xml: <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/NCT06041490</url>
    </required_header>
    <id_info>
      <org_study_id>K4001</org_study_id>
      <nct_id>NCT06041490</nct_id>
    </id_info>
    <brief_title>Adjuvant Therapy for High-risk Hepatocellular Carcinoma Post Liver Transplantation</brief_title>
    <official_title>A Randomized, Controlled, Open-label, Multi-center Clinical Trial of Multi-kinase Inhibitor Combined With Bevacizumab as Adjuvant Therapy in Patients With Hepatocellular Carcinoma and High-risk Recurrence Factors After Liver Transplantation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking Union Medical College Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking Union Medical College 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>
        1. Explore the impact of postoperative administration of multi-kinase inhibitors (including&#xD;
             sorafenib, lenvatinib, and regorafenib) in conjunction with bevacizumab on&#xD;
             post-transplant recurrence, overall survival, and drug safety in liver transplant&#xD;
             recipients at high risk of recurrence in hepatocellular carcinoma.&#xD;
  &#xD;
          2. The primary objective of this study is to evaluate the efficacy of multi-kinase&#xD;
             inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant&#xD;
             recipients with hepatocellular carcinoma who present high-risk factors for recurrence,&#xD;
             based on the one-year recurrence-free survival rate (1-year RFS rate).&#xD;
  &#xD;
          3. The secondary objectives of this study are to assess the effectiveness and safety of&#xD;
             multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver&#xD;
             transplant recipients with hepatocellular carcinoma who present high-risk factors for&#xD;
             recurrence, based on the following parameters: Recurrence-free survival (RFS) duration,&#xD;
             Overall survival (OS), Two-year and three-year RFS rates, Graft survival, Quality of&#xD;
             life evaluation (QoL), Incidence of adverse events and serious adverse events.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        To investigate the effect of multikinase inhibitors (including sorafenib, lenvatinib and&#xD;
        donafinib) combined with bevacizumab on recurrence, survival and safety in patients with&#xD;
        hepatocellular carcinoma (HCC) at high risk of recurrence after liver transplantation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">January 2027</completion_date>
    <primary_completion_date type="Anticipated">June 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>EFFICACY: One-year recurrence-free survival rate (1-year RFS rate)</measure>
      <time_frame>Baseline up to 12 months</time_frame>
      <description>One-year recurrence-free survival rate (1-year RFS rate): The one-year recurrence-free survival rate represents the proportion of patients, within a specified study population, who remain free from disease recurrence for at least one year following a designated treatment or intervention.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>EFFICACY: Recurrence-free survival (RFS) duration</measure>
      <time_frame>Baseline up to approximately 12 months</time_frame>
      <description>Recurrence-free survival (RFS) duration: From randomization to the time of disease recurrence evidence or any cause-induced mortality.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EFFICACY: Overall survival (OS)</measure>
      <time_frame>Baseline up to approximately 3 years</time_frame>
      <description>Overall survival (OS): The duration from randomization to mortality caused by any underlying factors serves as a crucial metric for evaluating the impact of interventions on study participants.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EFFICACY: Two-year and three-year RFS rates</measure>
      <time_frame>Baseline up to approximately 2-3 years</time_frame>
      <description>Two-year and three-year RFS rates: The two-year and three-year RFS rate represents the proportion of patients, within a specified study population, who remain free from disease recurrence for at least two or three year following a designated treatment or intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EFFICACY and SAFETY: Graft survival</measure>
      <time_frame>Baseline up to approximately 3 years</time_frame>
