<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/NCT03295500</url>
  </required_header>
  <id_info>
    <org_study_id>duanxuezhang</org_study_id>
    <nct_id>NCT03295500</nct_id>
  </id_info>
  <brief_title>On the Cyberknife Dose Fraction of Liver Cancer Treatment</brief_title>
  <official_title>On the Cyberknife Dose Fraction of Liver Cancer Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing 302 Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing 302 Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The research aims to the primary hepatic carcinoma patients whose diameter of the single&#xD;
      tumor is equal or less than 5cm.By supervising the changes of liver function, Child-Pugh&#xD;
      score, ICG-R15 value, secondary reaction, incidence rate of RILD during and after the&#xD;
      radiotherapy, meanwhile combining the outcome of the progression of disease and the condition&#xD;
      of survival quality, the optimum proposal could be obtained and apply to clinic thus make the&#xD;
      treatment safe, effective and personalized.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Actual">September 24, 2021</completion_date>
  <primary_completion_date type="Actual">September 10, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Local control rate</measure>
    <time_frame>From date of the participants completing the therapy until the date of first documented progression, assessed up to 36 months.</time_frame>
    <description>Local control illustrates the time from the tumor appearance to progress (the diameter more than or equal to 1.5 times of original) .The ratio of the number of the local control patients to the whole number of patients is local control rate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival rate</measure>
    <time_frame>From date of the participants diagnosed until the date of death from any cause, assessed up to 36 months.</time_frame>
    <description>Overall survival rate means the ratio of the number of patients who are alive to the whole patients after the treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RILD rate</measure>
    <time_frame>From the date of radiotherapy completion until the 4 months after therapy,up to 6 months.</time_frame>
    <description>the rate of radiotherapy induced liver disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child-Pugh score</measure>
    <time_frame>From the date of radiotherapy completion until the 4 months after therapy,up to 6 months.</time_frame>
    <description>By testing the liver function,coagulation function and ascites,we could calculate the Child-Pugh score,which reflect the liver function roundly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the value of ICG R15</measure>
    <time_frame>From the date of radiotherapy completion until the 4 months after therapy,up to 6 months.</time_frame>
    <description>It means the indocyanine green retention rate at 15 minutes,which reflects the liver reserve.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">657</enrollment>
  <condition>CyberKnife Radiosurgery</condition>
  <arm_group>
    <arm_group_label>Experimental Group One</arm_group_label>
    <description>In this group ,the participants receive the dose fraction of 49Gy/7f (BED 83.3Gy) by cyberknife.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental Group Two</arm_group_label>
    <description>In this group ,the participants receive the dose fraction of 54Gy/6f(BED 102.6Gy) by cyberknife.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <description>In this group ,the participants receive the dose fraction of 55Gy/5f(115.5Gy) by cyberknife.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Dose fraction forms</intervention_name>
    <description>The investigators divide the participants randomly into 3 groups by SPSS 19.0.Three groups participants receive the different dose fraction(49Gy/7f,54Gy/6f and 55Gy/5f),which also means different Biologic Equivalent Dose.Through the research,the investigators want to find out the optimum dose fraction method,which makes the treatment safe, effective and personalized.</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Experimental Group One</arm_group_label>
    <arm_group_label>Experimental Group Two</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators aim to the hepatocellular participants who receive the radiotherapy&#xD;
        through different dose fraction by cyberknife.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The participants are from 30 to 80 years of age, without gender restriction&#xD;
&#xD;
          -  With the hepatopathy background, the diagnosis of primary hepatic carcinoma is&#xD;
             confirmed by image examination and laboratory test(the diagnosis criteria is according&#xD;
             to the primary hepatic carcinoma rule of diagnosis and treat in 2007)&#xD;
&#xD;
          -  The max diameter of single tumor ≤5cm&#xD;
&#xD;
