<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/NCT03758287</url>
  </required_header>
  <id_info>
    <org_study_id>PCD-DCT053-16-001</org_study_id>
    <nct_id>NCT03758287</nct_id>
  </id_info>
  <brief_title>Ningetinib (CT053PTSA) Plus Gefitinib in Stage IIIB or IV NSCLC Patients With EGFR Mutation and T790M Negative</brief_title>
  <official_title>A Phase Ib, Multi-center, Open Label Study of Ningetinib (CT053PTSA) in Combination With Gefitinib in Stage IIIB or IV NSCLC Patients With EGFR Mutation and T790M Negative Who Have Progressed After EGFR TKI Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunshine Lake Pharma Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunshine Lake Pharma Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase Ib, multi-center, open label study evaluating the safety and efficacy of&#xD;
      CT053PTSA in combination with gefitinib in patients with EGFR mutation, T790M negative NSCLC&#xD;
      who have progressed after EGFR TKI treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is being carried out in two parts, part 1 and part 2.&#xD;
&#xD;
      Part 1: This is the dose-escalation part. The primary purpose of the part 1 portion is to&#xD;
      determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommend&#xD;
      the appropriate doses of CT053PTSA in combination with gefitinib for further studies.&#xD;
&#xD;
      Part 2: This is the expansion part. The part 2 portion of this study will continue to&#xD;
      evaluate the safety and efficacy of the combination of CT053PTSA and gefitinib , at the&#xD;
      appropriate doses recommended in Part 1, in patients with EGFR mutation, T790M negative&#xD;
      NSCLC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Anticipated">July 17, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 17, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>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>Part 1（dose-escalation part）: Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Cycle 1 Day 1 to Cycle 1 Day 28</time_frame>
    <description>The maximum tolerated dose (MTD) of the CT053PTSA and gefitinib combination will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAE v4.03</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2（expansion part）: Overall Response Rate</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>Overall response rate (ORR), defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors as assessed by RECIST v1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events (AEs) as a measure of safety and tolerability</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>Safety and tolerability will be assessed through AEs, via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>DCR, proportion of patients with best overall response of CR, PR or SD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>PFS, defined as time from date of treatment to disease progression or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>up to approximately 36 months</time_frame>
    <description>DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>up to approximately 60 months</time_frame>
    <description>OS, defined as time from date of treatment to death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>Cycle 1 Day1 and Day 28</time_frame>
    <description>to assess the pharmacokinetic profile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum observed plasma concentration (Tmax)</measure>
    <time_frame>Cycle 1 Day1 and Day 28</time_frame>
    <description>to assess the pharmacokinetic profile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration time curve (AUC)</measure>
    <time_frame>Cycle 1 Day1 and Day 28</time_frame>
    <description>to assess the pharmacokinetic profile</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">158</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>CT053PTSA +Gefitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive CT053PTSA and gefitinib over a 28-day cycle until progressive disease, intolerable toxicity or subject's withdrawal from treatment.&#xD;
CT053PTSA will be administered daily, at a dose of 30 mg/40mg/60mg orally .&#xD;
Gefitinib will be administered daily, at a dose of 250 mg orally .</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CT053PTSA</intervention_name>
    <arm_group_label>CT053PTSA +Gefitinib</arm_group_label>
    <other_name>Ningetinib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gefitinib</intervention_name>
    <arm_group_label>CT053PTSA +Gefitinib</arm_group_label>
    <other_name>Iressa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed Stage IIIB or IV NSCLC&#xD;
&#xD;
          -  Resistance to EGFR TKI (1st, 2nd or 3rd generation)&#xD;
&#xD;
          -  Histological or cytological evidence of EGFR mutation and T790M negative after&#xD;
             progression on last EGFR TKI therapy&#xD;
&#xD;
          -  c-Met GCN ≥ 6 or cluster amplification is required if participant is resistant to1st&#xD;
             or 2nd generation EGFR-TKI ;c-MET GCN statue is not required, If participant is&#xD;
             resistant to3rd generation EGFR-TKI （osimertinib）；&#xD;
&#xD;
          -  Measurable disease according to Response Evaluation Criteria in Solid Tumors version&#xD;
             1.1 (RECIST 1.1)&#xD;
&#xD;
          -  Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except&#xD;
             alopecia)&#xD;
&#xD;
          -  ECOG performance status (PS) 0 or 1&#xD;
&#xD;
          -  Life expectancy of ≥ 12 weeks&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatments&#xD;
&#xD;
               -  Chemotherapy, targeted therapy (except EGFR TKI), immunotherapy, radiotherapy, or&#xD;
                  major surgery within 4 weeks prior to study treatment&#xD;
&#xD;
               -  Nitrosourea and mitomycin chemotherapy within 6 weeks prior to study treatment&#xD;
&#xD;
               -  EGFR TKI treatment within 2 weeks prior to study treatment&#xD;
&#xD;
               -  Had received live vaccine within 4 weeks prior to study treatment&#xD;
&#xD;
               -  Had received any investigational agent from other clinical study within 4 weeks&#xD;
                  prior to study treatment or are currently participating in other clinical trials&#xD;
&#xD;
               -  Previous treatment with any other c-MET inhibitor or Axl inhibitor (eg,&#xD;
                  crizotinib, cabozantinib, volitinib, INC280)&#xD;
&#xD;
          -  Symptomatic, untreated or unstable central nervous system metastases&#xD;
&#xD;
          -  Spinal cord compression, carcinomatous meningitis or leptomeningeal diseaseonly&#xD;
             (patient are only permitted if treated, asymptomatic and stable for at least 4 weeks&#xD;