      <description>Graft survival: The interval between the commencement of randomization and the occurrence of graft loss is a pivotal time frame in transplantation research. In cases where patients are unaware of graft loss or when graft loss is not documented upon patient demise without confirmed graft loss, the time of graft loss is retrospectively evaluated using either the date of the last documented contact or the date of death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>QUALITY OF LIFE：Quality of life evaluation</measure>
      <time_frame>Baseline up to approximately 3 years</time_frame>
      <description>Quality of life evaluation (QoL) according by FACT-Hep.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>SAFETY: Incidence of adverse events and serious adverse events</measure>
      <time_frame>Baseline up to approximately 3 years</time_frame>
      <description>Incidence of adverse events and serious adverse events. Grade by CTCAE 5.0.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">88</enrollment>
    <condition>Liver Transplant; Complications</condition>
    <condition>Hepatocarcinoma</condition>
    <condition>Recurrent Osteosarcoma</condition>
    <condition>High-Risk Cancer</condition>
    <arm_group>
      <arm_group_label>multi-kinase inhibitors in combination with bevacizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>TKI (Sorafenib 400mg, bid, po or Lenvatinib 8mg, qd, po if bodyweight less than 60 kg,12mg, qd, po if bodyweight more than 60kg or Donafenib：200mg, bid, po) + bevacizumab：7.5mg/kg, infusion, Q3w</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Without adjuvant therapy</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>No intervention.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>multi-kinase inhibitors in combination with bevacizumab</intervention_name>
      <description>The eligible participants will start taking multi-kinase inhibitors between 4-8 weeks after liver transplantation. The choice of the specific multi-kinase inhibitor, including sorafenib, lenvatinib, or regorafenib, will be determined by the researchers based on factors such as the participant's tumor characteristics, liver function, physical condition, risk of side effects, economic status, and personal preference. The specific dosage and administration details can be found in the table provided. The maximum duration of multi-kinase inhibitor treatment will be 12 months or until any of the following conditions occur, whichever comes first: 1) The participant experiences intolerable toxic reactions that do not alleviate with dose adjustments, or 2) The participant has documented disease recurrence confirmed through imaging or withdraws from the study for other reasons.</description>
      <arm_group_label>multi-kinase inhibitors in combination with bevacizumab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Voluntary enrollment, accompanied by the signing of a written informed consent form,&#xD;
               is a prerequisite for participation in this study. This ensures that participants&#xD;
               enter the study based on their own decision and understanding of the research&#xD;
               objectives, procedures, and potential risks.&#xD;
  &#xD;
            2. The study includes individuals aged between 18 and 75 years, inclusive, without any&#xD;
               gender restrictions. This broad age range and gender inclusivity allow for a diverse&#xD;
               representation of participants, facilitating a comprehensive understanding of the&#xD;
               study outcomes across different demographic profiles.&#xD;
  &#xD;
            3. Prior to enrollment, participants must have undergone liver transplantation within the&#xD;
               preceding 4 to 8 weeks. This specific time frame serves as an inclusion criterion to&#xD;
               ensure that participants have recently undergone the surgical procedure, enabling&#xD;
               researchers to investigate the effects of the transplantation within a relevant&#xD;
               timeframe.&#xD;
  &#xD;
            4. Participants must have a confirmed pathological diagnosis of hepatocellular carcinoma&#xD;
               (HCC) and meet at least one of the following criteria:&#xD;
  &#xD;
               a) Pre-operative imaging or post-operative pathological confirmation of exceeding the&#xD;
               Milan criteria.&#xD;
  &#xD;
               b) Presence of major vascular invasion. c) Post-operative pathological confirmation of&#xD;
               the presence of microvascular invasion (MVI).&#xD;
  &#xD;
               d) Pre-operative imaging or post-operative pathological confirmation of the presence&#xD;
