<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/NCT04443309</url>
  </required_header>
  <id_info>
    <org_study_id>JS-2286</org_study_id>
    <nct_id>NCT04443309</nct_id>
  </id_info>
  <brief_title>Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced HCC</brief_title>
  <official_title>A Single-arm, Non-randomized, Single-center Study to Evaluate Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</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 single arm, open-label, non-randomized and single-center phase I/II clinical study,&#xD;
      to evaluate the the safety, tolerance and efficacy of Lenvatinib plus Camrelizumab as&#xD;
      first-line therapy in patients with advanced Hepatocellular Carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to evaluate the safety, tolerance and efficacy of Lenvatinib&#xD;
      combined with Camrelizumab as first-line therapy for patients with advanced hepatocellular&#xD;
      carcinoma.The target sample size is 53.In the first phase 6 panticipants was evaluated&#xD;
      (N=3+3), If there was no obvious dose-limiting toxicity (DLT), then entered the extended&#xD;
      phase (N=47).Treatment continually until disease progression or intolerable toxicity or&#xD;
      patients withdrawal of consent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 11, 2020</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</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>Objective Response Rate (ORR)</measure>
    <time_frame>one year</time_frame>
    <description>Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>one year</time_frame>
    <description>Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>one year</time_frame>
    <description>A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>one year</time_frame>
    <description>Duration from the date of initial treatment to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>one year</time_frame>
    <description>Duration from the first time reported partial response or complete response to the first time of disease progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>two years</time_frame>
    <description>Proportion of patients achieved complete response and partial response for more than 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3-months and 6-months Progression Free Survival Rate</measure>
    <time_frame>6 months</time_frame>
    <description>Portion of patients who do not experience disease progression (defined by RECIST 1.1) or death of any cause after treated with toripalimab plus lenvatinib for 3 months and 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-months and 1-year Mortality Rate</measure>
    <time_frame>one year</time_frame>
    <description>Portion of patients who die of any cause after treated with toripalimab plus lenvatinib at 6 months and 1 year, respectively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AE)</measure>
    <time_frame>two years</time_frame>
    <description>Any adverse events related with treatment drugs and details include adverse events type, frequency and severity</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Biomarker</measure>
    <time_frame>two years</time_frame>
    <description>Biomarkers (such as AFP, PD-L1 expression, CD8 T cell immunohistochemistry, RNA-sequencing) related with efficacy</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">53</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Lenvatinib plus Camrelizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody.&#xD;
Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Camrelizumab</intervention_name>
    <description>Camrelizumab 200mg,iv,d1,q2w</description>
    <arm_group_label>Lenvatinib plus Camrelizumab</arm_group_label>
    <other_name>SHR-1210</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenvatinib</intervention_name>
    <description>Lenvatinib 8mg (&lt;60kg) or 12mg (≥60kg),po,d2,qd</description>
    <arm_group_label>Lenvatinib plus Camrelizumab</arm_group_label>
    <other_name>LENVIMA,E7080</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Voluntary agreement to provide written informed consent and the willingness and&#xD;
             ability to comply with all aspects of the protocol;&#xD;
&#xD;
          2. Males or females, age ≥ 18 years at the time of informed consent;&#xD;
&#xD;
          3. Imaging (by AASLD or Standard for the diagnosis and treatment of primary liver cancer&#xD;
             2017 in China) or histopathologically or cytologically confirmed advanced HCC;&#xD;
&#xD;
          4. BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed&#xD;
             following surgical and/or local therapy;&#xD;
&#xD;
