<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/NCT03823807</url>
  </required_header>
  <id_info>
    <org_study_id>SHC013-II-01</org_study_id>
    <nct_id>NCT03823807</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety and Efficacy of SH-1028 in Locally Advanced or Metastatic NSCLC</brief_title>
  <official_title>A Multicenter, Open-label, Phase II Study to Evaluate the Safety and Efficacy of SH-1028 in Locally Advanced or Metastatic NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanjing Sanhome Pharmaceutical, Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanjing Sanhome Pharmaceutical, 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>
      A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of SH-1028 with&#xD;
      Locally Advanced/Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with&#xD;
      Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours&#xD;
      harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-label, phase II study to evaluate the safety and efficacy of&#xD;
      SH-1028 in locally advanced or metastatic NSCLC.The trail is divided into two parts:part A is&#xD;
      dose extension phase,and Part B is expand sample size phase to confirm the efficacy of&#xD;
      SH-1028.Patients must agree to provide a biopsy for central confirmation of T790M mutation&#xD;
      status following confirmed disease progression on the most recent treatment regimen. The&#xD;
      primary objective of the study is to assess the efficacy of SH-1028 by assessment of&#xD;
      Objective Response Rate according to RECIST 1.1 by an Independent Central Review.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 2019</start_date>
  <completion_date type="Anticipated">March 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Objective Response Rate (ORR)</measure>
    <time_frame>Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>From Baseline up to 30 days after the last dose, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax）</measure>
    <time_frame>Part A: Day 1 of Cycle 1 and 2 (21 days for 1 cycle).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve [AUC]</measure>
    <time_frame>Part A: Day 1 of Cycle 1 and 2 (21 days for 1 cycle).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Every 2 cycles (21 days for 1 cycle) until end of follow-up, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response(DOR)</measure>
    <time_frame>Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rates(DCR)</measure>
    <time_frame>Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival(OS)</measure>
    <time_frame>Every 2 cycles (21 days for 1 cycle) until end of treatment; Every 12 weeks until end of follow-up, an average of 2 years.</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Biomakers (eg. AF value of KRAS，MET mutation or other gene mutations ) of drug-resistance measured by next-generation sequencing (NGS).</measure>
    <time_frame>at end of treatment，an average of 1 years.</time_frame>
    <description>optional，use NGS to analyse the gene associated with NSCLC and to determine the reason of SH-1028-resistance.</description>
  </other_outcome>
  <other_outcome>
    <measure>Minimum Plasma Concentration (Cmin）</measure>
    <time_frame>Before administration in Day 1 of cycle 2, 3 and 5 (21 days for 1 cycle).</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>SH-1028</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>QD,Oral</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SH-1028</intervention_name>
    <description>Oral,100mg or 200mg ,QD, fasted</description>
    <arm_group_label>SH-1028</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years, both sexes.&#xD;
&#xD;
          -  Histological or cytological confirmation of metastatic or locally advanced, relapsed&#xD;
             NSCLC that are not candidates for curative treatment.&#xD;
&#xD;
          -  Confirmation that the tumor harbors an EGFR mutation known to be associated with&#xD;
             EGFR-TKI sensitivity (including exon 19 deletion, L858R, L861Q, G719X or dual&#xD;
             mutation) for treatment-naive NSCLC patients (without systemic therapy or with relapse&#xD;
             after previous surgery; patients with locally treatment for non-target lesions are&#xD;
             accepted ).(This criteria applies to treatment-naïve NSCLC patients in Part B).&#xD;
&#xD;
          -  Patients must have confirmation of T790M+ mutation status, which have experienced&#xD;
             disease progression while on a previous continuous treatment with an EGFR-TKI or&#xD;
             clinical benefit from EGFR-TKI according to the Jackman criteria while on continuous&#xD;
             treatment with an EGFR-TKI (PR/CR, or SD continued ≥6 months); Patients can receive&#xD;
             more than one line of systemic therapy. (This criteria applies to EGFR-T790M+ patients&#xD;
             in Part A and Part B).&#xD;
&#xD;