               of satellite nodules.&#xD;
  &#xD;
               e) Recurrence of HCC after liver resection and subsequent liver transplantation.&#xD;
  &#xD;
            5. Participants should have an anticipated life expectancy of more than 3 months.&#xD;
  &#xD;
            6. Participants should not have received systemic anti-tumor treatment prior to liver&#xD;
               transplantation, with the exception of pre-operative transarterial chemoembolization&#xD;
               (TACE), traditional Chinese medicine, and interferon treatment.&#xD;
  &#xD;
            7. Participants should have an Eastern Cooperative Oncology Group (ECOG) performance&#xD;
               status score of 0 to 1, indicating good functional status.&#xD;
  &#xD;
            8. Participants' liver function, as assessed by the Child-Pugh score, should be&#xD;
               classified as Grade A, indicating well-preserved liver function.&#xD;
  &#xD;
            9. HBsAg-positive patients should receive continuous antiviral therapy&#xD;
               post-transplantation, using first-line antiviral drugs such as entecavir, tenofovir,&#xD;
               or tenofovir alafenamide.&#xD;
  &#xD;
           10. Participants should have adequate hematological and organ function, based on the&#xD;
               laboratory test results obtained within 14 days before the initiation of the study&#xD;
               treatment, as follows:&#xD;
  &#xD;
               Laboratory tests (unless otherwise specified, no blood transfusion or use of G-CSF&#xD;
               within 14 days prior to screening):&#xD;
  &#xD;
                 1. Hemoglobin ≥ 90 g/L.&#xD;
  &#xD;
                 2. White blood cell count ≥ 3.0 x 10^9/L.&#xD;
  &#xD;
                 3. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.&#xD;
  &#xD;
                 4. Platelet count ≥ 75 x 10^9/L.&#xD;
  &#xD;
                    Biochemical tests (no use of albumin within 14 days prior to screening):&#xD;
  &#xD;
                 5. Serum albumin ≥ 28 g/L.&#xD;
  &#xD;
                 6. Total bilirubin ≤ 2 times the upper limit of normal (ULN).&#xD;
  &#xD;
                 7. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times&#xD;
                    ULN.&#xD;
  &#xD;
                 8. Alkaline phosphatase (ALP) ≤ 5 times ULN.&#xD;
  &#xD;
                 9. Creatinine ≤ 1.5 times ULN or creatinine clearance (CrCl) &gt; 50 mL/min (calculated&#xD;
                    using the standard Cockcroft-Gault formula):&#xD;
  &#xD;
                    - For females: CrCl = ((140 - age) x body weight (kg) x 0.85) / (72 x serum&#xD;
                    creatinine [mg/dL]).&#xD;
  &#xD;
                      -  For males: CrCl = ((140 - age) x body weight (kg) x 1.00) / (72 x serum&#xD;
                         creatinine [mg/dL]).&#xD;
  &#xD;
                    Coagulation Function:&#xD;
  &#xD;
                10. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times the&#xD;
                    Upper Limit of Normal (ULN) or PT prolongation ≤ 6 seconds.&#xD;
  &#xD;
                11. Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN.&#xD;
  &#xD;
           11. Women of Childbearing Potential: Women who agree to abstain from heterosexual&#xD;
               intercourse during the treatment period and for at least 6 months after the last dose&#xD;
               of the study drug, or use a contraceptive method with a failure rate of less than 1%&#xD;
               per year. For women who have experienced menstrual bleeding and have not reached a&#xD;
               postmenopausal state (continuous absence of menstruation for ≥12 months without any&#xD;
               other known cause) and have not undergone sterilization procedures (removal of ovaries&#xD;
               and/or uterus), they are considered to be of childbearing potential.&#xD;
  &#xD;
                 1. Examples of contraceptive methods with a failure rate of less than 1% per year&#xD;
                    include bilateral tubal ligation, male sterilization, hormone-based&#xD;
                    contraceptives that inhibit ovulation, hormone-releasing intrauterine devices,&#xD;
                    and copper intrauterine devices.&#xD;
  &#xD;
                 2. The reliability of sexual abstinence should be evaluated in relation to the&#xD;
                    duration of the clinical trial, patients' preferred lifestyle, and daily&#xD;
                    activities. Periodic abstinence methods (such as calendar-based methods,&#xD;