          5. No previous systematic treatment for HCC;&#xD;
&#xD;
          6. Have at least one measurable lesion (in accordance with RECIST v1.1); the measurable&#xD;
             lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in&#xD;
             spiral CT scan;&#xD;
&#xD;
          7. ECOG-PS score 0 or 1&#xD;
&#xD;
          8. Child-Pugh Class: Grade A&#xD;
&#xD;
          9. Life Expectancy of at least 3 months&#xD;
&#xD;
         10. Subjects with HBV infection: HBV DNA&lt;2000 IU/ml or &lt;10^4 copy/mL, and have received&#xD;
             anti-HBV therapy for at least 14 days prior to enrollment in the study, subjects with&#xD;
             HCV-RNA(+) must receive antiviral therapy;&#xD;
&#xD;
         11. Hematology and organ functions are sufficient based on the following laboratory&#xD;
             results within 14 days prior to the treatment of this study:&#xD;
&#xD;
             Whole blood cell examination (no blood transfusion within 14 days, no G-CSF use and no&#xD;
             drugs use): WBC ≥ 3.0×10^9/L, HB ≥ 85 g/L; Neutrophils ≥ 1.5×10^9/L; PLT≥75×10^9/L;&#xD;
             Biochemical examination (no ALB infused within 14 days): ALB ≥ 29 g/L; ALP and ALT and&#xD;
             AST &lt; 5×ULN; TBIL≤3×ULN; Adequate renal function: Cr≤1.5×ULN, or CCr&gt;50mL/min; Female:&#xD;
             CrCl = ((140- year) x weight (kg) x 0.85)/72x Cr (mg/dL) Male: CrCl = ((140- year) x&#xD;
             weight (kg) x 1.00)/72xCr (mg/dL)&#xD;
&#xD;
         12. Agree to abstain from sex (avoid heterosexual intercourse) or use contraceptive&#xD;
             methods with an annual contraceptive failure rate of less than 1% during treatment and&#xD;
             for at least 6 months after the last administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hepatocellular carcinoma patients with any of the following:&#xD;
&#xD;
             Suitable for radical surgery; without an assessment lesion after radical surgery;&#xD;
             liver transplantation history or ready for liver transplantation;&#xD;
&#xD;
          2. History of hepatic encephalopathy;&#xD;
&#xD;
          3. Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar&#xD;
             cell carcinoma;&#xD;
&#xD;
          4. Pregnant women (positive pregnancy test before taking medicine) or lactating women;&#xD;
&#xD;
          5. Known history of serious allergy to any monoclonal antibody or targeted&#xD;
             anti-angiogenic drug (or any excipient);&#xD;
&#xD;
          6. Received any topical treatment within 4 weeks prior to the study, including but not&#xD;
             limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery&#xD;
             perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection;&#xD;
&#xD;
          7. Previous or existing CTCAE 5.0 standard grade 3 or above gastrointestinal fistula or&#xD;
             non-gastrointestinal fistula (such as skin);&#xD;
&#xD;
          8. Factors to affect oral administration and absorption (such as inability to swallow,&#xD;
             chronic diarrhea and intestinal obstruction);&#xD;
&#xD;
          9. Ascites with clinical symptoms (i.e. ascites with Child-Pugh rating &gt; 2) or cancerous&#xD;
             ascites require therapeutic abdominal puncture or drainage. Or uncontrolled malignant&#xD;
             ascites (ascites that researchers believe diuretics or puncture cannot control);&#xD;
&#xD;
         10. Major surgical operations (except biopsy) were performed within 4 weeks prior to the&#xD;
             first study of drug therapy or the surgical incision was not completely healed; Minor&#xD;
             surgery (i.e. simple resection, biopsy, etc.) was performed within 7 days before the&#xD;
             first round of research intervention.&#xD;
&#xD;
         11. Cardiovascular and cerebrovascular diseases with significant clinical significance,&#xD;
             including but not limited to acute myocardial infarction, severe/unstable angina&#xD;
             pectoris, cerebrovascular accident or transient ischemic attack, congestive heart&#xD;
             failure occurred within 6 months prior to admission (New York Heart Association Grade&#xD;
             ≥2, see Appendix 4); Arrhythmia requiring antiarrhythmic drugs (except β receptor&#xD;
             blocker or digoxin); Repeated ECG detection QTcF interval&gt;480 milliseconds (ms).&#xD;
&#xD;
         12. Hepatic and renal insufficiency, such as jaundice, ascites, and/or bilirubin&gt;3×ULN,&#xD;
             creatinine ratio&gt;3.5g/24h, or renal failure requiring blood or peritoneal dialysis,&#xD;
             etc. And/or urine routine showed proteinuria ≥++or confirmed 24-hour proteinuria&gt;1.0g.&#xD;
