<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/NCT03243643</url>
  </required_header>
  <id_info>
    <org_study_id>HS-10241-I-101</org_study_id>
    <nct_id>NCT03243643</nct_id>
  </id_info>
  <brief_title>Tolerability, Safety, Pharmacokinetics and Efficacy of HS-10241 Single Agent or Combined With Apatinib in Patients With Advanced Solid Tumors</brief_title>
  <acronym>HS:Hansoh;</acronym>
  <official_title>Tolerability, Safety, Pharmacokinetics and Efficacy of HS-10241 Single Agent or Combined With Apatinib in Patients With Advanced Solid Tumors</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To investigate tolerability, safety, pharmacokinetics and efficacy of C-met Kinase Inhibitor&#xD;
      HS-10241 single agent or combined with Apatinib in Subjects With Advanced Solid Tumours that&#xD;
      are not eligible for conventional or intensive treatment. The dose of HS-10241 will be&#xD;
      escalated to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD)&#xD;
      of HS-10241 single agent and in combination with Apatinib in advanced cancer patients. At the&#xD;
      same time, pharmacokinetic characteristics and preliminary efficacy of HS-10241 or combined&#xD;
      with Apatinb will be observed in advanced cancer patients. To determine the recommended&#xD;
      dosage regimen for phase II.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 8, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">July 2019</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicities (DLT)</measure>
    <time_frame>Day1 to day 38 (DLT observation period)</time_frame>
    <description>To assess MTD and DLT of HS-10241 single agent（D1-D17） then combined with aptatinib （D18-D38） in patients with advanced solid tumors.According to the &quot;3+3&quot; dose escalation design DLT will be determined.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Day1 to day 38 (DLT observation period)</time_frame>
    <description>One dose level below the dose level determined as DLT will be MTD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events and Serious Adverse Events</measure>
    <time_frame>From the day of ICF (Informed Consent Form) until 30 days after the last dose</time_frame>
    <description>To asess the safety of HS-10241 single agent the combined with apatinib in patients with advanced solid tumor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of maximum plasma concentration (Cmax)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>Including HS-10241 single dose （D1）/multiple dose of HS-10241（D17） and multiple dose of Apatinib（D38）.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of the area under the plasma concentration-time versus time curve(AUC)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>Area Under Curve(AUC0-t) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of the area under the plasma concentration-time versus time curve(AUC)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>AUC(0-inf) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of time of maximum plasma concentration (Tmax)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>Including HS-10241 single dose （D1）/multiple dose of HS-10241（D17） and multiple dose of apatinib（D38）.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of elimination half life (T1/2)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>T1/2 is measured after single dose administration of HS-10241 at day 1. T1/2 is measured after repeat once-daily dose administration of HS-10241 at day 17.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Measurement of mean retention time (MRT)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>MRT is measured after single dose administration of HS-10241 at day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of apparent volume of distribution (Vd)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>Vd is measured after single dose administration of HS-10241 at day 1. Vd is measured after repeated once-daily dose administration of HS-10241 at day 17.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of clearance (Cl)</measure>
    <time_frame>Day 1 to day 38</time_frame>
    <description>Vd is measured after single dose administration of HS-10241 at day 1. Vd is measured after repeated once-daily dose administration of HS-10241 at day 17.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response Rate</measure>
    <time_frame>Approximately 1 year</time_frame>
    <description>Determined using RECIST v1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>Approximately 1 year</time_frame>
    <description>Determined using RECIST v1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>Approximately 1 year</time_frame>