          -  Child-Pugh Classification(CPC) A or B&#xD;
&#xD;
          -  ECOG score 0 or 1&#xD;
&#xD;
          -  Leukocyte is more than 2×109/L and thrombocyte is more than 60×109/L&#xD;
&#xD;
          -  Kidney function is normal&#xD;
&#xD;
          -  Unsuitable or rejecting other therapies such as resection, liver transplantation etc&#xD;
&#xD;
          -  Anticipated lifetime is longer than six months&#xD;
&#xD;
          -  The participants who are voluntary comply with the requirements of research&#xD;
&#xD;
          -  The participants agree to sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The metastasis occur outside of liver&#xD;
&#xD;
          -  Child-Pugh Classification(CPC)&#xD;
&#xD;
          -  The outline of tumor is not confirmed by image examination&#xD;
&#xD;
          -  With hepatic or any other abdomen radiotherapy history before&#xD;
&#xD;
          -  With severe internal medicine diseases&#xD;
&#xD;
          -  Bone marrow haematopoietic function or kidney function is severe failure&#xD;
&#xD;
          -  Intractable ascites&#xD;
&#xD;
          -  The position of tumor is nearby esophagus, stomach or intestine&#xD;
&#xD;
          -  The normal liver volume less than 700 cm3&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CyberKnife</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100039</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Stenmark MH, Cao Y, Wang H, Jackson A, Ben-Josef E, Ten Haken RK, Lawrence TS, Feng M. Estimating functional liver reserve following hepatic irradiation: adaptive normal tissue response models. Radiother Oncol. 2014 Jun;111(3):418-23. doi: 10.1016/j.radonc.2014.04.007. Epub 2014 May 8.</citation>
    <PMID>24813090</PMID>
  </reference>
  <results_reference>
    <citation>Dewas S, Bibault JE, Mirabel X, Fumagalli I, Kramar A, Jarraya H, Lacornerie T, Dewas-Vautravers C, Lartigau E. Prognostic factors affecting local control of hepatic tumors treated by Stereotactic Body Radiation Therapy. Radiat Oncol. 2012 Oct 10;7:166. doi: 10.1186/1748-717X-7-166.</citation>
    <PMID>23050794</PMID>
  </results_reference>
  <results_reference>
    <citation>Goodman BD, Mannina EM, Althouse SK, Maluccio MA, Cardenes HR. Long-term safety and efficacy of stereotactic body radiation therapy for hepatic oligometastases. Pract Radiat Oncol. 2016 Mar-Apr;6(2):86-95. doi: 10.1016/j.prro.2015.10.011. Epub 2015 Oct 23.</citation>
    <PMID>26725957</PMID>
  </results_reference>
  <results_reference>
    <citation>Liang P, Huang C, Liang SX, Li YF, Huang SX, Lian ZP, Liu JM, Tang Y, Lu HJ. Effect of CyberKnife stereotactic body radiation therapy for hepatocellular carcinoma on hepatic toxicity. Onco Targets Ther. 2016 Nov 18;9:7169-7175. doi: 10.2147/OTT.S112290. eCollection 2016.</citation>
    <PMID>27920555</PMID>
  </results_reference>
  <results_reference>
    <citation>Su TS, Lu HZ, Cheng T, Zhou Y, Huang Y, Gao YC, Tang MY, Jiang HY, Lian ZP, Hou EC, Liang P. Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma &gt;5 cm. BMC Cancer. 2016 Nov 3;16(1):834. doi: 10.1186/s12885-016-2894-9.</citation>
    <PMID>27809890</PMID>
  </results_reference>
  <results_reference>
    <citation>Que J, Kuo HT, Lin LC, Lin KL, Lin CH, Lin YW, Yang CC. Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma. BMC Cancer. 2016 Jul 12;16:451. doi: 10.1186/s12885-016-2512-x.</citation>
    <PMID>27405814</PMID>
  </results_reference>
  <results_reference>
    <citation>Schoenberg M, Khandoga A, Stintzing S, Trumm C, Schiergens TS, Angele M, Op den Winkel M, Werner J, Muacevic A, Rentsch M. CyberKnife Radiosurgery - Value as an Adjunct to Surgical Treatment of HCC? Cureus. 2016 Apr 28;8(4):e591. doi: 10.7759/cureus.591.</citation>
    <PMID>27284498</PMID>
  </results_reference>
  <results_reference>
    <citation>Su TS, Liang P, Lu HZ, Liang J, Gao YC, Zhou Y, Huang Y, Tang MY, Liang JN. Stereotactic body radiation therapy for small primary or recurrent hepatocellular carcinoma in 132 Chinese patients. J Surg Oncol. 2016 Feb;113(2):181-7. doi: 10.1002/jso.24128. Epub 2015 Dec 14.</citation>
    <PMID>26799260</PMID>
  </results_reference>
  <results_reference>
    <citation>Lo CH, Huang WY, Lin KT, Lin MJ, Lin TP, Jen YM. Repeated stereotactic ablative radiotherapy using CyberKnife for patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2014 Nov;29(11):1919-25. doi: 10.1111/jgh.12659.</citation>
    <PMID>25041220</PMID>
  </results_reference>
  <results_reference>
    <citation>Que JY, Lin LC, Lin KL, Lin CH, Lin YW, Yang CC. The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities. Radiat Oncol. 2014 May 28;9:120. doi: 10.1186/1748-717X-9-120.</citation>
    <PMID>24885086</PMID>
  </results_reference>
  <results_reference>
    <citation>Lo CH, Huang WY, Lee MS, Lin KT, Lin TP, Chang PY, Fan CY, Jen YM. Stereotactic ablative radiotherapy for unresectable hepatocellular carcinoma patients who failed or were unsuitable for transarterial chemoembolization. Eur J Gastroenterol Hepatol. 2014 Mar;26(3):345-52. doi: 10.1097/MEG.0000000000000032.</citation>
