<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/NCT04503902</url>
  </required_header>
  <id_info>
    <org_study_id>JS001D-C-102</org_study_id>
    <nct_id>NCT04503902</nct_id>
  </id_info>
  <brief_title>Toripalimab Combined With Donafenib in the Treatment of Advanced Hepatocellular Carcinoma</brief_title>
  <acronym>HCC</acronym>
  <official_title>A Multi-center, Open, Dose Exploration and Dose Expansion Phase I/II Clinical Study of Toripalimab（JS001） Combined With Donafenib in Patients With Advanced Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Suzhou Zelgen Biopharmaceuticals 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 study is an open, multi-center phase I/II clinical study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It will explore the tolerability (phase I) and effectiveness (phase II) of the Donafenib&#xD;
      tosilate tablets combined with Toripalimab injection in patients with advanced HCC. The study&#xD;
      is conducted in two phases, the first phase is the dose exploration phase (phase I), and the&#xD;
      second phase is the dose expansion phase (phase II).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 15, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Dose limiting toxicity (DLT)</measure>
    <time_frame>28 days after the first dose of JS001 and Donafenib</time_frame>
    <description>Severe toxicity that may be related to JS001 or donafenib during dose escalation of phase I clinical trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate（ORR） as determined by the Invertigator using RECIST V1.1</measure>
    <time_frame>From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months</time_frame>
    <description>The ratio of patients who are evaluated as CR or PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-JS001 antibody</measure>
    <time_frame>From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months</time_frame>
    <description>The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months</time_frame>
    <description>The Kaplan-Meier survival from the initiation date of first cycle until the date of first documented progression or date of death</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">46</enrollment>
  <condition>Advanced Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>JS001+Donafenib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Donafenib 100mg QD/100 mg BID/200 mg BID orally + JS001 240mg Q3W iv</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donafenib Tosilate Tablets</intervention_name>
    <description>In the dose exploration phase (phase I)，three doses of Donafenib tosylate tablets [100 mg once a day (QD); 100 mg twice a day (BID); 200 mg, BID] will be explored. In the dose expansion phase (phase II), patients will be treated at the recommended dose for phase 2(RP2D).The RP2D will be determined by the dose escalation study.</description>
    <arm_group_label>JS001+Donafenib</arm_group_label>
    <other_name>Donafenib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab Injection</intervention_name>
    <description>JS001 will be administrated by intravenous (i.v.) infusion once every 21 days</description>
    <arm_group_label>JS001+Donafenib</arm_group_label>
    <other_name>JS001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with locally advanced or metastatic HCC who are not suitable for surgical&#xD;
             resection, who are clinically diagnosed or confirmed by histopathology and/or cytology&#xD;
             according to the &quot;Standards for the Diagnosis and Treatment of Primary Liver Cancer&quot;&#xD;
             (2017);&#xD;
&#xD;
          -  At least one measurable lesion (according to RECIST v1.1);&#xD;
&#xD;
          -  ECOG performance status score of 0 or 1;&#xD;
&#xD;
          -  Life expectancy ≥ 12 weeks；&#xD;
&#xD;
          -  Have not received systemic therapy (systemic chemotherapy and/or molecular targeted&#xD;
             therapy).If the patient has received adjuvant chemotherapy after local treatment, the&#xD;
             chemotherapy needs to be over for more than 12 months, and disease progression or&#xD;
             metastasis occurs；&#xD;
&#xD;
          -  Fully understand this research and voluntarily sign the ICF。&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with diffuse liver cancer, hepatic encephalopathy that is difficult to&#xD;
             control, and liver cancer patients whose lesion size accounts for 70% or more of the&#xD;
             entire liver.&#xD;
&#xD;
          -  Patients with intrahepatic cholangiocarcinoma (ICC) or HCC-ICC mixed type；&#xD;
&#xD;
          -  Tumor invades inferior vena cava VP4.&#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>Shukui Qin, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>No.81 Hospital of PLA</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shukui Qin, PhD</last_name>
    <phone>+86-025-80864541</phone>
    <email>qinsk@csco.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>No.81 Hospital of PLA</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>215006</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shukui Qin</last_name>
      <phone>+86-025-80864541</phone>
      <email>qinsk@csco.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>November 28, 2022</last_update_submitted>
  <last_update_submitted_qc>November 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HCC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</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/NCT04503902
org study id: JS001D-C-102
nct id: NCT04503902
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is an open, multi-center phase I/II clinical study.
It will explore the tolerability (phase I) and effectiveness (phase II) of the Donafenib
      tosilate tablets combined with Toripalimab injection in patients with advanced HCC. The study
      is conducted in two phases, the first phase is the dose exploration phase (phase I), and the
      second phase is the dose expansion phase (phase II).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose limiting toxicity (DLT)
time frame: 28 days after the first dose of JS001 and Donafenib
description: Severe toxicity that may be related to JS001 or donafenib during dose escalation of phase I clinical trial
measure: Objective response rate（ORR） as determined by the Invertigator using RECIST V1.1
time frame: From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months
description: The ratio of patients who are evaluated as CR or PR
measure: Anti-JS001 antibody
time frame: From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months
measure: Overall survival (OS)
time frame: From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months
description: The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date.
measure: Progression free survival (PFS)
time frame: From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months
description: The Kaplan-Meier survival from the initiation date of first cycle until the date of first documented progression or date of death
arm group label: JS001+Donafenib
arm group type: Experimental
description: Donafenib 100mg QD/100 mg BID/200 mg BID orally + JS001 240mg Q3W iv
intervention type: Drug
intervention name: Donafenib Tosilate Tablets
description: In the dose exploration phase (phase I)，three doses of Donafenib tosylate tablets [100 mg once a day (QD); 100 mg twice a day (BID); 200 mg, BID] will be explored. In the dose expansion phase (phase II), patients will be treated at the recommended dose for phase 2(RP2D).The RP2D will be determined by the dose escalation study.
arm group label: JS001+Donafenib
other name: Donafenib
intervention type: Drug
intervention name: Toripalimab Injection
description: JS001 will be administrated by intravenous (i.v.) infusion once every 21 days
arm group label: JS001+Donafenib
other name: JS001
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Shukui Qin, PhD
role: Principal Investigator
affiliation: No.81 Hospital of PLA
last name: Shukui Qin, PhD
phone: +86-025-80864541
email: qinsk@csco.org.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
sharing ipd: No