<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/NCT02968485</url>
  </required_header>
  <id_info>
    <org_study_id>SHR7390-I-101-AST</org_study_id>
    <nct_id>NCT02968485</nct_id>
  </id_info>
  <brief_title>Phase I Study of SHR7390 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR7390 in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This aim of study to assess the safety and tolerability of SHR7390 and to define the maximum&#xD;
      tolerated dose (MTD) of SHR7390 in the patients with advanced solid tumors.&#xD;
&#xD;
      To evaluate the pharmacokinetics of SHR7390 in patients with advanced solid tumors.&#xD;
&#xD;
      To study the effects of food on the pharmacokinetic parameters of SHR7390. To assess the&#xD;
      antitumor activity of SHR7390 in patients with advanced solid tumors preliminarily and&#xD;
      recommend reasonable dosage regimen for the follow-up clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, dose escalation study of repeated doses of SHR7390 in the patients&#xD;
      with advanced solid tumors that have no targeted agent as standard of therapy.&#xD;
&#xD;
      A study cycle is defined as SHR7390 administered once daily orally for 28 days. Dose limiting&#xD;
      toxicities (DLT) will be assessed in the first cycle of treatment. the trial is dose&#xD;
      escalation and is designed by Accelerated Titration Designs during initial accelerated phase.&#xD;
      when the significant toxicity or DLT is observed in any course of treatment,the accelerated&#xD;
      titration trial terminates and subsequent cohort sizes and dose escalation are a conventional&#xD;
      design of 3+3 patients. If one adverse event （AE） meets dose limiting toxicity (DLT) criteria&#xD;
      at a given dose, 3 additional patients will be enrolled in this dose cohort. If 2 DLTs are&#xD;
      determined at a given dose level, this dose will be designated as the MTD.&#xD;
&#xD;
      Additional patients will be enrolled for PK evaluations at different dose levels based on&#xD;
      preliminary safety and tolerability. Multiple blood samples at designated time points will be&#xD;
      collected for PK evaluations.&#xD;
&#xD;
      The safety, tolerability and AEs will be closely monitored throughout the study duration. The&#xD;
      preliminary effectiveness and clinical benefits of SHR7390 will be evaluated as a single&#xD;
      agent.&#xD;
&#xD;
      The evaluation of the effects of a high-fat, high-calorie meal on the single-dose&#xD;
      pharmacokinetics (PK) of SHR7390.The design to assess food-effect is a randomized, balanced,&#xD;
      2-treatment(fed vs. fasted), separated by an adequate wash-out period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">July 2019</completion_date>
  <primary_completion_date type="Anticipated">April 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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Day 1 to 28 ( Cycle 1)</time_frame>
    <description>to assess safety and tolerability of SHR7390 with a maximum tolerated dose (MTD) of SHR7390 in patients with advanced solid tumors</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The measurement of maximum plasma concentration (Cmax)</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of the area under the plasma concentration-time versus time curve(AUC)</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of elimination half life (T1/2)</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of time of maximum plasma concentration (Tmax)</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Measurement of mean retention time (MRT)</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of apparent volume of distribution (Vd)</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of clearance (Cl)</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of linear Relationship</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The measurement of drug accumulation ratio</measure>
    <time_frame>Up to 2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of maximum plasma concentration (Cmax) in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of the area under the plasma concentration-time versus time curve(AUC) in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of elimination half life(T1/2) in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of time of maximum concentration (Tmax) in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of mean retention time (MRT) in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of apparent volume of distribution (Vd）in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of clearance (Cl) in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comparison of AUC 0-24h in the fed and fasted states</measure>
