time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady state Cmax of multiple doses Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Cmax of Alflutinib and 2 metabolites at steady state following multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady state tmax of multiple doses Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>tmax of Alflutinib and 2 metabolites at steady state following multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady state Cmin (Minimum Plasma Concentration) of multiple doses Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Cmin of Alflutinib and 2 metabolites at steady state following multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady state AUC of multiple doses Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>AUC of Alflutinib and 2 metabolites at steady state following multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady state clearance of multiple doses Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Clearance of Alflutinib and 2 metabolites at steady state following multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio of multiple doses Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Accumulation ratio of Alflutinib and 2 metabolites following multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time dependency of multiple doses Alflutinib and 2 metabolites</measure>
    <time_frame>Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)</time_frame>
    <description>Time dependency of Alflutinib and 2 metabolites following multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate of Alflutinib</measure>
    <time_frame>CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months</time_frame>
    <description>Evaluation of objective response rate assessed by RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response of Alflutinib</measure>
    <time_frame>CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months</time_frame>
    <description>Duration of response assessed by RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival of Alflutinib</measure>
    <time_frame>CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months</time_frame>
    <description>Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease progression rate of Alflutinib</measure>
    <time_frame>CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months</time_frame>
    <description>Progression of tumor was assessed by RECIST 1.1 thereby to evaluate disease progression rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate of Alflutinib</measure>
    <time_frame>CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months</time_frame>
    <description>Clinical benefit rate was calculated by adding up complete remission, partial remission and stabilization of disease assessed by RECIST 1.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>Alflutinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients take Alflutinib orally once per day at different dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alflutinib</intervention_name>
    <arm_group_label>Alflutinib</arm_group_label>
    <other_name>AST2818</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients of either gender, aged from 18 years older to 65.&#xD;
&#xD;
          2. Histologically or cytologically confirmed metastatic, or unresectable locally&#xD;
             advanced, recurrent NSCLC.&#xD;
&#xD;
          3. Radiological documentation of disease progression while on a previous continuous&#xD;
             treatment with an EGFR TKI e.g. gefitinib or erlotinib or Afatinib, or Icotinib (Third&#xD;
             EGFR TKI are not included). In addition other lines of therapy may have been given.&#xD;
&#xD;
          4. Confirmation that the tumour harbours an EGFR mutation known to be associated with&#xD;
             EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q&#xD;
             mutation)&#xD;
&#xD;
          5. Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease&#xD;
             progression on the most recent treatment regimen (irrespective of whether this is EGFR&#xD;
             TKI or chemotherapy).&#xD;
&#xD;
          6. ECOG performance status of 0 to 2. Life expectancy of at least 12 weeks.&#xD;
&#xD;
          7. At least one measurable disease by CT or PET-CT or MRI, according to RECIST Version&#xD;
             1.1.&#xD;
&#xD;
          8. Organ function must meet the following requirements：&#xD;
&#xD;
               -  Absolute neutrophil count &gt;= 1.5 x 109/L, Platelet count &gt;= 75 x 109/L,&#xD;
                  Haemoglobin &gt;= 90 g/L；&#xD;
&#xD;
               -  Alanine aminotransferase/Aspartate aminotransferase &lt;= 2.5 times the upper limit&#xD;
                  of normal if no demonstrable liver metastases or &lt;= 5 times in the presence of&#xD;
                  liver metastases；&#xD;
&#xD;
               -  Total bilirubin &lt;= 1.5 times ULN if no liver metastases or &lt;= 3 times ULN in the&#xD;
                  presence of liver metastases or liver metastases；&#xD;
&#xD;
               -  Creatinine &lt;=1.5 times ULN concurrent with creatinine clearance &gt;= 50 ml/min&#xD;
                  (measured or calculated by Cockcroft and Gault equation);&#xD;
&#xD;
          9. Females should not be in lactation period and must have a negative pregnancy test&#xD;
             prior to start of dosing; During the whole treatment,all patients should be in the&#xD;
             entire 3 months during and after the treatment, repeated barrier precautions&#xD;
&#xD;
         10. Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior&#xD;
             to any study-specific evaluation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any cytotoxic chemotherapy from a previous treatment regimen or clinical study within&#xD;
             21 days，Any Target cancer drug from a previous treatment regimen or clinical study&#xD;
             within 14 days, or less than approximately 5x half-life of the first dose of study&#xD;
             treatment；&#xD;
&#xD;
          2. The third EGFR-TKI from a previous treatment regimen or clinical study (ie, AZD9291,&#xD;
             CO-1686, HM61713, ASP8273, EGF816, avitinib,&#xD;
&#xD;
          3. Taking (or cannot stop taking 1 week before the first dose receiving) strong inhibitor&#xD;
             of CYP3A4 or antitumor herb.&#xD;
&#xD;
          4. Unrecovered toxic reaction due to former therapy existed, with over 1 grade of CTCAE&#xD;
             (except alopecia) or 2 grade if ever applied DDP curing related neuropathy.&#xD;
&#xD;
          5. Spinal compression, or brain metastasis exhibiting symptoms but untreated (except&#xD;
             those exhibit no symptom with stable condition and do not apply corticosteroids for 4&#xD;
             weeks before the trail initiating)&#xD;
&#xD;
          6. Any evidence showing severe or inadequate controlled systemic disease. For example&#xD;
             patients with inadequate controlled hypertension considered not suitable for the trail&#xD;
             or would affect the compliance towards the protocol, with active hemorrhagic tendency,&#xD;
             with active infection such as HBV (HBV-DNA≥1000cps/ml), with HCV, with HIV et al&#xD;
             (except for HBV carrier those the researcher considered meet the criterion).&#xD;
&#xD;