    <description>Determined using RECIST v1.1 criteria</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>HS-1024+apatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For part 1 (PK study) subjects will be given single dose of HS-10241 and then multiple dose of HS-10241 (1 cycle, each cycle 14days) and then HS-10241+aptatinib (each cycle 21 days) until PD.&#xD;
For part 2 (expansion study) subjects will be given HS-10241+aptatinib (each cycle 21 days) until PD (Progression of disease).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HS-10241</intervention_name>
    <description>HS-10241 is provided as white, film-coated,immediate release tablets containing HS-10241 at dosage strengths of 20mg/50mg/100 mg. Multiple tablets of HS-10241 will be administered daily to achieve targeted doses of HS-10241: 200 mg-1200 mg. Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal.</description>
    <arm_group_label>HS-1024+apatinib</arm_group_label>
    <other_name>c-met inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib is provided as white, film-coated,immediate release tablets containing aptinib at dosage strengths of 250mg. Apatinib will be administered daily to achieve targeted doses of 500 mg. Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal.</description>
    <arm_group_label>HS-1024+apatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18-75 years of age.&#xD;
&#xD;
          2. Histologically or cytologically confirmed advanced or metastatic solid tumor for which&#xD;
             standard therapy does not exist, has failed.；For part 2 (Expansion part) c-met&#xD;
             immunohistochemistry (IHC) positive（IHC++ or IHC+++）and with at least one measurable&#xD;
             disease according to RECIST 1.1.&#xD;
&#xD;
          3. No difficulty that may hamper compliance and/or absorption of the tested product&#xD;
             (swallowing difficulty, chronic gastrointestinal disease like diarrhea and intestinal&#xD;
             obstruction )&#xD;
&#xD;
          4. ECOG (Eastern Cooperative Oncology Group) performance status of 0～1.&#xD;
&#xD;
          5. Life expectancy of at least 3 months.&#xD;
&#xD;
          6. Adequate organ function:（No blood transfusion or hematopoietic stimulating factor&#xD;
             within 14days of screening stage）：&#xD;
&#xD;
          7. Acceptable hematologic status (without hematologic supports including hematopoietic&#xD;
             factor, blood transfusion) defined below:：Absolute neutrophil count (ANC) ≥1500/μL&#xD;
&#xD;
          8. Platelet count ≥90000/μL,，Hemoglobin ≥9.0 g/dL&#xD;
&#xD;
          9. Acceptable liver function defined below:：Total bilirubin ≤ 1.5 times upper limit of&#xD;
             normal range (ULN)&#xD;
&#xD;
         10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times ULN;&#xD;
             however, ≤5 times ULN in a subject who has liver metastases.&#xD;
&#xD;
         11. Acceptable renal function defined below:：Serum creatinine ≤1.5 times ULN or calculated&#xD;
             creatinine clearance (by the Cockcroft-Gault formula) ≥60 mL/minutes.&#xD;
&#xD;
         12. Acceptable cardiac function defined below:： left ventricular ejection&#xD;
             fraction，LVEF≥50% ；normal ECG，QTc male&lt;450ms，female&lt;470ms&#xD;
&#xD;
         13. Recovered from toxicities of prior anti-cancer treatment (NCI-CTCAE 4.03≤ grade 1,&#xD;
             except alopecia); Proper period of wash out of previous treatment (at least 5&#xD;
             half-life wash out), e.g. No nitrosoureas or mitomycin within 6 weeks，no cytotoxic&#xD;
             drugs, monoclonal antibodies, radiation therapy, or surgery within 4 weeks and no&#xD;
             endocrine therapy or tyrosine kinase inhibitors (TKIs) within 2 weeks before first&#xD;
             dose of the tested product.&#xD;
&#xD;
         14. Non-surgical sterilization or post-menopause female must agree to use effective means&#xD;
             of contraception (IUD , medication or condom ) during and 8 weeks after the clinical&#xD;
             trial.Human Chorionic Gonadotropin ( HCG ) serum test must be negative tested 7 days&#xD;
             before the first dose of tested product and not being in the lactation period. For&#xD;
             male subjects whose female partners have childbearing potential must be surgical&#xD;
             sterilization or agree to use effective means of contraception during and 120 days&#xD;
             after the clinical trial.&#xD;
&#xD;
         15. Tumor tissue sample available or agree to provide biopsies for testing.&#xD;
&#xD;
         16. Volunteer to participate in the clinical trial, understand the procedure of trial and&#xD;
             approved informed consent obtained before entering the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Failed in previous c-met or VEGFR inhibitor treatment;&#xD;
&#xD;