    <time_frame>2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The imaging data of the subjects will be evaluated at the ends of cycle 1 and cycle 2 by RECIST1.1 evaluation criteria separately.</measure>
    <time_frame>2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate objective (ORR) will be evaluated at the different dose levels</measure>
    <time_frame>2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR) will be evaluated at the different dose levels</measure>
    <time_frame>2 cycles(each cycle 28 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>SHR7390</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 subjects with advanced solid tumors were received single and then multiple oral doses of SHR7390(2 cycles,each cycle 28days).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR7390</intervention_name>
    <description>SHR7390 is provided as white, film-coated,immediate release tablets containing SHR7390 at dosage strengths of 0.125 mg and 0.5 mg. Multiple tablets of SHR7390 will be administered daily to achieve targeted doses of SHR7390: 0.25 mg-4 mg. Tablets will be orally administered with 240 ml water, once daily, 2 hours after a meal.</description>
    <arm_group_label>SHR7390</arm_group_label>
    <other_name>MEK inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        The study is open to all males and females who meet the following inclusion criteria at&#xD;
        screening and baseline to participate in the study.&#xD;
&#xD;
        To be included to participate in this study each patient must:&#xD;
&#xD;
          1. 18-70 years of age, both women and men;&#xD;
&#xD;
          2. invalid the standard treatment or non standard and effective treatment in patients&#xD;
             with advanced solid tumors diagnosed by pathology;&#xD;
&#xD;
          3. the Eastern Cooperative Oncology Group （ECOG） General status (performance status, PS)&#xD;
             of 0-1;&#xD;
&#xD;
          4. the expected lifetime ≥ 3 months;&#xD;
&#xD;
          5. organ function you must meet the following requirements:&#xD;
&#xD;
               -  Adequate bone marrow reserve: including neutrophil absolute count,platelets and&#xD;
                  hemoglobin;&#xD;
&#xD;
               -  Liver: serum albumin ≥ 3.0 g/dl; bilirubin, Alanine aminotransferase（ALT）and&#xD;
                  aspartate aminotransferase（AST）≤ 1.5 x upper limit of normal value (ULN),if there&#xD;
                  is liver metastasis, the ALT or AST&#xD;
&#xD;
                    -  5x upper limit of normal value (ULN);&#xD;
&#xD;
               -  Kidneys: creatinine clearance ≥ 50 mL/min (Cockcroft-Gault of the standard&#xD;
                  formula）；&#xD;
&#xD;
               -  Heart: left ventricular ejection fraction ≥ 50%; normal Electrocardiograph (ECG)&#xD;
                  and corrected QT interval（QTc）;&#xD;
&#xD;
          6. The damage of the patients caused by other treatments has been restored;&#xD;
&#xD;
          7. A agreement to use a highly effective, non-hormonal form of contraception is required&#xD;
             for women of childbearing potential and men with partners of childbearing potential,&#xD;
             who were not sterilized surgically, for duration of the study treatment and after the&#xD;
             last dose of study treatment; For female patients of child bearing potential,who was&#xD;
             not sterilized surgically,the serum human chorionic gonadotropin （HCG） pregnancy test&#xD;
             must be the negative&#xD;
&#xD;
          8. Written informed consent is provided by signing the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects who meet any of the criteria listed below will not be eligible for participation&#xD;
        in this study. A patient will not be eligible for study participation if:&#xD;
&#xD;
          1. Previous treatment with other protein kinase MEK inhibitors;&#xD;
&#xD;
          2. Use of other investigational anti-cancer drugs or the termination of the&#xD;
             investigational drugs within the last four weeks;&#xD;
&#xD;
          3. Currently or possibly receiving other cancer therapy during the study period;&#xD;
&#xD;
          4. Presence of a factor that influences the oral drug (such as inability to swallow) or&#xD;
             presence of active gastrointestinal disease or other conditions that will interfere&#xD;
             significantly with the absorption, distribution, metabolism, or excretion of drug;&#xD;
&#xD;