             prior to start of study treatment)&#xD;
&#xD;
          -  Interstitial pneumonia or radiation pneumonitis&#xD;
&#xD;
          -  Uncontrolled hypertension that require more than two anti-hypertensive agents to&#xD;
             control, or systolic blood pressure (BP) &gt;140mmHg or diastolic BP &gt;90 mmHg before the&#xD;
             first administration (BP is the mean blood pressure of two measures that 1 hours&#xD;
             interval or above)&#xD;
&#xD;
          -  Doppler ultrasound evaluation：Left ventricular ejection fraction &lt; 50%&#xD;
&#xD;
          -  Grade ≥ 2 of arrhythmia (assessed by NCI CTCAE 4.03), or symptomatic bradycardia, or&#xD;
             male with QTCF &gt; 450 ms or female with QTCF &gt; 470 ms, or patients with a history of&#xD;
             torsion or congenital QT prolonged syndrome long QT syndrome&#xD;
&#xD;
          -  Certain factors that would preclude adequate absorption of CT053PTSA and gefitinib&#xD;
             (eg. unable to swallow, chronic diarrhea, intestinal obstruction)&#xD;
&#xD;
          -  Significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis&#xD;
             volume is 2.5 ml or above&#xD;
&#xD;
          -  Patients with evidence of bleeding tendency, including the following cases:&#xD;
             gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above;&#xD;
             or melena or hematemesis within 2 months; or visceral bleeding that may occur&#xD;
             considered by investigator&#xD;
&#xD;
          -  History of immunodeficiency, or other acquired or congenital immunodeficiency, or&#xD;
             history of organ transplantation&#xD;
&#xD;
          -  Any disease of the following bellowed within 12 months prior to administration:&#xD;
             Myocardial infarction, severe angina, or unstable angina, coronary or peripheral&#xD;
             artery bypass graft, congestive heart failure, or cerebrovascular events (including&#xD;
             transient ischemic attack)&#xD;
&#xD;
          -  Pulmonary embolism within 6 months prior to administration&#xD;
&#xD;
          -  Active infection of hepatitis B, or infection of HIV&#xD;
&#xD;
          -  Other malignancies within 5 years prior to enrollment, with the exception of carcinoma&#xD;
             in situ of the cervix, basal or squamous cell skin cancer&#xD;
&#xD;
          -  History of thyroid dysfunction, and the thyroid function cannot be maintained at the&#xD;
             normal range with drugs.&#xD;
&#xD;
          -  Serious electrolyte imbalance in the investigator's judgment&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  Any other reason the investigator considers the patient is not suitable to participate&#xD;
             in the study&#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>Li Zhang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>June 20, 2022</last_update_submitted>
  <last_update_submitted_qc>June 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2022</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>Gefitinib</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/NCT03758287
org study id: PCD-DCT053-16-001
nct id: NCT03758287
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a phase Ib, multi-center, open label study evaluating the safety and efficacy of
      CT053PTSA in combination with gefitinib in patients with EGFR mutation, T790M negative NSCLC
      who have progressed after EGFR TKI treatment.
This study is being carried out in two parts, part 1 and part 2.

      Part 1: This is the dose-escalation part. The primary purpose of the part 1 portion is to
      determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommend
      the appropriate doses of CT053PTSA in combination with gefitinib for further studies.

      Part 2: This is the expansion part. The part 2 portion of this study will continue to
      evaluate the safety and efficacy of the combination of CT053PTSA and gefitinib , at the
      appropriate doses recommended in Part 1, in patients with EGFR mutation, T790M negative
      NSCLC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part 1（dose-escalation part）: Maximum Tolerated Dose (MTD)
time frame: Cycle 1 Day 1 to Cycle 1 Day 28
description: The maximum tolerated dose (MTD) of the CT053PTSA and gefitinib combination will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAE v4.03
measure: Part 2（expansion part）: Overall Response Rate
time frame: up to approximately 36 months
description: Overall response rate (ORR), defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors as assessed by RECIST v1.1
measure: Number of patients with adverse events (AEs) as a measure of safety and tolerability
time frame: up to approximately 36 months
description: Safety and tolerability will be assessed through AEs, via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs
measure: Disease Control Rate (DCR)
time frame: up to approximately 36 months
description: DCR, proportion of patients with best overall response of CR, PR or SD
measure: Progression-free Survival (PFS)
time frame: up to approximately 36 months
description: PFS, defined as time from date of treatment to disease progression or death due to any cause
measure: Duration of Response (DOR)
time frame: up to approximately 36 months
description: DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause
measure: Overall Survival (OS)
time frame: up to approximately 60 months
description: OS, defined as time from date of treatment to death due to any cause
measure: Maximum observed plasma concentration (Cmax)
time frame: Cycle 1 Day1 and Day 28
description: to assess the pharmacokinetic profile
measure: Time of maximum observed plasma concentration (Tmax)
time frame: Cycle 1 Day1 and Day 28
description: to assess the pharmacokinetic profile
measure: Area under the plasma concentration time curve (AUC)
time frame: Cycle 1 Day1 and Day 28
description: to assess the pharmacokinetic profile
arm group label: CT053PTSA +Gefitinib
arm group type: Experimental
description: Patients will receive CT053PTSA and gefitinib over a 28-day cycle until progressive disease, intolerable toxicity or subject's withdrawal from treatment.
CT053PTSA will be administered daily, at a dose of 30 mg/40mg/60mg orally .
Gefitinib will be administered daily, at a dose of 250 mg orally .
intervention type: Drug
intervention name: CT053PTSA
arm group label: CT053PTSA +Gefitinib
other name: Ningetinib
intervention type: Drug
intervention name: Gefitinib
arm group label: CT053PTSA +Gefitinib
other name: Iressa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Li Zhang, MD
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Gefitinib
sharing ipd: No