<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/NCT04456322</url>
  </required_header>
  <id_info>
    <org_study_id>2020-FXY-001</org_study_id>
    <nct_id>NCT04456322</nct_id>
  </id_info>
  <brief_title>Radiotherapy Plus Nimotuzumab or Cisplatin in Nasopharyngeal Carcinoma</brief_title>
  <official_title>A Randomized Non-inferiority Trial of Radiotherapy Plus Nimotuzumab or Cisplatin in Patients With Favorable Response to Induction Chemotherapy for Low-risk Locoregionally Advanced-Staged Nasopharyngeal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</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 phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker&#xD;
      nimotuzumab versus radiotherapy plus cisplatin(CCRT) for nasopharyngeal carcinoma (NPC)&#xD;
      patients with favorable response to induction chemotheray(IC), determining whether&#xD;
      radiotherapy combined with nimotuzumab was non-inferior to CCRT and may provide new evidence&#xD;
      for individualized comprehensive treatment of locoregionally advanced NPC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently, NCCN (National Comprehensive Cancer Network) guidelines recommend induction&#xD;
      chemotherapy combined with concurrent chemoradiotherapy as IIA level-evidenced treatment for&#xD;
      locally advanced nasopharyngeal carcinoma (stage II-IVa). However, although induction&#xD;
      chemotherapy combined with cisplatin based concurrent radiotherapy (CCRT) can significantly&#xD;
      improve the survival of patients, the side effects during radiotherapy are more serious.&#xD;
&#xD;
      Previous studies have demonstrated that with a cut-off point of 1500 copies/mL, NPC patients&#xD;
      could be segregated into a low-risk subgroup and a high-risk subgroup. Besides, our previous&#xD;
      results showed that patients with plasma Epstein-Barr virus (EBV) DNA= 0 copy/mL and complete&#xD;
      response/partial response (CR/PR) after induction chemotherapy had a significantly lower risk&#xD;
      of disease progression than patients with plasma EBV DNA&gt;0 copy/mL and stable disease&#xD;
      /progressive disease (SD/PD),according to Response Evaluation Criteria in Solid Tumors&#xD;
      (RECIST). As for these low-risk and chemotheray sensitive patients, it can be considered to&#xD;
      reduce the current standard treatment intensity without affecting the survival rate of&#xD;
      patients, which reduces the side effects of patients and improve the their life qualities.&#xD;
&#xD;
      Epidermal growth factor (EGFR) is an important therapeutic target for nasopharyngeal&#xD;
      carcinoma. A retrospective study suggested that there was no significant difference in the&#xD;
      3-year overall survival between NPC patients who received nimotuzumab / cetuximab plus&#xD;
      radiotherapy and those who received standard CCRT. Besides, in terms of hepatorenal toxicity,&#xD;
      anti-EGFR drugs showed better safety compared with traditional cisplatin chemotherapy. Up to&#xD;
      now, randomized clinical trial about the application of nimotuzumab after IC is still&#xD;
      limited.&#xD;
&#xD;
      This is a phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker&#xD;
      nimotuzumab versus radiotherapy plus cisplatin for NPC patients with favorable response after&#xD;
      IC, determining whether radiotherapy combined with nimotuzumab was non-inferior to CCRT after&#xD;
      IC and may provide new evidence for individualized comprehensive treatment of locoregionally&#xD;
      advanced NPC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 6, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2023</primary_completion_date>
  <phase>Phase 3</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>Progression-Free Survival (PFS)</measure>
    <time_frame>2 years</time_frame>
    <description>Defined from date of randomization to date of first documentation of progression or death due to any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Locoregional Relapse-Free Survival (LRFS)</measure>
    <time_frame>2 years</time_frame>
    <description>Defined from date of randomization to date of first documentation of locoregional relapse or the date of death from any cause or until the date of the last follow-up visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant Metastasis-Free Survival (DMFS)</measure>
    <time_frame>2 years</time_frame>
    <description>Defined from date of randomization to date of first documentation of distant metastases or the date of death from any cause or until the date of the last follow-up visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Three months after the completion of the CCRT with or without Nimotuzumab treatment</time_frame>
    <description>An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence rate of adverse events (AEs)</measure>
    <time_frame>2 years</time_frame>
    <description>Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes</measure>
    <time_frame>2 years</time_frame>
    <description>Pre-treatment EGFR expression level and EGFR Gene Copy Number is evaluated by means of immunohistochemical testing and fluorescent in situ hybridization (FISH), respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of QoL</measure>