          7. Any condition affecting the drug taking, or significantly affecting the absorption or&#xD;
             the pharmacokinetic parameters, include any kind of uncontrollable nausea or vomit,&#xD;
             chronic gastroenteropathy, disability in swallowing, and history of gastrointestinal&#xD;
             resection or surgery.&#xD;
&#xD;
          8. Any condition meet the following cardiac standard: ECG show a QTc&gt;470 msec under&#xD;
             resting state (Repeat in 48 hours when a first abnormal discovered, take mean of the&#xD;
             two measurements). All kinds of abnormal in cardiac rhythm, conduction and resting ECG&#xD;
             profile with clinical significance, for example complete left bundle branch block, 2&#xD;
             or 3 grade of conduction block and a PR interval&gt;250 msec. Any possible factors&#xD;
             increasing the risk of QTc extending or leading to arrhythmia, such as heart failure,&#xD;
             hypokalemia, congenital long QT syndrome, any first degree relative suffered from long&#xD;
             QT syndrome or undertook unexplained sudden death before 40 years old, or taking any&#xD;
             drug leading to a longer QTc.&#xD;
&#xD;
          9. Any history of interstitial lung disease, drug induced interstitial lung disease,&#xD;
             radiation pneumonia require steroid therapy or active interstitial lung disease with&#xD;
             clinical evidence during recruiting.&#xD;
&#xD;
         10. Patients with other factors the researchers considered not suitable for the trail (for&#xD;
             example, patients those who not willing to follow the procedure, limitation or&#xD;
             requirements, who once experienced bone marrow allotransplantation, who have other&#xD;
             kinds of malignant tumor coexisted or who showed allergic to the active ingredients or&#xD;
             inactive adjuvant of the investigational drug, as well as drugs with similar chemical&#xD;
             structure or in the same class).&#xD;
&#xD;
         11. Confirmed mutation of EGFR 20 exon insertion at anytime after the first diagnosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shi YK</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>January 2, 2020</last_update_submitted>
  <last_update_submitted_qc>January 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2020</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, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflutinib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02973763
org study id: 20161121
nct id: NCT02973763
lead sponsor: 
Alflutinib Mesylate Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective
      Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation
      tumor cell in Xenograft mouse model. This study aims at local advanced or metastatic
      non-small cell lung cancer patients with T790M drug-resistant mutation.
This is a Phase I study, to evaluate the safety, tolerability, pharmacokinetics and
      anti-tumor activity of AST2818 in patients with advanced non-small cell lung cancer who
      progressed on prior therapy with an epidermal growth factor receptor tyrosine kinase
      inhibitor agent. The tolerability of AST2818 20 mg/day - 240 mg/day in 14 subjects was
      observed. 7-days observation period for a single dose and 21-days observation period for
      multiple doses.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and Severity of Treatment-Emergent Adverse Events
time frame: Adverse events will be collected from baseline until 28 days after the last dose
description: Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations, RECIST1.1, and NCI CTCAE v4.03
measure: Maximum Plasma Concentration [Cmax] of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out Cmax.
measure: Peak Plasma Time [tmax] of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out tmax.
measure: Area under the plasma concentration versus time curve (AUC) of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day1 to figure out AUC.
measure: Terminal rate constant of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out terminal rate constant.
measure: Clearance of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out clearance.
measure: Half life of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out half life.
measure: Volume of distribution of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out volume of distribution.
measure: Mean resistance time of single dose Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Collect plasma concentrations of Alflutinib and 2 metabolites following single dose at designated time points of Day 1 to figure out mean resistance time.
measure: Steady state Cmax of multiple doses Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Cmax of Alflutinib and 2 metabolites at steady state following multiple doses.
measure: Steady state tmax of multiple doses Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: tmax of Alflutinib and 2 metabolites at steady state following multiple doses.
measure: Steady state Cmin (Minimum Plasma Concentration) of multiple doses Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Cmin of Alflutinib and 2 metabolites at steady state following multiple doses.
measure: Steady state AUC of multiple doses Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: AUC of Alflutinib and 2 metabolites at steady state following multiple doses.
measure: Steady state clearance of multiple doses Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Clearance of Alflutinib and 2 metabolites at steady state following multiple doses.
measure: Accumulation ratio of multiple doses Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Accumulation ratio of Alflutinib and 2 metabolites following multiple doses.
measure: Time dependency of multiple doses Alflutinib and 2 metabolites
time frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)
description: Time dependency of Alflutinib and 2 metabolites following multiple doses.
measure: Objective response rate of Alflutinib
time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months
description: Evaluation of objective response rate assessed by RECIST 1.1
measure: Duration of response of Alflutinib
time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months
description: Duration of response assessed by RECIST 1.1
measure: Progression free survival of Alflutinib
time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months
description: Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival
measure: Disease progression rate of Alflutinib
time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months
description: Progression of tumor was assessed by RECIST 1.1 thereby to evaluate disease progression rate
measure: Clinical benefit rate of Alflutinib
time frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months
description: Clinical benefit rate was calculated by adding up complete remission, partial remission and stabilization of disease assessed by RECIST 1.1
arm group label: Alflutinib
arm group type: Experimental
description: patients take Alflutinib orally once per day at different dose
intervention type: Drug
intervention name: Alflutinib
arm group label: Alflutinib
other name: AST2818
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Shi YK
role: Principal Investigator
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Aflutinib