          -  ECOG score of 0-2 with a minimum life expectancy of 3 months.&#xD;
&#xD;
          -  At least 1 lesion that has not previously been irradiated, that can be accurately&#xD;
             measured at Baseline as ≥ 10mm in the longest diameter (except lymph nodes which must&#xD;
             have short axis ≥ 15mm) with computerized tomography (CT) or magnetic resonance&#xD;
             imaging (MRI), which is suitable for accurately repeated measurements.&#xD;
&#xD;
          -  Adequate bone marrow reserve or organ function as demonstrated by the following&#xD;
             laboratory values: a) absolute neutrophil count ≥ 1.5×109/L; b) platelet count ≥&#xD;
             100×109/L; c) hemoglobin ≥ 90 g/L; d) ALT ≤ 2.5×ULN if no demonstrable liver&#xD;
             metastases, or ALT ≤ 5×ULN in the presence of liver metastases; e) AST ≤ 2.5×ULN if no&#xD;
             demonstrable liver metastases, or AST ≤ 5×ULN in the presence of liver metastases; f)&#xD;
             Total bilirubin ≤ 1.5×ULN if no liver metastases or ≤ 3×ULN in the presence of&#xD;
             documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases;&#xD;
             g) Creatinine ≤ 1.5×ULN, or Creatinine &gt; 1.5×ULN concurrent with creatinine clearance&#xD;
             ≥ 50 ml/min (measured or calculated by the Cockcroft- Gault equation).&#xD;
&#xD;
          -  Females of child-bearing potential should be using adequate contraceptive measures&#xD;
             throughout the study, should not be breast feeding during the study and until 6 months&#xD;
             after completion of study, and must have a negative pregnancy test prior to start of&#xD;
             dosing.&#xD;
&#xD;
          -  Male patients should be willing to use barrier contraception during the study and&#xD;
             until 6 months after completion of study (i.e., condoms).&#xD;
&#xD;
          -  Do not anticipate other clinical trial in 1 month.&#xD;
&#xD;
          -  Patients must sign and date written informed consent prior to admission to the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  EGFR-TKI treatment within 8 days or approximately 5 times the half-life of the&#xD;
             specific drug, whichever is longer, of the first dose study.&#xD;
&#xD;
          -  Any cytotoxic chemotherapy or immunological therapy used for a previous treatment&#xD;
             regimen or clinical study within 21 days of the first dose of study treatment; Any&#xD;
             target therapy(except EGFR-TKIs)and endocrine therapy used for a previous treatment&#xD;
             regimen or clinical study within 14 days of the first dose of study treatment.&#xD;
&#xD;
          -  Ever used the third generation EGFR-TKI, such as Osimertinib, CO-1686, Avitinib,&#xD;
             AST2818, HS-10296.&#xD;
&#xD;
          -  Major surgery within 4 weeks of the first dose of study treatment.&#xD;
&#xD;
          -  Radiotherapy with a limited field of radiation for palliation within 1 week of the&#xD;
             first dose of study treatment, with the exception of patients receiving radiation to&#xD;
             more than 30% of the bone marrow or with a wide field of radiation which must be&#xD;
             completed within 4 weeks of the first dose of study treatment.&#xD;
&#xD;
          -  The patient is currently using (or cannot discontinue at least 1 week before the first&#xD;
             dose of study treatment) a drug or herbal supplement known as a potent inhibitor or&#xD;
             inducer of CYP3A4.&#xD;
&#xD;
          -  Use large doses of glucocorticoids (eg, &gt;10 mg/day prednisone ) or other&#xD;
             immunosuppressive agents within 4 weeks.&#xD;
&#xD;
          -  Any unresolved toxicities from prior therapy greater than Common Terminology Criteria&#xD;
             for Adverse Events (CTCAE), Grade 1, at the time of starting study treatment with the&#xD;
             exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.&#xD;
&#xD;
          -  Spinal cord compression or brain metastases unless asymptomatic, stable, and not&#xD;
             requiring steroids , anticonvulsants and mannitol for at least 4 weeks prior to start&#xD;
             of study treatment.&#xD;
&#xD;
          -  Any evidence of severe or uncontrolled systemic diseases, including uncontrolled&#xD;
             hypertension or active bleeding diatheses, which, in the Investigator's opinion, makes&#xD;
             it undesirable for the patient to participate in the trial.&#xD;
&#xD;
          -  Active infection (e.g., hepatitis B, hepatitis C or human immunodeficiency virus&#xD;
             [HIV]). (HBsAg is positive but HBV-DNA &lt; ULN ,and HCVAb is positive but HCV-RNA&lt;ULN&#xD;
             can be accepted.）.&#xD;
&#xD;
          -  Any of the following cardiac criteria:&#xD;
&#xD;
               1. Mean resting corrected QT interval (QTc) &gt; 470 msec obtained from 3&#xD;