&#xD;
         13. Persistent&gt;2 grade (CTC-AE5.0) infection.&#xD;
&#xD;
         14. History of thromboembolism (including stroke and/or transient ischemic attack) in the&#xD;
             past 6 months.&#xD;
&#xD;
         15. Hypertension (systolic blood pressure&gt;160mmHg, diastolic blood pressure&gt;100 mmHg) that&#xD;
             not be well controlled through antihypertensive drug treatment.&#xD;
&#xD;
         16. History of active autoimmune diseases or autoimmune diseases in the past two years.&#xD;
&#xD;
         17. Known central nervous system metastasis and/or cancerous meningitis.&#xD;
&#xD;
         18. Be ready for or previously received organ or allogenic bone marrow transplantation.&#xD;
&#xD;
         19. Known history of active tuberculosis (Mycobacterium tuberculosis).&#xD;
&#xD;
         20. History of gastrointestinal hemorrhage within 6 months prior to the start of study&#xD;
             treatment or clear tendency of gastrointestinal hemorrhage.&#xD;
&#xD;
         21. History of human immunodeficiency virus (HIV)infection.&#xD;
&#xD;
         22. Active hepatitis B virus or C virus infection and not receive regular treatment;&#xD;
&#xD;
         23. Serious non-healing wound, ulcer or fracture.&#xD;
&#xD;
         24. Drug abuse exists; or any medical, psychological or social condition that may affect&#xD;
             research, unstable patient compliance or even endanger patient safety.&#xD;
&#xD;
         25. Any&gt;1 grade (CTC-AE 5.0) unresolved toxicity due to previous treatment or operation,&#xD;
             except for hair loss, anemia, and hypothyroidism.&#xD;
&#xD;
         26. Previous and current evidence of pulmonary fibrosis, interstitial pneumonia,&#xD;
             pneumoconiosis, radiation pneumonitis, drug-associated pneumonia and severe impairment&#xD;
             of lung function.&#xD;
&#xD;
         27. Received a potent CYP3A4 inhibitor treatment within 7 days prior to the study or&#xD;
             received a potent CYP3A4 inducer within 12 days prior to the study.&#xD;
&#xD;
         28. With other active malignant tumors except HCC within 5 years or simultaneously.&#xD;
&#xD;
         29. Patients are unsuitable for participation in this research after comprehensive&#xD;
             assessment by the researchers.&#xD;
&#xD;
         30. Patients participate in another clinical study at the same time.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Haitao Zhao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiaobo Yang</last_name>
    <phone>010-69156043</phone>
    <email>yangxulcyx@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xiao-Bo Yang</last_name>
    <phone>010-69156043</phone>
    <email>yangxiaobo67@pumch.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chinese Academy of Medical Sciences &amp; Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Please Select</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaobo Yang, MD</last_name>
      <phone>010-69156043</phone>
      <phone_ext>010-69156043</phone_ext>
      <email>yangxulcyx@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Haitao Zhao, MD</last_name>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. doi: 10.1056/NEJMra1713263. No abstract available.</citation>
    <PMID>30970190</PMID>
  </reference>
  <reference>
    <citation>Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.</citation>
    <PMID>25220842</PMID>
  </reference>
  <reference>
    <citation>Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20.</citation>
    <PMID>22353262</PMID>
  </reference>
  <reference>
    <citation>Llovet JM, Montal R, Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J Hepatol. 2019 Jun;70(6):1262-1277. doi: 10.1016/j.jhep.2019.01.028. Epub 2019 Mar 31.</citation>
    <PMID>30943423</PMID>
  </reference>
  <reference>
    <citation>Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.</citation>
    <PMID>18650514</PMID>
  </reference>
  <reference>
    <citation>Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.</citation>
    <PMID>19095497</PMID>
  </reference>
  <reference>
    <citation>Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.</citation>
    <PMID>29433850</PMID>
  </reference>
  <reference>
    <citation>8. Qin S OX, Bai Y, Cheng Y, Chen Z, Ren Z, Song T, Dutcus C, Saito K, Tamai T, Yau TCC, Rau K-M, Cheng A-L, Han G. Subgroup analysis of Chinese patients in a phase 3 study of lenvatinib vs sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma. Hepatol Int 2019;13:S170.</citation>
  </reference>
  <reference>
    <citation>Boussiotis VA. Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway. N Engl J Med. 2016 Nov 3;375(18):1767-1778. doi: 10.1056/NEJMra1514296. No abstract available.</citation>