          5. History of retinal vascular occlusion （RVO） or central serous retinopathy;&#xD;
&#xD;
          6. Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk&#xD;
             factor for retinal vein thrombosis or central serous retinopathy;&#xD;
&#xD;
          7. Intraocular pressure&gt;21mmHg as measured by tonography or glaucoma;&#xD;
&#xD;
          8. Tumor metastases of central nervous system or leptomeningeal metastases. primary&#xD;
             malignancy of the central nervous system;&#xD;
&#xD;
          9. Evidence of severe or uncontrolled systemic diseases (e.g. unstable or uncompensated&#xD;
             respiratory, hepatic, renal or cardiac diseases);&#xD;
&#xD;
         10. History of acute coronary syndromes (including unstable angina);&#xD;
&#xD;
         11. Presence of arrhythmia, myocardial ischemia with drug intervention. III-IV stage heart&#xD;
             failure as defined by the New York Heart Association (NYHA) functional classification&#xD;
             system.&#xD;
&#xD;
         12. Medical treatment for an acute phase of infection;&#xD;
&#xD;
         13. hepatitis B virus（HBV) or hepatitis C virus (HCV) infection stage with abnormal liver&#xD;
             function;&#xD;
&#xD;
         14. History of immunodeficiency, or other acquired and congenital immunodeficiency&#xD;
             disease;&#xD;
&#xD;
         15. Psychological, familial, sociological or geographical conditions that do not permit&#xD;
             compliance with protocol;&#xD;
&#xD;
         16. Unwillingness or inability to follow the procedures outlined in the protocol;&#xD;
&#xD;
         17. Concurrent condition that in the investigator's opinion would jeopardize compliance&#xD;
             with the protocol;&#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>RuiHua Xu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cancer Center,Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>RuiHua Xu, MD, PhD</last_name>
    <phone>86-20-8734-3008</phone>
    <email>xurh@sysucc.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yi Liu, PhD</last_name>
    <phone>86-21-6045-3192</phone>
    <phone_ext>822</phone_ext>
    <email>liuy@shhrp.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Cancer Center,Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>RuiHua Xu, MD, PhD</last_name>
      <phone>86-20-87343008</phone>
      <email>xurh@sysucc.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>October 7, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>January 14, 2019</last_update_submitted>
  <last_update_submitted_qc>January 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>advanced solid tumor</keyword>
  <keyword>Protein Kinase MEK inhibitor (MEKi)</keyword>
  <keyword>Safety</keyword>
  <keyword>Pharmacokinetics</keyword>
  <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/NCT02968485
org study id: SHR7390-I-101-AST
nct id: NCT02968485
lead sponsor: 
has dmc: No
This aim of study to assess the safety and tolerability of SHR7390 and to define the maximum
      tolerated dose (MTD) of SHR7390 in the patients with advanced solid tumors.

      To evaluate the pharmacokinetics of SHR7390 in patients with advanced solid tumors.

      To study the effects of food on the pharmacokinetic parameters of SHR7390. To assess the
      antitumor activity of SHR7390 in patients with advanced solid tumors preliminarily and
      recommend reasonable dosage regimen for the follow-up clinical trial.
This is an open-label, dose escalation study of repeated doses of SHR7390 in the patients
      with advanced solid tumors that have no targeted agent as standard of therapy.

      A study cycle is defined as SHR7390 administered once daily orally for 28 days. Dose limiting
      toxicities (DLT) will be assessed in the first cycle of treatment. the trial is dose
      escalation and is designed by Accelerated Titration Designs during initial accelerated phase.
      when the significant toxicity or DLT is observed in any course of treatment,the accelerated
      titration trial terminates and subsequent cohort sizes and dose escalation are a conventional
      design of 3+3 patients. If one adverse event （AE） meets dose limiting toxicity (DLT) criteria
      at a given dose, 3 additional patients will be enrolled in this dose cohort. If 2 DLTs are
      determined at a given dose level, this dose will be designated as the MTD.

      Additional patients will be enrolled for PK evaluations at different dose levels based on
      preliminary safety and tolerability. Multiple blood samples at designated time points will be
      collected for PK evaluations.

