<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/NCT04408079</url>
  </required_header>
  <id_info>
    <org_study_id>TQB3558-Ⅰ-01</org_study_id>
    <nct_id>NCT04408079</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3558 Tablets</brief_title>
  <official_title>A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3558 Tablets</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chia Tai Tianqing Pharmaceutical Group 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>
      This is a study to evaluate the maximum tolerated dose (MTD) , occurrence of all adverse&#xD;
      events (AE) and serious adverse events (SAE) , pharmacokinetic parameters and antitumor&#xD;
      effect of TQB3558 tablets in Chinese adult patients with advanced solid tumors .The study is&#xD;
      divided into phase Ia and phase Ib. Phase Ia: dose escalation period, to evaluate the safety&#xD;
      and tolerability of TQB3558 tablets, determine MTD; Phase Ib: effectiveness exploration&#xD;
      period, to expand the safe and effective dose group, recommend appropriate dosage and method&#xD;
      for subsequent clinical research.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 25, 2020</start_date>
  <completion_date type="Anticipated">October 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2022</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>Baseline up to 28 days</time_frame>
    <description>MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events (AE) and serious adverse events (SAE)</measure>
    <time_frame>Baseline up to 28 days</time_frame>
    <description>The occurrence of all adverse events (AE) and serious adverse events (SAE).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>up to 96 weeks</time_frame>
    <description>Percentage of participants achieving complete response (CR) and partial response (PR).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.</time_frame>
    <description>To characterize the pharmacokinetics of TQB3558 by assessment of time to reach maximum plasma concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.</time_frame>
    <description>Cmax is the maximum plasma concentration of TQB3558 or metabolite(s).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t</measure>
    <time_frame>15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.</time_frame>
    <description>To characterize the pharmacokinetics of TQB3558 by assessment of area under the plasma concentration time curve from zero to infinity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/f</measure>
    <time_frame>15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.</time_frame>
    <description>CL/f is total clearance rate for TQB3558.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate（DCR）</measure>
    <time_frame>up to 96 weeks</time_frame>
    <description>Percentage of participants achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>up to 96 weeks</time_frame>
    <description>PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>up to 96 weeks</time_frame>
    <description>DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <arm_group>
    <arm_group_label>TQB3558 Tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TQB3558 tablets administered orally once. Then TQB3558 tablet administered orally, once daily in 28-day cycle after 4 days of first administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TQB3558</intervention_name>
    <description>TQB3558 is a kinase inhibitor of the TRK protein family.</description>
    <arm_group_label>TQB3558 Tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Histologically or cytologically confirmed advanced malignant solid tumors, without&#xD;
             conventional treatment methods or fail or relapse after treatment.&#xD;
&#xD;
             2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Life&#xD;
             expectancy ≥12 weeks.&#xD;
&#xD;
             3. Has at least one measurable lesion (based on RECIST 1.1) or bone metastases. 4.&#xD;
             Adequate organ system function. 5. Patients need to adopt effective methods of&#xD;
             contraception. 6. Understood and signed an informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Has received TRK inhibitors. 2. Has participated in any other clinical trials, or&#xD;
             used other anti-cancer drugs, or received major surgical operations within 4 weeks&#xD;
             before first administration.&#xD;
&#xD;
             3. Has received local radiotherapy within 7 days or bone marrow radiotherapy within 4&#xD;
             weeks before the first administration.&#xD;
&#xD;
             4. Has other malignant tumors in 2 years, except for cured or locally curable cancers.&#xD;
&#xD;
             5. Has known spinal cord compression and cancerous meningitis. 6. Has interstitial&#xD;
             lung disease, drug-induced interstitial lung disease, history of radiation lung&#xD;
             disease requiring steroid therapy.&#xD;
&#xD;
             7. Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated&#xD;
             drainage.&#xD;
&#xD;
             8. Obvious cardiovascular diseases. 9. Has a history of autoimmune disease,&#xD;
             immunodeficiency. 10. Lactating women. 11. According to the judgement of the&#xD;
             researchers, there are other factors that subjects are not suitable for the study.&#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>Zan Shen, Doctor</last_name>
    <phone>021-24058431</phone>
    <email>Sshenzzan@vip.sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shanghai Sixth People's Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200233</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zan Shen, Doctor</last_name>
      <phone>021-24058431</phone>
      <email>Sshenzzan@vip.sina.com</email>
    </contact>
    <investigator>
      <last_name>Zan Shen, Doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>July 6, 2020</last_update_submitted>
  <last_update_submitted_qc>July 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04408079
org study id: TQB3558-Ⅰ-01
nct id: NCT04408079
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a study to evaluate the maximum tolerated dose (MTD) , occurrence of all adverse
      events (AE) and serious adverse events (SAE) , pharmacokinetic parameters and antitumor
      effect of TQB3558 tablets in Chinese adult patients with advanced solid tumors .The study is
      divided into phase Ia and phase Ib. Phase Ia: dose escalation period, to evaluate the safety
      and tolerability of TQB3558 tablets, determine MTD; Phase Ib: effectiveness exploration
      period, to expand the safe and effective dose group, recommend appropriate dosage and method
      for subsequent clinical research.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: Baseline up to 28 days
description: MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT.
measure: Adverse events (AE) and serious adverse events (SAE)
time frame: Baseline up to 28 days
description: The occurrence of all adverse events (AE) and serious adverse events (SAE).
measure: Overall response rate (ORR)
time frame: up to 96 weeks
description: Percentage of participants achieving complete response (CR) and partial response (PR).
measure: Tmax
time frame: 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
description: To characterize the pharmacokinetics of TQB3558 by assessment of time to reach maximum plasma concentration.
measure: Cmax
time frame: 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
description: Cmax is the maximum plasma concentration of TQB3558 or metabolite(s).
measure: AUC0-t
time frame: 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
description: To characterize the pharmacokinetics of TQB3558 by assessment of area under the plasma concentration time curve from zero to infinity.
measure: CL/f
time frame: 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11.
description: CL/f is total clearance rate for TQB3558.
measure: Disease control rate（DCR）
time frame: up to 96 weeks
description: Percentage of participants achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).
measure: Progression-free survival (PFS)
time frame: up to 96 weeks
description: PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
measure: Duration of Response (DOR)
time frame: up to 96 weeks
description: DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.
arm group label: TQB3558 Tablets
arm group type: Experimental
description: TQB3558 tablets administered orally once. Then TQB3558 tablet administered orally, once daily in 28-day cycle after 4 days of first administration.
intervention type: Drug
intervention name: TQB3558
description: TQB3558 is a kinase inhibitor of the TRK protein family.
arm group label: TQB3558 Tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zan Shen, Doctor
phone: 021-24058431
email: Sshenzzan@vip.sina.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor