<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/NCT02237924</url>
  </required_header>
  <id_info>
    <org_study_id>S201413__19</org_study_id>
    <nct_id>NCT02237924</nct_id>
  </id_info>
  <brief_title>Endostar Combined With Intensity-modulated Radiotherapy Compare With Chemoradiation for Nasopharyngeal Carcinoma</brief_title>
  <official_title>Effect of Endostar Combined With Intensity-modulated Radiotherapy Compare With Chemoradiation for Locoregionally Advanced,Low-risk Nasopharyngeal Carcinoma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital of Guangxi Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First Affiliated Hospital of Guangxi Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A total of 120 patients with pathologically confirmed locally advanced low-risk&#xD;
      nasopharyngeal carcinoma were enrolled. They were randomly divided into two groups, with 60&#xD;
      patients in each group. One group was treated with intensity-modulated radiation therapy&#xD;
      (IMRT) combined with Endostar and the other group was treated with IMRT combined with&#xD;
      concurrent chemotherapy. The short term efficacy and the toxic and side effects of these&#xD;
      treatments were evaluated. The 1-year, 3-year, 5-year overall survival and progression-free&#xD;
      survival of patients were analyzed. Our data may provide an alternative option for the&#xD;
      treatment of locally advanced low-risk nasopharyngeal carcinoma with high efficacy and low&#xD;
      toxicity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was a multicenter, open-label, randomized controlled clinical trial. A set of&#xD;
      unified standards were used, including the clinical research program, inclusion criteria,&#xD;
      exclusion criteria, chemoradiotherapy regimen and evaluation criteria. Nine medical centers&#xD;
      participated in this study and 120 patients with pathologically confirmed locally advanced&#xD;
      low-risk nasopharyngeal carcinoma were enrolled. These patients were stratified according to&#xD;
      clinical stage and participating center, and were randomly divided into two groups: IMRT&#xD;
      combined with Endostar group ( IMRT 70-74Gy, Endostar 7.5mg / m2, 2 cycles of continuous&#xD;
      intravenous pumping, and 2 cycles of maintenance therapy after radiotherapy) and IMRT&#xD;
      combined with concurrent chemotherapy group ( IMRT 70-74Gy, DDP 100mg / m2, intravenous&#xD;
      infusion over 2 hours , for 2-3 cycles). After treatment, follow-up was performed every 3&#xD;
      months. The treatment toxicity, local control rate, distant metastasis-free survival, overall&#xD;
      survival, progression-free survival were observed and assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">January 2022</completion_date>
  <primary_completion_date type="Actual">September 2021</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>5-year Overall Survival</measure>
    <time_frame>6 years</time_frame>
    <description>The subjects were randomly divided into two groups. Group A: IMRT combined with Endostar ，including 2 cycles of continuous intravenous pumping, and 2 cycles of maintenance therapy after radiotherapy，and Group B: IMRT combined with concurrent chemotherapy for 2 or 3 cycles. After treatment, the subjects go to observation period for 5 years.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>3-year Progression Free Survival</measure>
    <time_frame>4 years</time_frame>
    <description>The subjects were randomly divided into two groups. Group A: IMRT combined with Endostar ，including 2 cycles of continuous intravenous pumping, and 2 cycles of maintenance therapy after radiotherapy，and Group B: IMRT combined with concurrent chemotherapy for 2 or 3 cycles. After treatment, the subjects go into observation period. MRI will be used for evaluating the carcinoma status. During 3 years, any relapse or death will be recorded.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <arm_group>
    <arm_group_label>endostar + IMRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>DDP + IMRT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>endostar</intervention_name>
    <description>Endostar 7.5mg / m2, 2 cycles of continuous intravenous pumping for ten days,and 2 cycles of maintenance therapy after radiotherapy</description>
    <arm_group_label>endostar + IMRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DDP</intervention_name>
    <description>DDP:100mg/m2 for 2-3 cycles</description>
    <arm_group_label>DDP + IMRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>IMRT</intervention_name>
    <description>IMRT:70-74Gy for 2-3 cycles</description>
    <arm_group_label>DDP + IMRT</arm_group_label>
    <arm_group_label>endostar + IMRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. patients of either gender and aged from 18 to 70 years old.&#xD;
&#xD;
          2. patients with histologically confirmed non-keratinizing squamous cell nasopharyngeal&#xD;
             carcinoma.&#xD;
&#xD;
          3. patients at stage III/IVM0 by UICC2010 staging; patients with higher risk factors&#xD;
             (such as N3 and T4N2-phase lymph node ≥4 cm) were excluded.&#xD;
&#xD;
          4. KPS ≥ 70 (Appendix I)&#xD;
&#xD;
          5. patients with available MRI data of nasopharynx and measurable tumor lesions.&#xD;
&#xD;
          6. patients did not receive any treatment before enrollment.&#xD;
&#xD;
          7. patients with expected survival longer than 6 months.&#xD;
&#xD;
          8. biochemical indexes: hemoglobin &gt; 120 g/L, WBC &gt; 4 x 109 /L, and blood platelet ≥ 100&#xD;
             x 109 /L; levels of indicators for hepatic and renal function was 1.25 folds of the&#xD;
             upper limit of normal value.&#xD;
&#xD;
          9. the informed content was obtained from every patient.&#xD;
&#xD;
         10. patients with effective follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. those with malignant tumors other than nasopharyngeal carcinoma, stage I non-melanoma&#xD;
             skin cancer, and cervical carcinoma in situ.&#xD;
&#xD;
          2. those received treatments before enrollment.&#xD;
&#xD;
          3. pregnant or lactating women and reproductive women without contraception.&#xD;
&#xD;
          4. those who were undergoing other drug trials.&#xD;
&#xD;
          5. those with severe complications, including myocardial infarction, severe arrhythmia,&#xD;
             severe cerebrovascular disease, ulcer disease, mental illness and uncontrollable&#xD;
             diabetes.&#xD;
&#xD;
          6. those who could not be followed up at regular intervals.&#xD;
&#xD;
          7. those who were treated with tumor targeting drugs.&#xD;
&#xD;
          8. those who could not subject to MRI examination.&#xD;
&#xD;
          9. those who could not meet the requirements of the prescribed dose.&#xD;
&#xD;
         10. those with hemorrhagic tendency.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheng ren Wang, doctor</last_name>
    <role>Study Director</role>
    <affiliation>First Affiliated Hospital of Guangxi Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Guangxi Medical University</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <zip>530021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Lee AW, Sze WM, Au JS, Leung SF, Leung TW, Chua DT, Zee BC, Law SC, Teo PM, Tung SY, Kwong DL, Lau WH. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2005 Mar 15;61(4):1107-16. doi: 10.1016/j.ijrobp.2004.07.702.</citation>
    <PMID>15752890</PMID>
  </reference>
  <reference>
    <citation>Yeh SA, Tang Y, Lui CC, Huang YJ, Huang EY. Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone. Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):672-9. doi: 10.1016/j.ijrobp.2004.11.002.</citation>
    <PMID>15936544</PMID>
  </reference>
  <reference>
    <citation>Yi JL, Gao L, Huang XD, Li SY, Luo JW, Cai WM, Xiao JP, Xu GZ. Nasopharyngeal carcinoma treated by radical radiotherapy alone: Ten-year experience of a single institution. Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):161-8. doi: 10.1016/j.ijrobp.2005.12.003. Epub 2006 Mar 20.</citation>
    <PMID>16542792</PMID>
  </reference>
  <reference>
    <citation>Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, Chan AT, Ang KK. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2012 Feb;13(2):172-80. doi: 10.1016/S1470-2045(11)70303-5. Epub 2011 Dec 15.</citation>
    <PMID>22178121</PMID>
  </reference>
  <reference>
    <citation>Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, Leung WK. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):981-91. doi: 10.1016/j.ijrobp.2006.06.013.</citation>
    <PMID>17145528</PMID>
  </reference>
  <reference>
    <citation>Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, Yu KH, Chiu KW, Chan DT, Mok T, Yuen KT, Mo F, Lai M, Kwan WH, Choi P, Johnson PJ. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002 Apr 15;20(8):2038-44. doi: 10.1200/JCO.2002.08.149.</citation>
    <PMID>11956263</PMID>
  </reference>
  <reference>
    <citation>Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, Siu L, Sze WM, Leung TW, Sham JS, Ngan RK, Law SC, Yau TK, Au JS, O'Sullivan B, Pang ES, O SK, Au GK, Lau JT; Hong Kong Nasopharyngeal Cancer Study Group. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005 Oct 1;23(28):6966-75. doi: 10.1200/JCO.2004.00.7542.</citation>
    <PMID>16192584</PMID>
  </reference>
  <reference>
    <citation>Wen QL, Meng MB, Yang B, Tu LL, Jia L, Zhou L, Xu Y, Lu Y. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice. Cancer Sci. 2009 Aug;100(8):1510-9. doi: 10.1111/j.1349-7006.2009.01193.x. Epub 2009 May 21.</citation>
    <PMID>19459845</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>January 30, 2022</last_update_submitted>
  <last_update_submitted_qc>January 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>First Affiliated Hospital of Guangxi Medical University</investigator_affiliation>
    <investigator_full_name>min kang</investigator_full_name>
    <investigator_title>doctor</investigator_title>
  </responsible_party>
  <keyword>nasopharyngeal carcinoma</keyword>
  <keyword>endostar</keyword>
  <keyword>IMRT</keyword>
  <keyword>chemoradiation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endostar protein</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/NCT02237924
org study id: S201413__19
nct id: NCT02237924
lead sponsor: 
has dmc: Yes
A total of 120 patients with pathologically confirmed locally advanced low-risk
      nasopharyngeal carcinoma were enrolled. They were randomly divided into two groups, with 60
      patients in each group. One group was treated with intensity-modulated radiation therapy
      (IMRT) combined with Endostar and the other group was treated with IMRT combined with
      concurrent chemotherapy. The short term efficacy and the toxic and side effects of these
      treatments were evaluated. The 1-year, 3-year, 5-year overall survival and progression-free
      survival of patients were analyzed. Our data may provide an alternative option for the
      treatment of locally advanced low-risk nasopharyngeal carcinoma with high efficacy and low
      toxicity.