    <time_frame>1 years</time_frame>
    <description>QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of EORTC quality of life questionnaire(QLQ) Head and Neck score</measure>
    <time_frame>1 years</time_frame>
    <description>QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H&amp;N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva,coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.All of the scores mentioned above were assessed at the below time point:before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma EBV DNA copy number</measure>
    <time_frame>2 years</time_frame>
    <description>Plasma EBV DNA copy number in both arms was assessed by Quantitative real time polymerase chain reaction(qRT-PCR) at pretreatment, after two cycle induction chemotherapy, during CCRT and follow up time . The predictive value of plasma EBV DNA copy number was assessed by survival analysis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">326</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <arm_group>
    <arm_group_label>RT plus Nimotuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with pretreatment plasma EBV DNA&lt;1500 copy/ml and up to CR/PR according to RECIST and the EBV DNA reduced to undectable(0 copy/mL ) after two cycle induction chemotherapy ( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-FU 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RT plus Cisplatin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with pretreatment plasma EBV DNA&lt;1500 copy/ml and up to CR/PR according to RECIST and the EBV DNA reduced to undectable(0 copy/mL ) after two cycle induction chemotherapy( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-FU 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) )</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RT plus Nimotuzumab</intervention_name>
    <description>Nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)</description>
    <arm_group_label>RT plus Nimotuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RT plus Cisplatin</intervention_name>
    <description>concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy )</description>
    <arm_group_label>RT plus Cisplatin</arm_group_label>
    <other_name>Cisplatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-70, regardless of sex.&#xD;
&#xD;
          2. Patients with newly histologically confirmed non-keratinizing nasopharyngeal&#xD;
             carcinoma, type of WHO II or III, clinical stage II-IVa (except N3)(according to the&#xD;
             8th American Joint Committee on Cancer[AJCC] edition)&#xD;
&#xD;
          3. Patients with pre-treatment plasma EBV DNA&lt;1500 copies/mL&#xD;
&#xD;
          4. Patients with plasma EBV DNA= 0 copy/mL and CR/PR according to RECIST after two cycle&#xD;
             induction chemotherapy&#xD;
&#xD;
          5. ECOG (Eastern Cooperative Oncology Group) score: 0-1&#xD;
&#xD;
          6. Women in their reproductive years should ensure that they use contraception during the&#xD;
             study period.&#xD;
&#xD;
          7. Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109&#xD;
             /L.&#xD;
&#xD;
          8. Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)&lt; 2.5 times&#xD;
             the upper limit of normal value (ULN), total bilirubin &lt;2.0×ULN.&#xD;
&#xD;
          9. Renal function: serum creatinine &lt;1.5×ULN&#xD;
&#xD;
         10. Patients must sign informed consent and be willing and able to comply with the&#xD;
             requirements of visits, treatment, laboratory tests and other research requirements&#xD;
             stipulated in the research schedule;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed keratinizing squamous cell carcinoma (WHO I)&#xD;
&#xD;
          2. Receiving radiotherapy or chemotherapy or targeted therapy previously&#xD;
&#xD;
          3. Women of child-bearing potential who are pregnant or breastfeeding because of the&#xD;
             potentially dangerous effects of the preparative chemotherapy on the fetus or infant.&#xD;
&#xD;
          4. Suffered from other malignant tumors (except the cure of basal cell carcinoma or&#xD;
             uterine cervical carcinoma in situ) previously.&#xD;
&#xD;
          5. Patients with significantly lower heart, liver, lung, kidney and bone marrow function.&#xD;
&#xD;
          6. Severe, uncontrolled medical conditions and infections.&#xD;
&#xD;
          7. At the same time using other test drugs or in other clinical trials.&#xD;
&#xD;
          8. Refusal or inability to sign informed consent to participate in the trial.&#xD;
&#xD;
          9. Other treatment contraindications.&#xD;
&#xD;
         10. Emotional disturbance or mental illness, no civil capacity or limited capacity for&#xD;
             civil conduct.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Haiqiang Mai, Ph.D</last_name>
    <phone>86-20-87343380</phone>
    <email>maihq@sysucc.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Linquan Tang, Ph.D</last_name>
    <phone>86-20-87343380</phone>
    <email>tanglq@sysucc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sun Yat-sen Universitty Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hai-Qiang Mai, MD,PhD</last_name>