          2. Participation in other clinical trial or the last dose of the other trail was taken&#xD;
             within 4 weeks.&#xD;
&#xD;
          3. Other anti-cancer treatment might be received during the trial leading to pause of the&#xD;
             trial.&#xD;
&#xD;
          4. Tumor infiltration of the vessel, tumor cavity or necrosis with risk of hemorrhage.&#xD;
&#xD;
          5. Central nervous system (CNS) metastases or meningeal metastases or primary nervous&#xD;
             system tumor untreated by surgery or radiotherapy.&#xD;
&#xD;
          6. Patients with clinical symptoms of ascites or pleural effusion, need therapeutic&#xD;
             puncture and drainage.&#xD;
&#xD;
          7. Uncontrolled chronic systematic complications (such as chronic pulmonary , hepatic,&#xD;
             renal or cardiac diseases).&#xD;
&#xD;
          8. Grade II myocardial ischemia or myocardial infarction or uncontrolled arrhythmia.&#xD;
             Cardiac dysfunction with New York Heart Association (NYHA) Class III or IV.&#xD;
&#xD;
          9. Hypertension and unable to be controlled within normal level following treatment of&#xD;
             two anti-hypertension agents (systolic blood pressure ≥140 mmHg, diastolic blood&#xD;
             pressure ≥90 mmHg).&#xD;
&#xD;
         10. Urine protein≥ ++，or 24 hour urine protein≥1.0 g；&#xD;
&#xD;
         11. Patients with or previous with clinically significant hemorrhage within 3 months, with&#xD;
             hemorrhage risk or being in anticoagulant and fibrinolytic treatment like&#xD;
             gastrointestinal bleeding , hemorrhagic ulcers, baseline defecate occult blood&#xD;
             positive and above or vasculitis. Abnormal coagulant function such as&#xD;
             INR(international normalized ratio)&gt;1.5 or PT （Prothrombin Time）&gt;ULN+4 seconds）.&#xD;
&#xD;
         12. Arterial or venous thromboembolism events within 6 months，like cerebral vascular&#xD;
             accident (transient ischemic attack, cerebral hemorrhage or cerebral infarction) or&#xD;
             deep venous thrombosis and pulmonary embolism.&#xD;
&#xD;
         13. Active infection needed for treatment.&#xD;
&#xD;
         14. HIV,HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) positive（HBV：HBsAg positive with&#xD;
             hepatic function abnormality and HBV-DNA≧104 copy/mL，HCV：HCV-RNA positive with hepatic&#xD;
             function abnormality）needed for antivirus treatment（only for Part 1）.&#xD;
&#xD;
         15. History of mental or neurological disorders.&#xD;
&#xD;
         16. Psychiatric drug abuse history or addiction history&#xD;
&#xD;
         17. Unable to complete the trial or withdraw in the middle of the trial due to conditions&#xD;
             like psychological state, family relationship, social or geographical factors or with&#xD;
             concomitant treatment or abnormal laboratory examinations judging by the investigator.&#xD;
&#xD;
         18. Concomitant diseases ( uncontrolled hypertension , severe diabetes and thyroid disease&#xD;
             ) deemed by the investigator to be likely to interfere with the subjects safety or&#xD;
             leads to discontinuation from the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Yi Li, Ph.D</last_name>
    <phone>021-68868570</phone>
    <email>liuy@shhrp.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>West China Hospital, Sichuan University</name>
      <address>
        <city>Chendu</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Feng Bi, Ph.D</last_name>
      <phone>028-85423203</phone>
      <email>bifeng@medmail.com.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>September 6, 2017</last_update_submitted>
  <last_update_submitted_qc>September 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apatinib</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/NCT03243643
org study id: HS-10241-I-101
nct id: NCT03243643
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To investigate tolerability, safety, pharmacokinetics and efficacy of C-met Kinase Inhibitor
      HS-10241 single agent or combined with Apatinib 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 single agent and in combination with Apatinib in advanced cancer patients. At the
      same time, pharmacokinetic characteristics and preliminary efficacy of HS-10241 or combined
      with Apatinb will be observed in advanced cancer patients. To determine the recommended
      dosage regimen for phase II.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Dose Limiting Toxicities (DLT)
time frame: Day1 to day 38 (DLT observation period)
description: To assess MTD and DLT of HS-10241 single agent（D1-D17） then combined with aptatinib （D18-D38） in patients with advanced solid tumors.According to the "3+3" dose escalation design DLT will be determined.