                  electrocardiograms (ECGs), using the Screening clinic ECG machine and&#xD;
                  Fridericia's formula for QT interval correction.&#xD;
&#xD;
               2. Any clinically important abnormalities in rhythm, conduction, or morphology of&#xD;
                  the resting ECG (e.g., complete left bundle branch block, third-degree heart&#xD;
                  block, second-degree heart block, PR interval &gt;250 msec).&#xD;
&#xD;
          -  Past medical history of interstitial lung disease, drug-induced interstitial lung&#xD;
             disease, radiation pneumonitis which required steroid treatment, or any evidence of&#xD;
             clinically active interstitial lung disease.&#xD;
&#xD;
          -  Have any other malignant tumor within five years (except clinically cured cervical&#xD;
             carcinoma in situ, basal cells or squamous epithelial skin cancer).&#xD;
&#xD;
          -  Any seriously abnormal gastrointestinal function would affect uptake, transport and&#xD;
             absorption of the drug, such as inability to swallow the study medication, refractory&#xD;
             nausea and vomiting, previous significant bowel resection, Recurrent diarrhea,&#xD;
             atrophic gastritis (age &lt; 60 years), unhealed serious gastric diseases, Crohn's&#xD;
             disease or ulcerative colitis.&#xD;
&#xD;
          -  History of hypersensitivity to any active or inactive ingredient of SH-1028 or to a&#xD;
             drug with a similar chemical structure or class to SH-1028.&#xD;
&#xD;
          -  Women who are breast feeding.&#xD;
&#xD;
          -  Any disease or condition that, in the opinion of the Investigator, would compromise&#xD;
             the safety of the patient or interfere with study assessments.&#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_contact>
    <last_name>Caicun Zhou, MD</last_name>
    <phone>+86-13301825532</phone>
    <email>caicunzhoudr@163.com</email>
  </overall_contact>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>January 30, 2019</last_update_submitted>
  <last_update_submitted_qc>January 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2019</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>
  <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/NCT03823807
org study id: SHC013-II-01
nct id: NCT03823807
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of SH-1028 with
      Locally Advanced/Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with
      Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours
      harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene.
This is a multicenter, open-label, phase II study to evaluate the safety and efficacy of
      SH-1028 in locally advanced or metastatic NSCLC.The trail is divided into two parts:part A is
      dose extension phase,and Part B is expand sample size phase to confirm the efficacy of
      SH-1028.Patients must agree to provide a biopsy for central confirmation of T790M mutation
      status following confirmed disease progression on the most recent treatment regimen. The
      primary objective of the study is to assess the efficacy of SH-1028 by assessment of
      Objective Response Rate according to RECIST 1.1 by an Independent Central Review.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
time frame: From Baseline up to 30 days after the last dose, an average of 1 year.
measure: Maximum Plasma Concentration (Cmax）
time frame: Part A: Day 1 of Cycle 1 and 2 (21 days for 1 cycle).
measure: Area Under the Curve [AUC]
time frame: Part A: Day 1 of Cycle 1 and 2 (21 days for 1 cycle).
measure: Progression-free survival (PFS)
time frame: Every 2 cycles (21 days for 1 cycle) until end of follow-up, an average of 1 year.
measure: Duration of Response(DOR)
time frame: Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year.
measure: Disease Control Rates(DCR)
time frame: Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year.
measure: Overall survival(OS)
time frame: Every 2 cycles (21 days for 1 cycle) until end of treatment; Every 12 weeks until end of follow-up, an average of 2 years.
measure: Biomakers (eg. AF value of KRAS，MET mutation or other gene mutations ) of drug-resistance measured by next-generation sequencing (NGS).
time frame: at end of treatment，an average of 1 years.
description: optional，use NGS to analyse the gene associated with NSCLC and to determine the reason of SH-1028-resistance.
measure: Minimum Plasma Concentration (Cmin）
time frame: Before administration in Day 1 of cycle 2, 3 and 5 (21 days for 1 cycle).
arm group label: SH-1028
arm group type: Experimental
description: QD,Oral
intervention type: Drug
intervention name: SH-1028
description: Oral,100mg or 200mg ,QD, fasted
arm group label: SH-1028
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Caicun Zhou, MD
phone: +86-13301825532
email: caicunzhoudr@163.com
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No