    <PMID>24384685</PMID>
  </results_reference>
  <results_reference>
    <citation>Bibault JE, Dewas S, Vautravers-Dewas C, Hollebecque A, Jarraya H, Lacornerie T, Lartigau E, Mirabel X. Stereotactic body radiation therapy for hepatocellular carcinoma: prognostic factors of local control, overall survival, and toxicity. PLoS One. 2013 Oct 11;8(10):e77472. doi: 10.1371/journal.pone.0077472. eCollection 2013.</citation>
    <PMID>24147002</PMID>
  </results_reference>
  <results_reference>
    <citation>Yoon HI, Koom WS, Lee IJ, Jeong K, Chung Y, Kim JK, Lee KS, Han KH, Seong J. The significance of ICG-R15 in predicting hepatic toxicity in patients receiving radiotherapy for hepatocellular carcinoma. Liver Int. 2012 Aug;32(7):1165-71. doi: 10.1111/j.1478-3231.2012.02784.x. Epub 2012 Mar 21.</citation>
    <PMID>22435801</PMID>
  </results_reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>September 16, 2017</study_first_submitted>
  <study_first_submitted_qc>September 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>October 18, 2021</last_update_submitted>
  <last_update_submitted_qc>October 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CyberKnife</keyword>
  <keyword>hepatocellular</keyword>
  <keyword>dose fraction</keyword>
  <keyword>ICG R15</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Neoplasms</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/NCT03295500
org study id: duanxuezhang
nct id: NCT03295500
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The research aims to the primary hepatic carcinoma patients whose diameter of the single
      tumor is equal or less than 5cm.By supervising the changes of liver function, Child-Pugh
      score, ICG-R15 value, secondary reaction, incidence rate of RILD during and after the
      radiotherapy, meanwhile combining the outcome of the progression of disease and the condition
      of survival quality, the optimum proposal could be obtained and apply to clinic thus make the
      treatment safe, effective and personalized.
observational model: Other
time perspective: Prospective
measure: Local control rate
time frame: From date of the participants completing the therapy until the date of first documented progression, assessed up to 36 months.
description: Local control illustrates the time from the tumor appearance to progress (the diameter more than or equal to 1.5 times of original) .The ratio of the number of the local control patients to the whole number of patients is local control rate.
measure: Overall survival rate
time frame: From date of the participants diagnosed until the date of death from any cause, assessed up to 36 months.
description: Overall survival rate means the ratio of the number of patients who are alive to the whole patients after the treatment.
measure: RILD rate
time frame: From the date of radiotherapy completion until the 4 months after therapy,up to 6 months.
description: the rate of radiotherapy induced liver disease
measure: Child-Pugh score
time frame: From the date of radiotherapy completion until the 4 months after therapy,up to 6 months.
description: By testing the liver function,coagulation function and ascites,we could calculate the Child-Pugh score,which reflect the liver function roundly.
measure: the value of ICG R15
time frame: From the date of radiotherapy completion until the 4 months after therapy,up to 6 months.
description: It means the indocyanine green retention rate at 15 minutes,which reflects the liver reserve.
arm group label: Experimental Group One
description: In this group ,the participants receive the dose fraction of 49Gy/7f (BED 83.3Gy) by cyberknife.
arm group label: Experimental Group Two
description: In this group ,the participants receive the dose fraction of 54Gy/6f(BED 102.6Gy) by cyberknife.
arm group label: Control Group
description: In this group ,the participants receive the dose fraction of 55Gy/5f(115.5Gy) by cyberknife.
intervention type: Radiation
intervention name: Dose fraction forms
description: The investigators divide the participants randomly into 3 groups by SPSS 19.0.Three groups participants receive the different dose fraction(49Gy/7f,54Gy/6f and 55Gy/5f),which also means different Biologic Equivalent Dose.Through the research,the investigators want to find out the optimum dose fraction method,which makes the treatment safe, effective and personalized.
arm group label: Control Group
arm group label: Experimental Group One
arm group label: Experimental Group Two
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
citation: Stenmark MH, Cao Y, Wang H, Jackson A, Ben-Josef E, Ten Haken RK, Lawrence TS, Feng M. Estimating functional liver reserve following hepatic irradiation: adaptive normal tissue response models. Radiother Oncol. 2014 Jun;111(3):418-23. doi: 10.1016/j.radonc.2014.04.007. Epub 2014 May 8.
