<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/NCT04448522</url>
  </required_header>
  <id_info>
    <org_study_id>SYSUCC-MYC-2020-1201</org_study_id>
    <nct_id>NCT04448522</nct_id>
  </id_info>
  <brief_title>Reduced vs Conventional Dosage Intensity-modulated Radiotherapy for Chemotherapy-sensitive Stage II-III Nasopharyngeal Carcinoma</brief_title>
  <official_title>A Multicenter Randomized Controlled Trial Comparing Reduced Dose With Regular Dose Intensity-modulated Radiotherapy for Chemotherapy Sensitive Stage II-III Nasopharyngeal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Centre, Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhongshan People's Hospital, Guangdong, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Yuebei People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wuzhou Red Cross Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</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>
      Through multicenter, open-label, randomised clinical trials, we intend to demonstrate that&#xD;
      radiotherapy with reduced dose could significantly reduce the incidence of radiotherapy&#xD;
      toxicities, improve the quality of life of patients while ensuring the tumor control rates&#xD;
      for NPC patients staged as II-III who are sensitive to induction chemotherapy (imaging&#xD;
      evaluation of CR/PR and EBV DNA copy number decreased to 0 copies/mL after induction&#xD;
      chemotherapy)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Through multicenter, open-label, randomised clinical trials, patients with NPC staged as&#xD;
      II-III with CR/PR according to RECIST criteria and EBV DNA decreased to 0 copies/mL after 3&#xD;
      cycles of GP induction chemotherapy will be randomized into experimental group to receive&#xD;
      IMRT of reduced dose (prescribed dose, 63.6 Gy, 2.12 Gy per fractions, 30 fractions) and&#xD;
      control group to receive IMRT of conventional dose (prescribed dose, 69.96 Gy, 2.13 Gy per&#xD;
      time, 33 fractions). Two cycles of cisplatin chemotherapy will be performed during IMRT. The&#xD;
      efficacy, toxicity, and quality of life of patients between the two groups will be compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 18, 2020</start_date>
  <completion_date type="Anticipated">August 2028</completion_date>
  <primary_completion_date type="Anticipated">August 2026</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>Progress-free survival (PFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>3 years</time_frame>
    <description>Defined as the time interval from randomization to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant Metastasis-Free Survival (DMFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Defined as the time interval from randomisation to the date of first distant metastases.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Locoregional Relapse-Free Survival (LRRFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Defined as the time from randomisation to the date of first locoregional relapse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment related acute complications</measure>
    <time_frame>up to 1 years</time_frame>
    <description>The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment related late complications</measure>
    <time_frame>up to 3 years</time_frame>
    <description>The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&amp;N35)</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&amp;N35) before treatment, during treatment, after treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">508</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <condition>Radiotherapy</condition>
  <condition>Chemotherapy</condition>
  <arm_group>
    <arm_group_label>Reduced dosage IMRT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent cheomtherapy with IMRT dosage of 63.6 Gy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional dosage IMRT group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent cheomtherapy with IMRT dosage of 69.96 Gy</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>reduced dosage IMRT</intervention_name>
    <description>Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks.&#xD;
Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks.&#xD;
IMRT: PTVnx：63.6Gy/30Fr/2.12Gy; PTVnd：63.6Gy/30Fr/2.12Gy; PTV1：54Gy/30Fr/1.8Gy; PTV2：49.2Gy/30Fr/1.64Gy</description>
    <arm_group_label>Reduced dosage IMRT group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>conventional dosage IMRT</intervention_name>
    <description>Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks.&#xD;
Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks.&#xD;
IMRT: PTVnx：69.96Gy/33Fr/2.12Gy; PTVnd：69.96Gy/33Fr/2.12Gy; PTV1：59.4Gy/33Fr/1.8Gy; PTV2：54Gy/33Fr/1.64Gy</description>
