<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/NCT02977364</url>
  </required_header>
  <id_info>
    <org_study_id>HS-10241-101</org_study_id>
    <nct_id>NCT02977364</nct_id>
  </id_info>
  <brief_title>A Trial of C-met Kinase Inhibitor HS-10241 in Subjects With Advanced Solid Tumours</brief_title>
  <official_title>Phase I Trial to Investigate Safety and Tolerability Profile and Pharmacokinetics of C-met Kinase Inhibitor HS-10241 in Subjects With Advanced Solid Tumours</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Hansoh Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu Hansoh Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To investigate safety, tolerability and pharmacokinetics of C-met Kinase Inhibitor HS-10241&#xD;
      in Subjects With Advanced Solid Tumours that are not eligible for conventional or intensive&#xD;
      treatment. The dose of HS-10241 will be escalated to determine the dose limiting toxicity&#xD;
      (DLT) and the maximum tolerated dose (MTD) of HS-10241 in advanced cancer patients. At the&#xD;
      same time, pharmacokinetic characteristics and preliminary efficacy of HS-10241 will be&#xD;
      observed in advanced cancer patients. To determine the recommended dosage regimen for phase&#xD;
      II.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">November 2021</completion_date>
  <primary_completion_date type="Anticipated">November 2018</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>MTD of HS-10241 based on the incidence of dose limiting toxicities</measure>
    <time_frame>4 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Max concentration (Cmax) of HS-10241</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and intensity of Adverse Events according to Common Toxicity Criteria for AEs (CTCAE version 4.0)</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of HS-10241</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life(T1/2) of HS-10241</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Carcinoma</condition>
  <condition>Solid Tumor, Adult</condition>
  <arm_group>
    <arm_group_label>HS-10241 100mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HS-10241 100mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HS-10241 200mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HS-10241 200mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HS-10241 400mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HS-10241 400mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HS-10241 600mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HS-10241 600mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HS-10241 800mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HS-10241 800mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HS-10241 1000mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HS-10241 1000mg daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HS-10241</intervention_name>
    <arm_group_label>HS-10241 1000mg</arm_group_label>
    <arm_group_label>HS-10241 100mg</arm_group_label>
    <arm_group_label>HS-10241 200mg</arm_group_label>
    <arm_group_label>HS-10241 400mg</arm_group_label>
    <arm_group_label>HS-10241 600mg</arm_group_label>
    <arm_group_label>HS-10241 800mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed advanced or metastatic solid tumor for which standard therapy&#xD;
             does not exist, has failed, or has been refused.&#xD;
&#xD;
          2. c-MET positive patients preferred in dose escalation phase; c-MET of patients must&#xD;
             fulfill ICH++~+++ or FISH≥4 times in dose expansion phase.&#xD;
&#xD;
          3. Confirmed that there are at least 1 can be measured in accordance with the standard&#xD;
             RECIST1.1 by CT or MRI.&#xD;
&#xD;
          4. 18 ~65 years of age.&#xD;
&#xD;
          5. ECOG performance status of 0~1.&#xD;
&#xD;
          6. Life expectancy of at least 3 months.&#xD;
&#xD;
          7. Recovered from toxicities of prior anti-cancer treatment to Grade 1 or less (except&#xD;
             alopecia).&#xD;
&#xD;
          8. Acceptable hematologic status (without hematologic supports including hematopoietic&#xD;
             factor, blood transfusion) defined below:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500/μL&#xD;
&#xD;
               -  Platelet count ≥ 100000/μL&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
          9. Acceptable liver function defined below:&#xD;
&#xD;
               -  Total bilirubin ≤ 2 times upper limit of normal range (ULN)&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times&#xD;
                  ULN; however, ≤ 5 times ULN in a subject who has liver metastases&#xD;
&#xD;
         10. Acceptable renal function defined below:&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance (by the&#xD;
                  Cockcroft-Gault formula) ≥ 60 mL/minutes&#xD;
&#xD;
         11. Acceptable coagulation status defined below:&#xD;
&#xD;
               -  Prothrombin time &lt; 1.5 times ULN&#xD;
&#xD;
               -  Partial thrombin time &lt; 1.5 times UL&#xD;
&#xD;
         12. HIV Ag/Ab(-).&#xD;
&#xD;
         13. HCV Ab(-);or HCV Ab(+) but HCV RNA(-).&#xD;
&#xD;
         14. HBsAg（-）and HBcAb（-）in dose escalation phase；HBV DNA&lt;1×103copies/ml if HBsAg（+）or&#xD;
             HBcAb（+）in dose expansion phase.&#xD;
&#xD;
         15. Ability to understand the purposes and risks of the trial and his/her informed consent&#xD;
             using the human research ethics committee (HREC) approved informed consent form was&#xD;
             obtained before the entering the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Treatment with other c-MET TKI( specific target or multi-target)；&#xD;
&#xD;
          2. Anti-cancer treatment with radiation therapy（not including non target lesions&#xD;
             receiving palliative radiotherapy）, chemotherapy,hormonotherapy or surgery（small&#xD;
             surgery, including the implantation of external equipment or fine needle aspiration,&#xD;