      <phone>+862087343643</phone>
      <email>maihq@sysucc.org.cn</email>
    </contact>
    <investigator>
      <last_name>Hai-Qiang Mai, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <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>
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    <citation>Ribassin-Majed L, Marguet S, Lee AWM, Ng WT, Ma J, Chan ATC, Huang PY, Zhu G, Chua DTT, Chen Y, Mai HQ, Kwong DLW, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Bourhis J, Pignon JP, Blanchard P. What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis. J Clin Oncol. 2017 Feb 10;35(5):498-505. doi: 10.1200/JCO.2016.67.4119. Epub 2016 Dec 5.</citation>
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    <citation>Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, Chan AT, Huang PY, Benhamou E, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Zhang L, Hui EP, Lu TX, Bourhis J, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015 Jun;16(6):645-55. doi: 10.1016/S1470-2045(15)70126-9. Epub 2015 May 6.</citation>
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    <citation>Bossi P, Orlandi E, Bergamini C, Locati LD, Granata R, Mirabile A, Parolini D, Franceschini M, Fallai C, Olmi P, Quattrone P, Potepan P, Gloghini A, Miceli R, Mattana F, Scaramellini G, Licitra L. Docetaxel, cisplatin and 5-fluorouracil-based induction chemotherapy followed by intensity-modulated radiotherapy concurrent with cisplatin in locally advanced EBV-related nasopharyngeal cancer. Ann Oncol. 2011 Nov;22(11):2495-2500. doi: 10.1093/annonc/mdq783. Epub 2011 Mar 11.</citation>
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    <citation>Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.</citation>
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    <citation>Chan AT, Lo YM, Zee B, Chan LY, Ma BB, Leung SF, Mo F, Lai M, Ho S, Huang DP, Johnson PJ. Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst. 2002 Nov 6;94(21):1614-9. doi: 10.1093/jnci/94.21.1614.</citation>
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    <citation>Hou X, Zhao C, Guo Y, Han F, Lu LX, Wu SX, Li S, Huang PY, Huang H, Zhang L. Different clinical significance of pre- and post-treatment plasma Epstein-Barr virus DNA load in nasopharyngeal carcinoma treated with radiotherapy. Clin Oncol (R Coll Radiol). 2011 Mar;23(2):128-33. doi: 10.1016/j.clon.2010.09.001. Epub 2010 Oct 12.</citation>
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    <citation>Lin JC, Wang WY, Chen KY, Wei YH, Liang WM, Jan JS, Jiang RS. Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med. 2004 Jun 10;350(24):2461-70. doi: 10.1056/NEJMoa032260.</citation>
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    <citation>Huang CL, Sun ZQ, Guo R, Liu X, Mao YP, Peng H, Tian L, Lin AH, Li L, Shao JY, Sun Y, Ma J, Tang LL. Plasma Epstein-Barr Virus DNA Load After Induction Chemotherapy Predicts Outcome in Locoregionally Advanced Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):355-361. doi: 10.1016/j.ijrobp.2019.01.007. Epub 2019 Jan 23.</citation>
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    <citation>Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, Iyer H, Arvind AS. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs. 2009 Jan-Feb;1(1):41-8. doi: 10.4161/mabs.1.1.7509.</citation>
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    <citation>You R, Sun R, Hua YJ, Li CF, Li JB, Zou X, Yang Q, Liu YP, Zhang YN, Yu T, Cao JY, Zhang MX, Jiang R, Mo HY, Guo L, Cao KJ, Lin AH, Qian CN, Sun Y, Ma J, Chen MY. Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma. Int J Cancer. 2017 Sep 15;141(6):1265-1276. doi: 10.1002/ijc.30819. Epub 2017 Jun 23.</citation>
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  <verification_date>November 2021</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Hai-Qiang Mai,MD,PhD</investigator_full_name>
    <investigator_title>Deputy Director of the Department of Nasopharyngeal Carcinoma</investigator_title>
  </responsible_party>
  <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>Cisplatin</mesh_term>
    <mesh_term>Nimotuzumab</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/NCT04456322
org study id: 2020-FXY-001
nct id: NCT04456322
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker
      nimotuzumab versus radiotherapy plus cisplatin(CCRT) for nasopharyngeal carcinoma (NPC)
      patients with favorable response to induction chemotheray(IC), determining whether
      radiotherapy combined with nimotuzumab was non-inferior to CCRT and may provide new evidence
      for individualized comprehensive treatment of locoregionally advanced NPC.
Currently, NCCN (National Comprehensive Cancer Network) guidelines recommend induction
      chemotherapy combined with concurrent chemoradiotherapy as IIA level-evidenced treatment for
      locally advanced nasopharyngeal carcinoma (stage II-IVa). However, although induction
      chemotherapy combined with cisplatin based concurrent radiotherapy (CCRT) can significantly
      improve the survival of patients, the side effects during radiotherapy are more serious.

      Previous studies have demonstrated that with a cut-off point of 1500 copies/mL, NPC patients
      could be segregated into a low-risk subgroup and a high-risk subgroup. Besides, our previous
      results showed that patients with plasma Epstein-Barr virus (EBV) DNA= 0 copy/mL and complete
      response/partial response (CR/PR) after induction chemotherapy had a significantly lower risk
      of disease progression than patients with plasma EBV DNA>0 copy/mL and stable disease
      /progressive disease (SD/PD),according to Response Evaluation Criteria in Solid Tumors
      (RECIST). As for these low-risk and chemotheray sensitive patients, it can be considered to
      reduce the current standard treatment intensity without affecting the survival rate of
      patients, which reduces the side effects of patients and improve the their life qualities.

      Epidermal growth factor (EGFR) is an important therapeutic target for nasopharyngeal
      carcinoma. A retrospective study suggested that there was no significant difference in the
      3-year overall survival between NPC patients who received nimotuzumab / cetuximab plus
      radiotherapy and those who received standard CCRT. Besides, in terms of hepatorenal toxicity,
      anti-EGFR drugs showed better safety compared with traditional cisplatin chemotherapy. Up to
      now, randomized clinical trial about the application of nimotuzumab after IC is still
      limited.

      This is a phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker
      nimotuzumab versus radiotherapy plus cisplatin for NPC patients with favorable response after
      IC, determining whether radiotherapy combined with nimotuzumab was non-inferior to CCRT after
      IC and may provide new evidence for individualized comprehensive treatment of locoregionally
      advanced NPC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-Free Survival (PFS)
time frame: 2 years
description: Defined from date of randomization to date of first documentation of progression or death due to any cause
measure: Overall Survival (OS)
time frame: 2 years
description: Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up.
measure: Locoregional Relapse-Free Survival (LRFS)
time frame: 2 years
description: Defined from date of randomization to date of first documentation of locoregional relapse or the date of death from any cause or until the date of the last follow-up visit
measure: Distant Metastasis-Free Survival (DMFS)
time frame: 2 years
description: Defined from date of randomization to date of first documentation of distant metastases or the date of death from any cause or until the date of the last follow-up visit
measure: Objective Response Rate (ORR)
time frame: Three months after the completion of the CCRT with or without Nimotuzumab treatment
description: An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI)
measure: Incidence rate of adverse events (AEs)
time frame: 2 years
description: Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.
measure: Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes
time frame: 2 years
description: Pre-treatment EGFR expression level and EGFR Gene Copy Number is evaluated by means of immunohistochemical testing and fluorescent in situ hybridization (FISH), respectively.
measure: Change of QoL
time frame: 1 years
description: QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy
measure: Change of EORTC quality of life questionnaire(QLQ) Head and Neck score
time frame: 1 years
description: QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva,coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.All of the scores mentioned above were assessed at the below time point:before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy
measure: Plasma EBV DNA copy number
time frame: 2 years
description: Plasma EBV DNA copy number in both arms was assessed by Quantitative real time polymerase chain reaction(qRT-PCR) at pretreatment, after two cycle induction chemotherapy, during CCRT and follow up time . The predictive value of plasma EBV DNA copy number was assessed by survival analysis.
arm group label: RT plus Nimotuzumab
arm group type: Experimental
description: Patients with pretreatment plasma EBV DNA<1500 copy/ml and up to CR/PR according to RECIST and the EBV DNA reduced to undectable(0 copy/mL ) after two cycle induction chemotherapy ( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-FU 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)
arm group label: RT plus Cisplatin
arm group type: Active Comparator
description: Patients with pretreatment plasma EBV DNA<1500 copy/ml and up to CR/PR according to RECIST and the EBV DNA reduced to undectable(0 copy/mL ) after two cycle induction chemotherapy( TPF :Paclitaxel liposome135mg/m2 d1+DDP 25mg/m2 d1-d3+ 5-FU 750mg /m2/day civ120h, every 3 weeks for 2 courses) will have concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy) )
intervention type: Drug
intervention name: RT plus Nimotuzumab
description: Nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)
arm group label: RT plus Nimotuzumab
intervention type: Drug
intervention name: RT plus Cisplatin
description: concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy )
arm group label: RT plus Cisplatin
other name: Cisplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Haiqiang Mai, Ph.D
phone: 86-20-87343380
email: maihq@sysucc.org.cn
last name: Linquan Tang, Ph.D
phone: 86-20-87343380
email: tanglq@sysucc.org.cn
facility: 
status: Recruiting
contact: 
investigator: 
country: China
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responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Hai-Qiang Mai,MD,PhD
investigator title: Deputy Director of the Department of Nasopharyngeal Carcinoma
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma
mesh term: Cisplatin
mesh term: Nimotuzumab