<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/NCT04404543</url>
  </required_header>
  <id_info>
    <org_study_id>SYHA1807-CSP-001</org_study_id>
    <nct_id>NCT04404543</nct_id>
  </id_info>
  <brief_title>A Study of SYHA1807 in Subjects With Extensive-Stage Small Cell Lung Cancer</brief_title>
  <official_title>A Phase I, Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics and Clinical Activity of SYHA1807 Given Orally in Subjects With Extensive-Stage Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CSPC ZhongQi Pharmaceutical Technology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CSPC ZhongQi Pharmaceutical Technology 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 I, open-label, multi-center, non-randomized, 2-part first time inhuman (FTIH)&#xD;
      study for SYHA1807. Part 1 is a dose escalation phase to determine the recommended phase 2&#xD;
      dose (RP2D) for SYHA1807 based on the safety, tolerability and pharmacokinetics (PK) profiles&#xD;
      observed after oral administration of SYHA1807. The dose escalation study will be performed&#xD;
      according to the 3+3 design. Once RP2D is identified, an expansion cohort (Part 2) of up to&#xD;
      12~40 subjects will be enrolled to further evaluate the clinical activity and tolerability of&#xD;
      SYHA1807 in subjects with extensive-stage Small Cell Lung Cancer (SCLC).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 1, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</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:Number of Participants With Adverse Events</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1:Number of Participants With Serious Adverse Events (SAEs)</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/birth defect, other situations and is associated with liver injury or impaired liver function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1:Number of Participants With Dose Limiting Toxicities (DLT)</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>An event was considered a DLT if it occurs within the first 28 days of treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Dose Reduction or Delays</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Withdrawn Due to Toxicities</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. The number of participants with critical changes in values of vital signs in response to drug have been presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of SYHA1807</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of SYHA1807</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of SYHA1807</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. Tmax is the time to reach Cmax, determined directly from the concentration-time data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Phase Elimination Rate Constant (λz) Following Single and Repeat Dose Administration of SYHA1807</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of SYH1A1807</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Achieving Disease Control Rate at Week 6、12</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>Clinical response was assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate ,CR(Complete response)+PR(Partial response)+SD(Stable disease),based on RECIST version 1.1 at Week 6、12.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Value of NSE(Neurospecific enolase)、Pro-GRP(pro-gastrin releasing peptide)、CT (calcitonin) With Change From Baseline</measure>
    <time_frame>Through study completion, an average of 2 year</time_frame>
    <description>Analysis of the relationship between NSE(Neurospecific enolase)、Pro-GRP(pro-gastrin releasing peptide)、CT (calcitonin) NSE and anti-tumor activity.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">71</enrollment>
  <condition>Extensive-Stage Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Escalation Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Five dose levels will be tested according to the &quot;3 + 3&quot; dose-escalation design.&#xD;
The dose-limiting toxicity (DLT) will be assessed from the first administration of SYHA1807 to the end of the first cycle (28 days).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once the RP2D has been determined, an expansion cohort of up to 12~40 subjects will be enrolled in order to better characterize the clinical activity and safety profile of the RP2D.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SYHA1807</intervention_name>
    <description>Escalation Cohort Administration: Orally</description>
    <arm_group_label>Escalation Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SYHA1807</intervention_name>
    <description>Dose Expansion Cohort Administration: Orally</description>
    <arm_group_label>Dose Expansion Cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed diagnosis of advanced SCLC;&#xD;
&#xD;
          -  ECOG(Eastern Cooperative Oncology Group) performance status of 0 or 1;&#xD;
&#xD;
          -  Measurable disease according to RECIST v1.1;&#xD;
&#xD;
          -  Recovered from all toxicities associated with previous treatments;&#xD;
&#xD;
          -  Life expectancy ≥ 3 months;&#xD;
&#xD;
          -  Adequate organ function;&#xD;
&#xD;
          -  Use of reliable contraceptive methods;&#xD;
&#xD;
          -  Signed informed consent from the patient;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with primary malignant tumor other than small cell lung cancer;&#xD;
&#xD;
          -  Identified central nervous system metastasis (such as brain metastasis or meningeal&#xD;
             metastasis);&#xD;
&#xD;
          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated&#xD;
             drainage;&#xD;
&#xD;
          -  Inadequate washout period for previous anti-tumor therapy;&#xD;
&#xD;
          -  Previous treatment with any LSD1(lysine specific demethylase 1) inhibitor;&#xD;
&#xD;
          -  Unable to swallow oral medications;&#xD;
&#xD;
          -  History of serious systemic diseases;&#xD;
&#xD;
          -  History of serious autoimmune diseases；&#xD;
&#xD;
          -  HIV positive;&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kun Lou</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Medicine, CSPC Clinical Development Division</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kun Lou</last_name>
    <phone>031167808817</phone>
    <phone_ext>031167808817</phone_ext>
    <email>loukun@mail.ecspc.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xuefang Xia</last_name>
    <phone>031167808812</phone>
    <phone_ext>031167808812</phone_ext>
    <email>xiaxuefang@mail.ecspc.com</email>
  </overall_contact_backup>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 14, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>May 22, 2020</last_update_submitted>
  <last_update_submitted_qc>May 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 27, 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>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
  </condition_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/NCT04404543
org study id: SYHA1807-CSP-001
nct id: NCT04404543
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a phase I, open-label, multi-center, non-randomized, 2-part first time inhuman (FTIH)
      study for SYHA1807. Part 1 is a dose escalation phase to determine the recommended phase 2
      dose (RP2D) for SYHA1807 based on the safety, tolerability and pharmacokinetics (PK) profiles
      observed after oral administration of SYHA1807. The dose escalation study will be performed
      according to the 3+3 design. Once RP2D is identified, an expansion cohort (Part 2) of up to
      12~40 subjects will be enrolled to further evaluate the clinical activity and tolerability of
      SYHA1807 in subjects with extensive-stage Small Cell Lung Cancer (SCLC).