This study was a multicenter, open-label, randomized controlled clinical trial. A set of
      unified standards were used, including the clinical research program, inclusion criteria,
      exclusion criteria, chemoradiotherapy regimen and evaluation criteria. Nine medical centers
      participated in this study and 120 patients with pathologically confirmed locally advanced
      low-risk nasopharyngeal carcinoma were enrolled. These patients were stratified according to
      clinical stage and participating center, and were randomly divided into two groups: IMRT
      combined with Endostar group ( IMRT 70-74Gy, Endostar 7.5mg / m2, 2 cycles of continuous
      intravenous pumping, and 2 cycles of maintenance therapy after radiotherapy) and IMRT
      combined with concurrent chemotherapy group ( IMRT 70-74Gy, DDP 100mg / m2, intravenous
      infusion over 2 hours , for 2-3 cycles). After treatment, follow-up was performed every 3
      months. The treatment toxicity, local control rate, distant metastasis-free survival, overall
      survival, progression-free survival were observed and assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 5-year Overall Survival
time frame: 6 years
description: The subjects were randomly divided into two groups. Group A: IMRT combined with Endostar ，including 2 cycles of continuous intravenous pumping, and 2 cycles of maintenance therapy after radiotherapy，and Group B: IMRT combined with concurrent chemotherapy for 2 or 3 cycles. After treatment, the subjects go to observation period for 5 years.
measure: 3-year Progression Free Survival
time frame: 4 years
description: The subjects were randomly divided into two groups. Group A: IMRT combined with Endostar ，including 2 cycles of continuous intravenous pumping, and 2 cycles of maintenance therapy after radiotherapy，and Group B: IMRT combined with concurrent chemotherapy for 2 or 3 cycles. After treatment, the subjects go into observation period. MRI will be used for evaluating the carcinoma status. During 3 years, any relapse or death will be recorded.
arm group label: endostar + IMRT
arm group type: Experimental
arm group label: DDP + IMRT
arm group type: Active Comparator
intervention type: Drug
intervention name: endostar
description: Endostar 7.5mg / m2, 2 cycles of continuous intravenous pumping for ten days,and 2 cycles of maintenance therapy after radiotherapy
arm group label: endostar + IMRT
intervention type: Drug
intervention name: DDP
description: DDP:100mg/m2 for 2-3 cycles
arm group label: DDP + IMRT
intervention type: Radiation
intervention name: IMRT
description: IMRT:70-74Gy for 2-3 cycles
arm group label: DDP + IMRT
arm group label: endostar + IMRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sheng ren Wang, doctor
role: Study Director
affiliation: First Affiliated Hospital of Guangxi Medical University
facility: 
country: China
citation: Lee AW, Sze WM, Au JS, Leung SF, Leung TW, Chua DT, Zee BC, Law SC, Teo PM, Tung SY, Kwong DL, Lau WH. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2005 Mar 15;61(4):1107-16. doi: 10.1016/j.ijrobp.2004.07.702.
PMID: 15752890
citation: Yeh SA, Tang Y, Lui CC, Huang YJ, Huang EY. Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone. Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):672-9. doi: 10.1016/j.ijrobp.2004.11.002.
PMID: 15936544
citation: Yi JL, Gao L, Huang XD, Li SY, Luo JW, Cai WM, Xiao JP, Xu GZ. Nasopharyngeal carcinoma treated by radical radiotherapy alone: Ten-year experience of a single institution. Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):161-8. doi: 10.1016/j.ijrobp.2005.12.003. Epub 2006 Mar 20.
PMID: 16542792
citation: Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, Chan AT, Ang KK. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2012 Feb;13(2):172-80. doi: 10.1016/S1470-2045(11)70303-5. Epub 2011 Dec 15.
PMID: 22178121
citation: Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, Leung WK. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):981-91. doi: 10.1016/j.ijrobp.2006.06.013.
PMID: 17145528
citation: Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, Yu KH, Chiu KW, Chan DT, Mok T, Yuen KT, Mo F, Lai M, Kwan WH, Choi P, Johnson PJ. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002 Apr 15;20(8):2038-44. doi: 10.1200/JCO.2002.08.149.
PMID: 11956263
citation: Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, Siu L, Sze WM, Leung TW, Sham JS, Ngan RK, Law SC, Yau TK, Au JS, O'Sullivan B, Pang ES, O SK, Au GK, Lau JT; Hong Kong Nasopharyngeal Cancer Study Group. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005 Oct 1;23(28):6966-75. doi: 10.1200/JCO.2004.00.7542.
PMID: 16192584
citation: Wen QL, Meng MB, Yang B, Tu LL, Jia L, Zhou L, Xu Y, Lu Y. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice. Cancer Sci. 2009 Aug;100(8):1510-9. doi: 10.1111/j.1349-7006.2009.01193.x. Epub 2009 May 21.
PMID: 19459845
responsible party type: Principal Investigator
investigator affiliation: First Affiliated Hospital of Guangxi Medical University
investigator full name: min kang
investigator title: doctor
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma
mesh term: Endostar protein