    <PMID>27806234</PMID>
  </reference>
  <reference>
    <citation>Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016 May 27;9(1):47. doi: 10.1186/s13045-016-0277-y.</citation>
    <PMID>27234522</PMID>
  </reference>
  <reference>
    <citation>Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.</citation>
    <PMID>32402160</PMID>
  </reference>
  <reference>
    <citation>Qin S, Ren Z, Meng Z, Chen Z, Chai X, Xiong J, Bai Y, Yang L, Zhu H, Fang W, Lin X, Chen X, Li E, Wang L, Chen C, Zou J. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020 Apr;21(4):571-580. doi: 10.1016/S1470-2045(20)30011-5. Epub 2020 Feb 26.</citation>
    <PMID>32112738</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>March 27, 2023</last_update_submitted>
  <last_update_submitted_qc>March 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Lenvatinib</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04443309
org study id: JS-2286
nct id: NCT04443309
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a single arm, open-label, non-randomized and single-center phase I/II clinical study,
      to evaluate the the safety, tolerance and efficacy of Lenvatinib plus Camrelizumab as
      first-line therapy in patients with advanced Hepatocellular Carcinoma.
The purpose of this study is to evaluate the safety, tolerance and efficacy of Lenvatinib
      combined with Camrelizumab as first-line therapy for patients with advanced hepatocellular
      carcinoma.The target sample size is 53.In the first phase 6 panticipants was evaluated
      (N=3+3), If there was no obvious dose-limiting toxicity (DLT), then entered the extended
      phase (N=47).Treatment continually until disease progression or intolerable toxicity or
      patients withdrawal of consent.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: one year
description: Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
measure: Disease Control Rate (DCR)
time frame: one year
description: Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit
measure: Progression-free Survival (PFS)
time frame: one year
description: A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause
measure: Overall Survival (OS)
time frame: one year
description: Duration from the date of initial treatment to the date of death due to any cause.
measure: Duration of Response (DOR)
time frame: one year
description: Duration from the first time reported partial response or complete response to the first time of disease progression or death
measure: Clinical Benefit Rate (CBR)
time frame: two years
description: Proportion of patients achieved complete response and partial response for more than 6 months
measure: 3-months and 6-months Progression Free Survival Rate
time frame: 6 months
description: Portion of patients who do not experience disease progression (defined by RECIST 1.1) or death of any cause after treated with toripalimab plus lenvatinib for 3 months and 6 months
measure: 6-months and 1-year Mortality Rate
time frame: one year
description: Portion of patients who die of any cause after treated with toripalimab plus lenvatinib at 6 months and 1 year, respectively
measure: Adverse Events (AE)
time frame: two years
description: Any adverse events related with treatment drugs and details include adverse events type, frequency and severity
measure: Biomarker
time frame: two years
description: Biomarkers (such as AFP, PD-L1 expression, CD8 T cell immunohistochemistry, RNA-sequencing) related with efficacy
arm group label: Lenvatinib plus Camrelizumab
arm group type: Experimental
description: Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody.
Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.
intervention type: Drug
intervention name: Camrelizumab
description: Camrelizumab 200mg,iv,d1,q2w
arm group label: Lenvatinib plus Camrelizumab
other name: SHR-1210
intervention type: Drug
intervention name: Lenvatinib
description: Lenvatinib 8mg (<60kg) or 12mg (≥60kg),po,d2,qd
arm group label: Lenvatinib plus Camrelizumab
other name: LENVIMA,E7080
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Haitao Zhao, MD
role: Principal Investigator
affiliation: Peking Union Medical College Hospital
last name: Xiaobo Yang
phone: 010-69156043
email: yangxulcyx@163.com
last name: Xiao-Bo Yang
phone: 010-69156043
email: yangxiaobo67@pumch.cn
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
citation: Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. doi: 10.1056/NEJMra1713263. No abstract available.
PMID: 30970190
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responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Lenvatinib