    <arm_group_label>Conventional dosage IMRT group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or&#xD;
             undifferentiated type, i.e., WHO type II or type III).&#xD;
&#xD;
          2. Staged as T1-3N1-2M0, T2-3N0M0 (stage II-III) at diagnosis (according to the 8th AJCC&#xD;
             edition).&#xD;
&#xD;
          3. Aged between 18-70 years.&#xD;
&#xD;
          4. Karnofsky scale (KPS)≥70.&#xD;
&#xD;
          5. Normal bone marrow function.&#xD;
&#xD;
          6. Evaluated as PR or CR after 3 cycles of GP induction chemotherapy.&#xD;
&#xD;
          7. EBV DNA copy number decreased to 0 copies/mL after 3 cycles of GP induction&#xD;
             chemotherapy.&#xD;
&#xD;
          8. Normal liver and kidney function:&#xD;
&#xD;
               1. total bilirubin, AST and ALT levels of no more than 2.5 times the upper normal&#xD;
                  limit;&#xD;
&#xD;
               2. creatinine clearance rate of at least 60 mL/min or creatinine of no more than 1.5&#xD;
                  times the upper normal limit.&#xD;
&#xD;
          9. Given written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed keratinized squamous cell carcinoma (WHO type I) or basal&#xD;
             squamous cell carcinoma.&#xD;
&#xD;
          2. Recurrent or metastatic nasopharyngeal carcinoma.&#xD;
&#xD;
          3. Evaluated as SD or PD after 3 cycles of GP induction chemotherapy.&#xD;
&#xD;
          4. EBV DNA copy number of more than 0 copies/mL after 3 cycles of GP induction&#xD;
             chemotherapy.&#xD;
&#xD;
          5. Pregnancy or lactation (Pregnancy tests should be considered for women in childbearing&#xD;
             age, and effective contraception should be emphasized during treatment.)&#xD;
&#xD;
          6. Other invasive malignant diseases in the past, other than cured basal cell skin&#xD;
             carcinoma, squamous cell carcinoma, cervical carcinoma in situ.&#xD;
&#xD;
          7. Primary and regional lesions have been treated with chemotherapy or surgery (except&#xD;
             diagnostic purpose)&#xD;
&#xD;
          8. Any severe disease, which may cause unacceptable risk factors or affect compliance&#xD;
             with the trial, for example, unstable heart disease requiring treatment, kidney&#xD;
             disease, chronic hepatitis, poorly controlled diabetes (fasting blood glucose &gt;&#xD;
             1.5×ULN), and mental illness.&#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>Ming-Yuan Chen, MD, PhD</last_name>
    <phone>86-20-87343624</phone>
    <email>chmingy@mail.sysu.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rui You, MD, PhD</last_name>
    <phone>86-13580439820</phone>
    <email>yourui@sysucc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ming-Yuan Chen, MD, PhD</last_name>
      <phone>86-20-8734-3361</phone>
      <email>chmingy@mail.sysu.edu.cn</email>
    </contact>
    <contact_backup>
      <last_name>Rui You, MD, PhD</last_name>
      <phone>86-13580439820</phone>
      <email>yourui@sysucc.org.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Ming-Yuan Chen, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Guangzhou Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510095</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dong-Ping Chen, MD</last_name>
      <phone>86-13302215492</phone>
      <email>chen_dpgz@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Bin Qi, PhD</last_name>
      <email>qibin020@126.com</email>
    </contact_backup>
    <investigator>
      <last_name>Dong-Ping Chen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Yuebei People's Hospital</name>
      <address>
        <city>Shaoguan</city>
        <state>Guangdong</state>
        <zip>512025</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Su-Ming Pan, MD</last_name>
      <phone>86-13826331948</phone>
    </contact>
    <contact_backup>
      <last_name>Xiang-Guo Zhang, MD</last_name>
      <phone>86-13826380511</phone>
      <email>1178906911@qq.com</email>
    </contact_backup>
    <investigator>
      <last_name>Su-Ming Pan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Zhongshan People's Hospital</name>
      <address>
        <city>Zhongshan</city>
        <state>Guangdong</state>
        <zip>528403</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Feng Lei, MD</last_name>
      <phone>86-18933345382</phone>
    </contact>
    <investigator>
      <last_name>Feng Lei, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Wuzhou Red Cross Hospital</name>
      <address>
        <city>Wuzhou</city>
        <state>Guangxi</state>
        <zip>543002</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jin-Hui Liang, MD</last_name>
      <phone>86-13878480806</phone>
    </contact>
    <investigator>