                    ovulation period methods, symptothermal methods, or post-ovulation methods) and&#xD;
                    withdrawal are not acceptable contraceptive methods.&#xD;
  &#xD;
           12. Men: Men who agree to abstain from heterosexual intercourse or use contraception and&#xD;
               also agree not to donate sperm, as defined below:&#xD;
  &#xD;
                 1. If the female partner is of childbearing potential, male patients must abstain&#xD;
                    from heterosexual intercourse during the treatment period and for 6 months after&#xD;
                    the last dose of the study drug or use a condom plus another contraceptive method&#xD;
                    to achieve a contraceptive failure rate of &lt;1% per year. During the same period,&#xD;
                    male patients must also agree not to donate sperm. If the female partner is&#xD;
                    already pregnant, male patients must abstain from heterosexual intercourse or use&#xD;
                    a condom for contraception during the treatment period and for 6 months after the&#xD;
                    last dose of the study drug to avoid potential effects on the fetus.&#xD;
  &#xD;
                 2. The reliability of sexual abstinence should be evaluated in relation to the&#xD;
                    duration of the clinical trial, patients' preferred lifestyle, and daily&#xD;
                    activities. Periodic abstinence methods (such as calendar-based methods,&#xD;
                    ovulation period methods, symptothermal methods, or post-ovulation methods) and&#xD;
                    withdrawal are not acceptable contraceptive methods.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          According to the information provided, the following patients are not eligible for&#xD;
          participation in this study.&#xD;
  &#xD;
            1. Patients with a previous histological/cytological diagnosis of fibrolamellar&#xD;
               hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or&#xD;
               other similar components.&#xD;
  &#xD;
            2. Patients with a history of malignancies other than hepatocellular carcinoma, unless&#xD;
               they meet the following criteria:&#xD;
  &#xD;
                 1. Patients who have undergone potentially curative treatment and have no evidence&#xD;
                    of the disease within the past 5 years.&#xD;
  &#xD;
                 2. Patients who have successfully undergone resection of basal cell carcinoma,&#xD;
                    squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ,&#xD;
                    or other in situ carcinomas; or patients who have been treated for superficial&#xD;
                    bladder cancer, have undergone surgical treatment, and have prostate-specific&#xD;
                    antigen (PSA) tumor markers within the normal range.&#xD;
  &#xD;
            3. Patients who are concurrently taking medications that may prolong the QTc interval&#xD;
               and/or induce torsades de pointes (Tdp) or medications that affect drug metabolism.&#xD;
  &#xD;
               Patients with a known or suspected history of allergies to sorafenib, lenvatinib,&#xD;
               donafenib, or similar drugs.&#xD;
  &#xD;
            4. Patients with active bleeding or coagulation abnormalities, bleeding tendencies, or&#xD;
               those undergoing thrombolysis, anticoagulant therapy, or antiplatelet therapy.&#xD;
  &#xD;
            5. Patients who have experienced thrombosis or thromboembolic events within the past 6&#xD;
               months, such as stroke and/or transient ischemic attack, deep vein thrombosis,&#xD;
               pulmonary embolism, etc.&#xD;
  &#xD;
          7.Patients who have experienced esophageal or gastric variceal bleeding due to portal&#xD;
          hypertension within the past 6 months or any life-threatening bleeding event within the&#xD;
          past 3 months. Patients with a history of gastrointestinal bleeding within the past 6&#xD;
          months or clear evidence of gastrointestinal bleeding tendencies, such as high-risk&#xD;
          esophageal varices, locally active gastrointestinal ulcers, fecal occult blood ≥(++), are&#xD;
          not eligible for inclusion. If fecal occult blood is (+), a gastroscopy examination is&#xD;
          required. Evidence or history of bleeding mechanism disorders with ≥3 grade (CTC-AE 5.0)&#xD;
          bleeding events, etc.&#xD;
  &#xD;
          8.Patients with clinically significant cardiovascular diseases, including but not limited&#xD;