      The safety, tolerability and AEs will be closely monitored throughout the study duration. The
      preliminary effectiveness and clinical benefits of SHR7390 will be evaluated as a single
      agent.

      The evaluation of the effects of a high-fat, high-calorie meal on the single-dose
      pharmacokinetics (PK) of SHR7390.The design to assess food-effect is a randomized, balanced,
      2-treatment(fed vs. fasted), separated by an adequate wash-out period.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: Day 1 to 28 ( Cycle 1)
description: to assess safety and tolerability of SHR7390 with a maximum tolerated dose (MTD) of SHR7390 in patients with advanced solid tumors
measure: The measurement of maximum plasma concentration (Cmax)
time frame: Up to 2 cycles(each cycle 28 days)
measure: The measurement of the area under the plasma concentration-time versus time curve(AUC)
time frame: Up to 2 cycles(each cycle 28 days)
measure: The measurement of elimination half life (T1/2)
time frame: Up to 2 cycles(each cycle 28 days)
measure: The measurement of time of maximum plasma concentration (Tmax)
time frame: Up to 2 cycles(each cycle 28 days)
measure: The Measurement of mean retention time (MRT)
time frame: Up to 2 cycles(each cycle 28 days)
measure: The measurement of apparent volume of distribution (Vd)
time frame: Up to 2 cycles(each cycle 28 days)
measure: The measurement of clearance (Cl)
time frame: Up to 2 cycles(each cycle 28 days)
measure: The measurement of linear Relationship
time frame: Up to 2 cycles(each cycle 28 days)
measure: The measurement of drug accumulation ratio
time frame: Up to 2 cycles(each cycle 28 days)
measure: The comparison of maximum plasma concentration (Cmax) in the fed and fasted states
time frame: 2 weeks
measure: The comparison of the area under the plasma concentration-time versus time curve(AUC) in the fed and fasted states
time frame: 2 weeks
measure: The comparison of elimination half life(T1/2) in the fed and fasted states
time frame: 2 weeks
measure: The comparison of time of maximum concentration (Tmax) in the fed and fasted states
time frame: 2 weeks
measure: The comparison of mean retention time (MRT) in the fed and fasted states
time frame: 2 weeks
measure: The comparison of apparent volume of distribution (Vd）in the fed and fasted states
time frame: 2 weeks
measure: The comparison of clearance (Cl) in the fed and fasted states
time frame: 2 weeks
measure: The comparison of AUC 0-24h in the fed and fasted states
time frame: 2 weeks
measure: The imaging data of the subjects will be evaluated at the ends of cycle 1 and cycle 2 by RECIST1.1 evaluation criteria separately.
time frame: 2 cycles(each cycle 28 days)
measure: Response rate objective (ORR) will be evaluated at the different dose levels
time frame: 2 cycles(each cycle 28 days)
measure: Disease control rate (DCR) will be evaluated at the different dose levels
time frame: 2 cycles(each cycle 28 days)
arm group label: SHR7390
arm group type: Experimental
description: 60 subjects with advanced solid tumors were received single and then multiple oral doses of SHR7390(2 cycles,each cycle 28days).
intervention type: Drug
intervention name: SHR7390
description: SHR7390 is provided as white, film-coated,immediate release tablets containing SHR7390 at dosage strengths of 0.125 mg and 0.5 mg. Multiple tablets of SHR7390 will be administered daily to achieve targeted doses of SHR7390: 0.25 mg-4 mg. Tablets will be orally administered with 240 ml water, once daily, 2 hours after a meal.
arm group label: SHR7390
other name: MEK inhibitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: RuiHua Xu, MD, PhD
role: Principal Investigator
affiliation: The Cancer Center,Sun Yat-sen University
last name: RuiHua Xu, MD, PhD
phone: 86-20-8734-3008
email: xurh@sysucc.org.cn
last name: Yi Liu, PhD
phone: 86-21-6045-3192
phone ext: 822
email: liuy@shhrp.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No