PMID: 24813090
citation: Dewas S, Bibault JE, Mirabel X, Fumagalli I, Kramar A, Jarraya H, Lacornerie T, Dewas-Vautravers C, Lartigau E. Prognostic factors affecting local control of hepatic tumors treated by Stereotactic Body Radiation Therapy. Radiat Oncol. 2012 Oct 10;7:166. doi: 10.1186/1748-717X-7-166.
PMID: 23050794
citation: Goodman BD, Mannina EM, Althouse SK, Maluccio MA, Cardenes HR. Long-term safety and efficacy of stereotactic body radiation therapy for hepatic oligometastases. Pract Radiat Oncol. 2016 Mar-Apr;6(2):86-95. doi: 10.1016/j.prro.2015.10.011. Epub 2015 Oct 23.
PMID: 26725957
citation: Liang P, Huang C, Liang SX, Li YF, Huang SX, Lian ZP, Liu JM, Tang Y, Lu HJ. Effect of CyberKnife stereotactic body radiation therapy for hepatocellular carcinoma on hepatic toxicity. Onco Targets Ther. 2016 Nov 18;9:7169-7175. doi: 10.2147/OTT.S112290. eCollection 2016.
PMID: 27920555
citation: Su TS, Lu HZ, Cheng T, Zhou Y, Huang Y, Gao YC, Tang MY, Jiang HY, Lian ZP, Hou EC, Liang P. Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma >5 cm. BMC Cancer. 2016 Nov 3;16(1):834. doi: 10.1186/s12885-016-2894-9.
PMID: 27809890
citation: Que J, Kuo HT, Lin LC, Lin KL, Lin CH, Lin YW, Yang CC. Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma. BMC Cancer. 2016 Jul 12;16:451. doi: 10.1186/s12885-016-2512-x.
PMID: 27405814
citation: Schoenberg M, Khandoga A, Stintzing S, Trumm C, Schiergens TS, Angele M, Op den Winkel M, Werner J, Muacevic A, Rentsch M. CyberKnife Radiosurgery - Value as an Adjunct to Surgical Treatment of HCC? Cureus. 2016 Apr 28;8(4):e591. doi: 10.7759/cureus.591.
PMID: 27284498
citation: Su TS, Liang P, Lu HZ, Liang J, Gao YC, Zhou Y, Huang Y, Tang MY, Liang JN. Stereotactic body radiation therapy for small primary or recurrent hepatocellular carcinoma in 132 Chinese patients. J Surg Oncol. 2016 Feb;113(2):181-7. doi: 10.1002/jso.24128. Epub 2015 Dec 14.
PMID: 26799260
citation: Lo CH, Huang WY, Lin KT, Lin MJ, Lin TP, Jen YM. Repeated stereotactic ablative radiotherapy using CyberKnife for patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2014 Nov;29(11):1919-25. doi: 10.1111/jgh.12659.
PMID: 25041220
citation: Que JY, Lin LC, Lin KL, Lin CH, Lin YW, Yang CC. The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities. Radiat Oncol. 2014 May 28;9:120. doi: 10.1186/1748-717X-9-120.
PMID: 24885086
citation: Lo CH, Huang WY, Lee MS, Lin KT, Lin TP, Chang PY, Fan CY, Jen YM. Stereotactic ablative radiotherapy for unresectable hepatocellular carcinoma patients who failed or were unsuitable for transarterial chemoembolization. Eur J Gastroenterol Hepatol. 2014 Mar;26(3):345-52. doi: 10.1097/MEG.0000000000000032.
PMID: 24384685
citation: Bibault JE, Dewas S, Vautravers-Dewas C, Hollebecque A, Jarraya H, Lacornerie T, Lartigau E, Mirabel X. Stereotactic body radiation therapy for hepatocellular carcinoma: prognostic factors of local control, overall survival, and toxicity. PLoS One. 2013 Oct 11;8(10):e77472. doi: 10.1371/journal.pone.0077472. eCollection 2013.
PMID: 24147002
citation: Yoon HI, Koom WS, Lee IJ, Jeong K, Chung Y, Kim JK, Lee KS, Han KH, Seong J. The significance of ICG-R15 in predicting hepatic toxicity in patients receiving radiotherapy for hepatocellular carcinoma. Liver Int. 2012 Aug;32(7):1165-71. doi: 10.1111/j.1478-3231.2012.02784.x. Epub 2012 Mar 21.
PMID: 22435801
responsible party type: Sponsor
mesh term: Liver Neoplasms
sharing ipd: No