          to acute myocardial infarction within the past 6 months, severe/unstable angina or coronary&#xD;
          artery bypass grafting, congestive heart failure (NYHA class &gt;2), poorly controlled or&#xD;
          requiring pacemaker therapy for arrhythmias, poorly controlled hypertension (systolic blood&#xD;
          pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) despite medication.&#xD;
  &#xD;
          9.Other significant clinical and laboratory abnormalities that the investigator deems to&#xD;
          impact safety assessment, such as uncontrolled diabetes, chronic kidney disease, peripheral&#xD;
          neuropathy of grade II or higher (CTCAE V5.0), thyroid dysfunction, etc.&#xD;
  &#xD;
          10.Active or poorly controlled severe infections, including:&#xD;
  &#xD;
            1. HIV-positive (HIV1/2 antibody).&#xD;
  &#xD;
            2. Active hepatitis B (positive for HBsAg or HBV DNA&gt;2000 IU/ml and abnormal liver&#xD;
               function).&#xD;
  &#xD;
            3. Active hepatitis C (positive for HCV antibody or HCV RNA≥103 copies/ml and abnormal&#xD;
               liver function).&#xD;
  &#xD;
            4. Active tuberculosis.&#xD;
  &#xD;
            5. Other uncontrolled active infections (CTCAE V5.0 &gt;2 grade). 11.Patients who have not&#xD;
               yet recovered from surgery, with unhealed wounds or severe postoperative&#xD;
               complications.&#xD;
  &#xD;
               12.Patients with substance abuse or any medical, psychological, or social conditions&#xD;
               that may affect the study, patient compliance, or potentially endanger patient safety.&#xD;
  &#xD;
               13.Patients who have received treatment with potent CYP3A4 inhibitors (such as&#xD;
               clarithromycin, indinavir, ketoconazole, lopinavir, nefazodone, nelfinavir, ritonavir,&#xD;
               saquinavir, telaprevir, voriconazole, etc.) within 7 days prior to study participation&#xD;
               or potent CYP3A4 inducers (such as phenytoin, phenobarbital, primidone, carbamazepine,&#xD;
               rifampin, rifabutin, rifapentine, St. John's wort, etc.) within 12 days prior to study&#xD;
               participation.&#xD;
  &#xD;
               14.Recipients of multiorgan transplantation. 15.Development of distant metastasis&#xD;
               within 1 month after transplantation. 16.Participation in another clinical trial&#xD;
               within the past 30 days. 17.Incomplete treatment duration of less than 3 months.&#xD;
               18.The investigator's comprehensive judgment deems the patient unsuitable for&#xD;
               participation in this 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_official>
      <last_name>haitao zhao</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>haitao zhao</last_name>
      <phone>01069156874</phone>
      <email>zhaoht@pumch.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Chinese Academy of Medical Sciences &amp; Peking Union Medical College Hospital (CAMS&amp;PUMCH)</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100730</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Haitao Zhao, Professor</last_name>
        <phone>+861069156042</phone>
        <email>zhaoht@pumch.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Hepatocarcinoma</keyword>
    <keyword>Liver Transplant</keyword>
    <keyword>Recurrence</keyword>
    <keyword>High-Risk</keyword>
    <keyword>multikinase inhibitor</keyword>
    <keyword>bevacizumab</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Hepatocellular</mesh_term>
      <mesh_term>Osteosarcoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Bevacizumab</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06041490
  org study id: K4001
  nct id: NCT06041490
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  1. Explore the impact of postoperative administration of multi-kinase inhibitors (including
             sorafenib, lenvatinib, and regorafenib) in conjunction with bevacizumab on
             post-transplant recurrence, overall survival, and drug safety in liver transplant
             recipients at high risk of recurrence in hepatocellular carcinoma.
  
          2. The primary objective of this study is to evaluate the efficacy of multi-kinase
             inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant
             recipients with hepatocellular carcinoma who present high-risk factors for recurrence,
             based on the one-year recurrence-free survival rate (1-year RFS rate).