measure: Maximum Tolerated Dose (MTD)
time frame: Day1 to day 38 (DLT observation period)
description: One dose level below the dose level determined as DLT will be MTD.
measure: Adverse events and Serious Adverse Events
time frame: From the day of ICF (Informed Consent Form) until 30 days after the last dose
description: To asess the safety of HS-10241 single agent the combined with apatinib in patients with advanced solid tumor.
measure: The measurement of maximum plasma concentration (Cmax)
time frame: Day 1 to day 38
description: Including HS-10241 single dose （D1）/multiple dose of HS-10241（D17） and multiple dose of Apatinib（D38）.
measure: The measurement of the area under the plasma concentration-time versus time curve(AUC)
time frame: Day 1 to day 38
description: Area Under Curve(AUC0-t) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38.
measure: The measurement of the area under the plasma concentration-time versus time curve(AUC)
time frame: Day 1 to day 38
description: AUC(0-inf) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38.
measure: The measurement of time of maximum plasma concentration (Tmax)
time frame: Day 1 to day 38
description: Including HS-10241 single dose （D1）/multiple dose of HS-10241（D17） and multiple dose of apatinib（D38）.
measure: The measurement of elimination half life (T1/2)
time frame: Day 1 to day 38
description: T1/2 is measured after single dose administration of HS-10241 at day 1. T1/2 is measured after repeat once-daily dose administration of HS-10241 at day 17.
measure: The Measurement of mean retention time (MRT)
time frame: Day 1 to day 38
description: MRT is measured after single dose administration of HS-10241 at day 1.
measure: The measurement of apparent volume of distribution (Vd)
time frame: Day 1 to day 38
description: Vd is measured after single dose administration of HS-10241 at day 1. Vd is measured after repeated once-daily dose administration of HS-10241 at day 17.
measure: The measurement of clearance (Cl)
time frame: Day 1 to day 38
description: Vd is measured after single dose administration of HS-10241 at day 1. Vd is measured after repeated once-daily dose administration of HS-10241 at day 17.
measure: Duration of Response Rate
time frame: Approximately 1 year
description: Determined using RECIST v1.1 criteria
measure: Progression-Free Survival
time frame: Approximately 1 year
description: Determined using RECIST v1.1 criteria
measure: Objective Response Rate
time frame: Approximately 1 year
description: Determined using RECIST v1.1 criteria
arm group label: HS-1024+apatinib
arm group type: Experimental
description: For part 1 (PK study) subjects will be given single dose of HS-10241 and then multiple dose of HS-10241 (1 cycle, each cycle 14days) and then HS-10241+aptatinib (each cycle 21 days) until PD.
For part 2 (expansion study) subjects will be given HS-10241+aptatinib (each cycle 21 days) until PD (Progression of disease).
intervention type: Drug
intervention name: HS-10241
description: HS-10241 is provided as white, film-coated,immediate release tablets containing HS-10241 at dosage strengths of 20mg/50mg/100 mg. Multiple tablets of HS-10241 will be administered daily to achieve targeted doses of HS-10241: 200 mg-1200 mg. Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal.
arm group label: HS-1024+apatinib
other name: c-met inhibitor
intervention type: Drug
intervention name: Apatinib
description: Apatinib is provided as white, film-coated,immediate release tablets containing aptinib at dosage strengths of 250mg. Apatinib will be administered daily to achieve targeted doses of 500 mg. Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal.
arm group label: HS-1024+apatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yi Li, Ph.D
phone: 021-68868570
email: liuy@shhrp.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Apatinib
sharing ipd: No