      <last_name>Jin-Hui Liang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Cancer Centre Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Melvin Lee Kiang Chua, PhD</last_name>
      <phone>65-6436-8000</phone>
      <email>melvin.chua.l.k@singhealth.com.sg</email>
    </contact>
    <investigator>
      <last_name>Melvin Lee Kiang Chua, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
    <country>Singapore</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>September 24, 2020</last_update_submitted>
  <last_update_submitted_qc>September 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Ming-Yuan Chen</investigator_full_name>
    <investigator_title>Proffessor</investigator_title>
  </responsible_party>
  <keyword>Nasopharyngeal carcinoma</keyword>
  <keyword>intensity-modulated radiotherapy</keyword>
  <keyword>chemotherapy</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>
  <!-- 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/NCT04448522
org study id: SYSUCC-MYC-2020-1201
nct id: NCT04448522
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Through multicenter, open-label, randomised clinical trials, we intend to demonstrate that
      radiotherapy with reduced dose could significantly reduce the incidence of radiotherapy
      toxicities, improve the quality of life of patients while ensuring the tumor control rates
      for NPC patients staged as II-III who are sensitive to induction chemotherapy (imaging
      evaluation of CR/PR and EBV DNA copy number decreased to 0 copies/mL after induction
      chemotherapy)
Through multicenter, open-label, randomised clinical trials, patients with NPC staged as
      II-III with CR/PR according to RECIST criteria and EBV DNA decreased to 0 copies/mL after 3
      cycles of GP induction chemotherapy will be randomized into experimental group to receive
      IMRT of reduced dose (prescribed dose, 63.6 Gy, 2.12 Gy per fractions, 30 fractions) and
      control group to receive IMRT of conventional dose (prescribed dose, 69.96 Gy, 2.13 Gy per
      time, 33 fractions). Two cycles of cisplatin chemotherapy will be performed during IMRT. The
      efficacy, toxicity, and quality of life of patients between the two groups will be compared.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progress-free survival (PFS)
time frame: 3 years
description: Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.
measure: Overall Survival (OS)
time frame: 3 years
description: Defined as the time interval from randomization to death due to any cause.
measure: Distant Metastasis-Free Survival (DMFS)
time frame: 3 years
description: Defined as the time interval from randomisation to the date of first distant metastases.
measure: Locoregional Relapse-Free Survival (LRRFS)
time frame: 3 years
description: Defined as the time from randomisation to the date of first locoregional relapse.
measure: Incidence of treatment related acute complications
time frame: up to 1 years
description: The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.
measure: Incidence of treatment related late complications
time frame: up to 3 years
description: The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)
time frame: up to 3 years
description: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
time frame: up to 3 years
description: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment.
arm group label: Reduced dosage IMRT group
arm group type: Experimental
description: 3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent cheomtherapy with IMRT dosage of 63.6 Gy
arm group label: Conventional dosage IMRT group
arm group type: Active Comparator
description: 3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent cheomtherapy with IMRT dosage of 69.96 Gy
intervention type: Radiation
intervention name: reduced dosage IMRT
description: Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks.
Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks.
IMRT: PTVnx：63.6Gy/30Fr/2.12Gy; PTVnd：63.6Gy/30Fr/2.12Gy; PTV1：54Gy/30Fr/1.8Gy; PTV2：49.2Gy/30Fr/1.64Gy
arm group label: Reduced dosage IMRT group
intervention type: Radiation
intervention name: conventional dosage IMRT
description: Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks.
Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks.
IMRT: PTVnx：69.96Gy/33Fr/2.12Gy; PTVnd：69.96Gy/33Fr/2.12Gy; PTV1：59.4Gy/33Fr/1.8Gy; PTV2：54Gy/33Fr/1.64Gy
arm group label: Conventional dosage IMRT group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ming-Yuan Chen, MD, PhD
phone: 86-20-87343624
email: chmingy@mail.sysu.edu.cn
last name: Rui You, MD, PhD
phone: 86-13580439820
email: yourui@sysucc.org.cn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: China
country: Singapore
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ming-Yuan Chen
investigator title: Proffessor
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma