<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/NCT03261791</url>
  </required_header>
  <id_info>
    <org_study_id>APA- ZS-PVTT</org_study_id>
    <nct_id>NCT03261791</nct_id>
  </id_info>
  <brief_title>Adjuvant Therapy With Apatinib for HCC Patients With PVTT Who Underwent Radical Resection</brief_title>
  <official_title>A Exploratory Study of Apatinib Adjuvant Therapy for Hepatocellular Carcinoma With Portal Vein Invasion Who Underwent Radical Resection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Zhongshan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Zhongshan Hospital</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>
      In this phase 2 study, we aim to evaluate the effects and safety of adjuvant apatinib therapy&#xD;
      for the patients who underwent R0 resection for hepatocellular carcinoma with portal vein&#xD;
      tumor thrombus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Portal vein tumor thrombus (PVTT) is one of the characteristics of advanced stage for&#xD;
      patients with hepatocellular carcinoma (HCC). There's limited treatment choice for these&#xD;
      patients. Even for those who underwent curative resection (R0 resection), the recurrence rate&#xD;
      was extremely high. Apatinib is a highly selective VEGFR2 inhibitor and reduces the&#xD;
      angiogenesis of tumor efficiently, which had been proven effective in many solid tumors, is a&#xD;
      Chinese domestic TKI targeting vascular endothelial growth factor receptor. Phase 2 study of&#xD;
      apatinib for patients with advanced HCC had shown signals of clinical efficacy and modest&#xD;
      safety. In this study, we aim to evaluate the effects and safety of adjuvant apatinib therapy&#xD;
      for the patients who underwent R0 resection for HCC with PVTT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">April 20, 2020</completion_date>
  <primary_completion_date type="Anticipated">January 20, 2020</primary_completion_date>
  <phase>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>recurrence-free survival</measure>
    <time_frame>24 months</time_frame>
    <description>From the date of liver surgery to the date of diagnosis of tumor recurrence</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>24 months</time_frame>
    <description>From the date of liver surgery to the date of death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>safety: the potential side effects</measure>
    <time_frame>24 months</time_frame>
    <description>The potential side effects</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Carcinoma, Hepatocellular</condition>
  <arm_group>
    <arm_group_label>Apatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Apatinib mesylate tablets 500 mg po qd.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib mesylate tablets 500 mg po qd.</description>
    <arm_group_label>Apatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged from 18-70 years.&#xD;
&#xD;
          2. HCC diagnosis confirmed by pathological examination who did not receive anti-tumor&#xD;
             treatment (anti-tumor treatment including but not limited to: local ablation therapy,&#xD;
             TACE, radiation therapy, chemotherapy, targeted drug therapy, etc.)&#xD;
&#xD;
          3. Underwent radical resection for hepatocellular carcinoma with portal vein tumor&#xD;
             thrombus, as assessed by preoperative imaging or intraoperative findings, within 4&#xD;
             weeks&#xD;
&#xD;
          4. Child-Pugh class: A or B7&#xD;
&#xD;
          5. The ECOG: 0-1 points&#xD;
&#xD;
          6. The expected survival time ≥ 6 months.&#xD;
&#xD;
          7. Main organs function is normal including:&#xD;
&#xD;
               -  blood routine examination&#xD;
&#xD;
                    -  HB ≥ 90 g/L&#xD;
&#xD;
                    -  ANC ≥ 1.5×109 /L&#xD;
&#xD;
                    -  PLT ≥ 80×109/L&#xD;
&#xD;
               -  biochemical test&#xD;
&#xD;
                    -  ALB ≥ 29 g/L&#xD;
&#xD;
                    -  ALT&lt;3 ULN and AST&lt; 3 ULN&#xD;
&#xD;
                    -  TBIL ≤ 1.5 ULN&#xD;
&#xD;
                    -  Serum creatinine ≤ 1.5 ULN；&#xD;
&#xD;
          8. Women of childbearing age must have pregnancy tests (serum or urine) within 7 days&#xD;
             prior to admission, and the results are negative and are willing to use appropriate&#xD;
             methods of contraception at 8 weeks after the trial and at the end of the test. For&#xD;
             men, surgical sterilization should be applied, or consent to the appropriate method of&#xD;
             contraception 8 weeks after the trial and at the end of the trial;&#xD;
&#xD;
          9. subjects voluntarily joined the study, signed informed consent, good compliance, and&#xD;
             followed up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hepatic duct carcinoma、mixed cell carcinoma and fiberboard layer cell carcinoma which&#xD;
             have confirmed; Past (5 years) or current with other malignant tumor, except skin&#xD;
             basal cell carcinoma and cervical carcinoma in situ.&#xD;
&#xD;
          2. Patients with hypertension who are unable to fall within normal range by&#xD;
             antihypertensive medications (systolic pressure &gt; 140 mmHg, diastolic pressure &gt; 90&#xD;
             mmHg).&#xD;
&#xD;
          3. With the second level of myocardial ischemia or myocardial infarction, poor control of&#xD;
             the arrhythmia (including QTc interval = 450 ms, male female = 470 ms).&#xD;
&#xD;
          4. Factors that affect oral medication, such as inability to swallow, chronic diarrhea&#xD;
             and intestinal obstruction, which significantly affect the use and absorption of&#xD;
             drugs.&#xD;
&#xD;
          5. Ascites with clinical symptoms requires therapeutic peritoneal paracentesis or&#xD;
             drainage.&#xD;
&#xD;
          6. In the past 6 months, with the history of alimentary tract hemorrhage or definite&#xD;
             gastrointestinal bleeding tendency, such as: the risk of bleeding esophageal varices,&#xD;
             local active ulcerative lesions, fecal occult blood; For those with fecal occult blood&#xD;
             (+), gastroscopy is required.&#xD;
&#xD;
          7. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within&#xD;
             28 days before entry;&#xD;
&#xD;
          8. Postoperative complications were not relieved.&#xD;
&#xD;
          9. Abnormal coagulation function (INR &gt; 1.5 or prothrombin time (PT) &gt; ULN+4 seconds),&#xD;
             with bleeding tendency or undergoing thrombolysis or anticoagulant therapy;&#xD;
&#xD;
         10. Past and present pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis,&#xD;
             radiation pneumonitis, drug associated pneumonia, and severe lung function impairment;&#xD;
&#xD;
         11. Urine routine showed that urinary protein is more than + + or confirmed 24 hours urine&#xD;
             protein is more than 1.0 g;&#xD;
&#xD;
         12. Symptomatic metastasis of the central nervous system;&#xD;
&#xD;
         13. Pregnant or lactating women; fertile patients who are unwilling or unable to adopt&#xD;
             effective contraceptives;&#xD;
&#xD;
         14. Patient with mental illness or a history of psychotropic substance abuse;&#xD;
&#xD;
         15. HIV infection;&#xD;
&#xD;
         16. Before operation, AFP or PIVKA-2 increased, but not decreased to normal range;&#xD;
&#xD;
         17. HBV-DNA&gt;10^3 copys/ml；&#xD;
&#xD;
         18. Other conditions that the investigators considered that not unsuitable for inclusion.&#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>Hui-CHuan Sun, MD&amp;PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jia Fan, MD&amp;PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiao-Dong Zhu</last_name>
    <phone>+8602164037181</phone>
    <email>zhuxiaodong@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Zhongshan Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>20032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiao-Dong Zhu, MD&amp;PhD</last_name>
      <email>zhuxiaodong@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Zhang ZM, Lai EC, Zhang C, Yu HW, Liu Z, Wan BJ, Liu LM, Tian ZH, Deng H, Sun QH, Chen XP. The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus. Int J Surg. 2015 Aug;20:8-16. doi: 10.1016/j.ijsu.2015.05.009. Epub 2015 May 27.</citation>
    <PMID>26026424</PMID>
  </reference>
  <reference>
    <citation>Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RT, Shiina S, Cheng AL, Jia JD, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010 Mar 18;4(2):439-74. doi: 10.1007/s12072-010-9165-7.</citation>
    <PMID>20827404</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>August 24, 2017</last_update_submitted>
  <last_update_submitted_qc>August 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hepatocellular carcinoma</keyword>
  <keyword>apatinib</keyword>
  <keyword>portal vein invasion</keyword>
  <keyword>adjuvant therapy</keyword>
  <keyword>resection</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>
  <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/NCT03261791
org study id: APA- ZS-PVTT
nct id: NCT03261791
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this phase 2 study, we aim to evaluate the effects and safety of adjuvant apatinib therapy
      for the patients who underwent R0 resection for hepatocellular carcinoma with portal vein
      tumor thrombus.
Portal vein tumor thrombus (PVTT) is one of the characteristics of advanced stage for
      patients with hepatocellular carcinoma (HCC). There's limited treatment choice for these
      patients. Even for those who underwent curative resection (R0 resection), the recurrence rate
      was extremely high. Apatinib is a highly selective VEGFR2 inhibitor and reduces the
      angiogenesis of tumor efficiently, which had been proven effective in many solid tumors, is a
      Chinese domestic TKI targeting vascular endothelial growth factor receptor. Phase 2 study of
      apatinib for patients with advanced HCC had shown signals of clinical efficacy and modest
      safety. In this study, we aim to evaluate the effects and safety of adjuvant apatinib therapy
      for the patients who underwent R0 resection for HCC with PVTT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: recurrence-free survival
time frame: 24 months
description: From the date of liver surgery to the date of diagnosis of tumor recurrence
measure: overall survival
time frame: 24 months
description: From the date of liver surgery to the date of death
measure: safety: the potential side effects
time frame: 24 months
description: The potential side effects
arm group label: Apatinib
arm group type: Experimental
description: Apatinib mesylate tablets 500 mg po qd.
intervention type: Drug
intervention name: Apatinib
description: Apatinib mesylate tablets 500 mg po qd.
arm group label: Apatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Hui-CHuan Sun, MD&PhD
role: Principal Investigator
affiliation: Fudan University
last name: Jia Fan, MD&PhD
role: Principal Investigator
affiliation: Fudan University
last name: Xiao-Dong Zhu
phone: +8602164037181
email: zhuxiaodong@gmail.com
facility: 
status: Recruiting
contact: 
country: China
citation: Zhang ZM, Lai EC, Zhang C, Yu HW, Liu Z, Wan BJ, Liu LM, Tian ZH, Deng H, Sun QH, Chen XP. The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus. Int J Surg. 2015 Aug;20:8-16. doi: 10.1016/j.ijsu.2015.05.009. Epub 2015 May 27.
PMID: 26026424
citation: Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RT, Shiina S, Cheng AL, Jia JD, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010 Mar 18;4(2):439-74. doi: 10.1007/s12072-010-9165-7.
PMID: 20827404
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Apatinib
sharing ipd: No