  
          3. The secondary objectives of this study are to assess the effectiveness and safety of
             multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver
             transplant recipients with hepatocellular carcinoma who present high-risk factors for
             recurrence, based on the following parameters: Recurrence-free survival (RFS) duration,
             Overall survival (OS), Two-year and three-year RFS rates, Graft survival, Quality of
             life evaluation (QoL), Incidence of adverse events and serious adverse events.
  To investigate the effect of multikinase inhibitors (including sorafenib, lenvatinib and
        donafinib) combined with bevacizumab on recurrence, survival and safety in patients with
        hepatocellular carcinoma (HCC) at high risk of recurrence after liver transplantation.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: EFFICACY: One-year recurrence-free survival rate (1-year RFS rate)
  time frame: Baseline up to 12 months
  description: One-year recurrence-free survival rate (1-year RFS rate): The one-year recurrence-free survival rate represents the proportion of patients, within a specified study population, who remain free from disease recurrence for at least one year following a designated treatment or intervention.
  measure: EFFICACY: Recurrence-free survival (RFS) duration
  time frame: Baseline up to approximately 12 months
  description: Recurrence-free survival (RFS) duration: From randomization to the time of disease recurrence evidence or any cause-induced mortality.
  measure: EFFICACY: Overall survival (OS)
  time frame: Baseline up to approximately 3 years
  description: Overall survival (OS): The duration from randomization to mortality caused by any underlying factors serves as a crucial metric for evaluating the impact of interventions on study participants.
  measure: EFFICACY: Two-year and three-year RFS rates
  time frame: Baseline up to approximately 2-3 years
  description: Two-year and three-year RFS rates: The two-year and three-year RFS rate represents the proportion of patients, within a specified study population, who remain free from disease recurrence for at least two or three year following a designated treatment or intervention.
  measure: EFFICACY and SAFETY: Graft survival
  time frame: Baseline up to approximately 3 years
  description: Graft survival: The interval between the commencement of randomization and the occurrence of graft loss is a pivotal time frame in transplantation research. In cases where patients are unaware of graft loss or when graft loss is not documented upon patient demise without confirmed graft loss, the time of graft loss is retrospectively evaluated using either the date of the last documented contact or the date of death.
  measure: QUALITY OF LIFE：Quality of life evaluation
  time frame: Baseline up to approximately 3 years
  description: Quality of life evaluation (QoL) according by FACT-Hep.
  measure: SAFETY: Incidence of adverse events and serious adverse events
  time frame: Baseline up to approximately 3 years
  description: Incidence of adverse events and serious adverse events. Grade by CTCAE 5.0.
  arm group label: multi-kinase inhibitors in combination with bevacizumab
  arm group type: Experimental
  description: TKI (Sorafenib 400mg, bid, po or Lenvatinib 8mg, qd, po if bodyweight less than 60 kg,12mg, qd, po if bodyweight more than 60kg or Donafenib：200mg, bid, po) + bevacizumab：7.5mg/kg, infusion, Q3w
  arm group label: Without adjuvant therapy
  arm group type: No Intervention
  description: No intervention.
  intervention type: Drug
  intervention name: multi-kinase inhibitors in combination with bevacizumab
  description: The eligible participants will start taking multi-kinase inhibitors between 4-8 weeks after liver transplantation. The choice of the specific multi-kinase inhibitor, including sorafenib, lenvatinib, or regorafenib, will be determined by the researchers based on factors such as the participant's tumor characteristics, liver function, physical condition, risk of side effects, economic status, and personal preference. The specific dosage and administration details can be found in the table provided. The maximum duration of multi-kinase inhibitor treatment will be 12 months or until any of the following conditions occur, whichever comes first: 1) The participant experiences intolerable toxic reactions that do not alleviate with dose adjustments, or 2) The participant has documented disease recurrence confirmed through imaging or withdraws from the study for other reasons.
  arm group label: multi-kinase inhibitors in combination with bevacizumab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: haitao zhao
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: haitao zhao
  phone: 01069156874
  email: zhaoht@pumch.cn
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma, Hepatocellular
  mesh term: Osteosarcoma
  mesh term: Bevacizumab