             at least 7 days; diagnostic or palliative surgery, at least 14 days） within 4 weeks (6&#xD;
             weeks for nitrosoureas or Mitomycin C)prior to trial entry.&#xD;
&#xD;
          3. Medical history of difficulty swallowing, malabsorption or other chronic&#xD;
             gastrointestinal disease, or conditions that may hamper compliance and/or absorption&#xD;
             of the tested product&#xD;
&#xD;
          4. Cardiac disease with New York Heart Association (NYHA) Class III or IV, including&#xD;
             congestive heart failure, myocardial infarction within 6 months prior to the trial&#xD;
             entry, unstable arrhythmia, or symptomatic peripheral arterial vascular disease.&#xD;
&#xD;
          5. Symptomatic brain metastases or unstable brain metastases (notes: Patients with&#xD;
             asymptomatic brain metastases previously treated for the study, but must be kept&#xD;
             stable for at least 4 weeks and receive a stable dose of the drug)&#xD;
&#xD;
          6. Obvious neurological and mental disorder.&#xD;
&#xD;
          7. Other previous or concomitant tumors (except for the effective treatment of melanoma,&#xD;
             cervical carcinoma in situ, ductal carcinoma in situ or malignant tumor after&#xD;
             effective treatment, remission 3 years and considered to have been cured).&#xD;
&#xD;
          8. Active, uncontrolled bacterial, fungal infections, requiring systemic therapy.&#xD;
&#xD;
          9. Recent venous thrombosis (including deep vein thrombosis or pulmonary embolism within&#xD;
             0.5 year of trial entry)&#xD;
&#xD;
         10. History of organ allograft, autologous stem cell transplantation, or allogeneic stem&#xD;
             cell transplantation.&#xD;
&#xD;
         11. Participation in an investigational drug or device trial within 4 weeks prior to the&#xD;
             trial entry.&#xD;
&#xD;
         12. Anti-cancer treatment with radiation therapy, chemotherapy or immunotherapy within 4&#xD;
             weeks (6 weeks for nitrosoureas or Mitomycin C) prior to trial entry.&#xD;
&#xD;
         13. Major surgery, other than diagnostic surgery, within 4 weeks prior to the trial entry,&#xD;
             without complete recovery&#xD;
&#xD;
         14. Taking a medication that is a moderate or strong inhibitor or inducer of CYP2C9;&#xD;
             taking a medication that prolongs QT interval and has a risk of Torsades de Pointes .&#xD;
&#xD;
         15. Pregnant (positive serum beta human chorionic gonadotropin [β-HCG] test at Screening)&#xD;
             or is currently breast-feeding, their partner anticipates becoming&#xD;
             pregnant/impregnating during the trial or within 6 months after receiving the last&#xD;
             dose of trial treatment.&#xD;
&#xD;
         16. Known drug abuse or alcohol abuse.&#xD;
&#xD;
         17. Concomitant disease or condition that could interfere with the conduct of the trial,&#xD;
             or that would, in the opinion of the Investigator, pose an unacceptable risk to the&#xD;
             subject in this trial.&#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_contact>
    <last_name>Yuankai Shi, MD</last_name>
    <phone>86(10)87788293</phone>
    <email>syuankaipumc@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yuankai Shi, MD</last_name>
      <phone>86(10)87788293</phone>
      <email>syuankaipumc@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>November 27, 2016</last_update_submitted>
  <last_update_submitted_qc>November 27, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 30, 2016</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>Neoplasms</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/NCT02977364
org study id: HS-10241-101
nct id: NCT02977364
lead sponsor: 
has dmc: No
To investigate safety, tolerability and pharmacokinetics of C-met Kinase Inhibitor HS-10241
      in Subjects With Advanced Solid Tumours that are not eligible for conventional or intensive
      treatment. The dose of HS-10241 will be escalated to determine the dose limiting toxicity
      (DLT) and the maximum tolerated dose (MTD) of HS-10241 in advanced cancer patients. At the
      same time, pharmacokinetic characteristics and preliminary efficacy of HS-10241 will be
      observed in advanced cancer patients. To determine the recommended dosage regimen for phase
      II.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MTD of HS-10241 based on the incidence of dose limiting toxicities
time frame: 4 weeks
measure: Progression-free survival (PFS)
time frame: 12 months
measure: Max concentration (Cmax) of HS-10241
time frame: 4 weeks
measure: Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
time frame: 8 weeks
measure: Incidence and intensity of Adverse Events according to Common Toxicity Criteria for AEs (CTCAE version 4.0)
time frame: 8 weeks
measure: Area under the plasma concentration versus time curve (AUC) of HS-10241
time frame: 4 weeks
measure: Elimination half-life(T1/2) of HS-10241
time frame: 4 weeks
arm group label: HS-10241 100mg
arm group type: Experimental
description: HS-10241 100mg daily
arm group label: HS-10241 200mg
arm group type: Experimental
description: HS-10241 200mg daily
arm group label: HS-10241 400mg
arm group type: Experimental
description: HS-10241 400mg daily
arm group label: HS-10241 600mg
arm group type: Experimental
description: HS-10241 600mg daily
arm group label: HS-10241 800mg
arm group type: Experimental
description: HS-10241 800mg daily
arm group label: HS-10241 1000mg
arm group type: Experimental
description: HS-10241 1000mg daily
intervention type: Drug
intervention name: HS-10241
arm group label: HS-10241 1000mg
arm group label: HS-10241 100mg
arm group label: HS-10241 200mg
arm group label: HS-10241 400mg
arm group label: HS-10241 600mg
arm group label: HS-10241 800mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Yuankai Shi, MD
phone: 86(10)87788293
email: syuankaipumc@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No