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part 1:Number of Participants With Adverse Events
time frame: Through study completion, an average of 2 year
description: An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
measure: Part 1:Number of Participants With Serious Adverse Events (SAEs)
time frame: Through study completion, an average of 2 year
description: SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/birth defect, other situations and is associated with liver injury or impaired liver function.
measure: Part 1:Number of Participants With Dose Limiting Toxicities (DLT)
time frame: Through study completion, an average of 2 year
description: An event was considered a DLT if it occurs within the first 28 days of treatment.
measure: Number of Participants With Dose Reduction or Delays
time frame: Through study completion, an average of 2 year
description: The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs.
measure: Number of Participants Withdrawn Due to Toxicities
time frame: Through study completion, an average of 2 year
description: Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.
measure: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline
time frame: Through study completion, an average of 2 year
description: Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented.
measure: Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug
time frame: Through study completion, an average of 2 year
description: Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. The number of participants with critical changes in values of vital signs in response to drug have been presented.
measure: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of SYHA1807
time frame: Through study completion, an average of 2 year
description: The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.
measure: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of SYHA1807
time frame: Through study completion, an average of 2 year
description: The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.
measure: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of SYHA1807
time frame: Through study completion, an average of 2 year
description: The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. Tmax is the time to reach Cmax, determined directly from the concentration-time data.
measure: Apparent Terminal Phase Elimination Rate Constant (λz) Following Single and Repeat Dose Administration of SYHA1807
time frame: Through study completion, an average of 2 year
description: The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.
measure: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of SYH1A1807
time frame: Through study completion, an average of 2 year
description: The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed.
measure: Number of Participants Achieving Disease Control Rate at Week 6、12
time frame: Through study completion, an average of 2 year
description: Clinical response was assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate ,CR(Complete response)+PR(Partial response)+SD(Stable disease),based on RECIST version 1.1 at Week 6、12.
measure: Value of NSE(Neurospecific enolase)、Pro-GRP(pro-gastrin releasing peptide)、CT (calcitonin) With Change From Baseline
time frame: Through study completion, an average of 2 year
description: Analysis of the relationship between NSE(Neurospecific enolase)、Pro-GRP(pro-gastrin releasing peptide)、CT (calcitonin) NSE and anti-tumor activity.
arm group label: Escalation Cohort
arm group type: Experimental
description: Five dose levels will be tested according to the "3 + 3" dose-escalation design.
The dose-limiting toxicity (DLT) will be assessed from the first administration of SYHA1807 to the end of the first cycle (28 days).
arm group label: Dose Expansion Cohort
arm group type: Experimental
description: Once the RP2D has been determined, an expansion cohort of up to 12~40 subjects will be enrolled in order to better characterize the clinical activity and safety profile of the RP2D.
intervention type: Drug
intervention name: SYHA1807
description: Escalation Cohort Administration: Orally
arm group label: Escalation Cohort
intervention type: Drug
intervention name: SYHA1807
description: Dose Expansion Cohort Administration: Orally
arm group label: Dose Expansion Cohort
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Kun Lou
role: Study Chair
affiliation: Department of Medicine, CSPC Clinical Development Division
last name: Kun Lou
phone: 031167808817
phone ext: 031167808817
email: loukun@mail.ecspc.com
last name: Xuefang Xia
phone: 031167808812
phone ext: 031167808812
email: xiaxuefang@mail.ecspc.com
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma