<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/NCT04453813</url>
  </required_header>
  <id_info>
    <org_study_id>SYSUCC-MYC-2020-2101</org_study_id>
    <nct_id>NCT04453813</nct_id>
  </id_info>
  <brief_title>Toripalimab Plus Concurrent Chemo-radiotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma</brief_title>
  <official_title>A Multicenter Randomized Clinical Phase 3 Trial of Toripalimab Plus Concurrent Chemo-radiotherapy vs Concurrent Chemo-radiotherapy Alone for Unresectable Locally Recurrent Nasopharyngeal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <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>
    <collaborator>
      <agency>Fifth Affiliated Hospital, Sun Yat-Sen University</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;
      concurrent and adjuvant PD-1 treatment added to concurrent chemo-radiotherapy could further&#xD;
      decrease the rate of disease progression and improve the survival outcome of patients with&#xD;
      unresectable locally recurrent nasopharyngeal carcinoma compared with those treated with&#xD;
      concurrent chemo-radiotherapy alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Through multicenter, open-label, randomised clinical trials, patients with unresectable&#xD;
      locally recurrent nasopharyngeal carcinoma are randomized into concurrent chemo-radiotherapy&#xD;
      plus concurrent and adjuvant PD-1 treatment group and concurrent chemo-radiotherapy alone&#xD;
      group. The efficacy and safety of patients between these two groups are compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 3, 2020</start_date>
  <completion_date type="Anticipated">July 2027</completion_date>
  <primary_completion_date type="Anticipated">July 2025</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">226</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <condition>Chemotherapy</condition>
  <condition>Radiotherapy</condition>
  <condition>PD-1 Treatment</condition>
  <arm_group>
    <arm_group_label>Toripalimab plus concurrent chemo-radiotherapy arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Concurrent chemo-radiotherapy plus concurrent and adjuvant toripalimab.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Concurrent chemo-radiotherapy arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Concurrent chemo-radiotherapy alone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab plus concurrent chemo-radiotherapy</intervention_name>
    <description>Toripalimab: 240 mg, intravenous injection over 60 minutes (Q3W); 2 cycles of toripalimab are concurrently used during radiotherapy and other 9 cycles of toripalimab are used after the end of radiotherapy. (A total of 11 cycles).&#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#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy</description>
    <arm_group_label>Toripalimab plus concurrent chemo-radiotherapy arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Concurrent chemo-radiotherapy</intervention_name>
    <description>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#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy</description>
    <arm_group_label>Concurrent chemo-radiotherapy arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed recurrent nasopharyngeal carcinoma.&#xD;
&#xD;
          2. The recurrence time is more than 12 months from the end of the first course of&#xD;
             radiotherapy.&#xD;
&#xD;
          3. Tumor staged as rT2-4N0-3M0，rII-IVa (according to the 8th AJCC edition).&#xD;
&#xD;
          4. Subjects must have a measurable disease by CT or MRI per RECIST 1.1 criteria.&#xD;
&#xD;
          5. Karnofsky scale (KPS)≥70.&#xD;
&#xD;
          6. Normal bone marrow function.&#xD;
&#xD;
          7. 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;
          8. Given written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Resectable nasopharyngeal diseases: rT2 (the tumour is confined in the superficial&#xD;
             parapharyngeal spacer and is more than 0.5cm from the internal carotid artery) and rT3&#xD;
             (the tumour is confined in the base wall of the sphenoid sinus and is more than 0.5cm&#xD;
             from the internal carotid artery and cavernous sinus).&#xD;
&#xD;
          2. The patients are suffering from severe nasopharyngeal necrosis, radiation induced&#xD;
             brain injury, and fibrosis of the neck et. al, who are evaluated as unsuitable for&#xD;
             secondary radiotherapy by the researchers.&#xD;
&#xD;
          3. Has known allergy to large molecule protein products or any compound of study therapy.&#xD;
&#xD;
          4. Has known subjects with other malignant tumors.&#xD;
&#xD;
          5. Has any active autoimmune disease or history of autoimmune disease.&#xD;
&#xD;
          6. Has a history of psychiatric substance abuse, alcoholism, or drug addiction.&#xD;
&#xD;
          7. The laboratory examination value does not meet the relevant standards within 7 days&#xD;
             before enrollment&#xD;
&#xD;
          8. Received a systematic glucocorticoid therapy within 4 weeks of the first dose of study&#xD;
             medication.&#xD;
&#xD;
          9. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with&#xD;
             adequately treated active TB with 1 year.&#xD;
&#xD;
         10. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent.&#xD;
&#xD;
         11. Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis,&#xD;
             nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy).&#xD;
             Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo,&#xD;
             psoriasis, or alopecia) will be allowed to enroll.&#xD;
&#xD;
         12. Has a known history of human immunodeficiency virus (HIV).&#xD;
&#xD;
         13. Has hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number of&#xD;
             ≥1000cps/ml or hepatitis C virus (HCV) antibody positive&#xD;
&#xD;
         14. Has received a live vaccine within 4 weeks of planned start of study therapy&#xD;
&#xD;
         15. Pregnancy or breast feeding&#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>
    <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>
    <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>
    <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>Not yet recruiting</status>
    <contact>
      <last_name>Feng Lei, MD</last_name>
      <phone>86-18933345382</phone>
      <email>13528227676@163.com</email>
    </contact>
    <investigator>
      <last_name>Feng Lei, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Fifth Affiliated Hospital of Sun Yat-sen University</name>
      <address>
        <city>Zhuhai</city>
        <state>Guangdong</state>
        <zip>519000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Zhi-Gang Liu, MD, PhD</last_name>
      <phone>86-18627585860</phone>
    </contact>
    <investigator>
      <last_name>Zhi-Gang Liu, MD, PhD</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>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_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>June 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 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>Professor, Chief Doctor</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>
  <!-- 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/NCT04453813
org study id: SYSUCC-MYC-2020-2101
nct id: NCT04453813
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
      concurrent and adjuvant PD-1 treatment added to concurrent chemo-radiotherapy could further
      decrease the rate of disease progression and improve the survival outcome of patients with
      unresectable locally recurrent nasopharyngeal carcinoma compared with those treated with
      concurrent chemo-radiotherapy alone.
Through multicenter, open-label, randomised clinical trials, patients with unresectable
      locally recurrent nasopharyngeal carcinoma are randomized into concurrent chemo-radiotherapy
      plus concurrent and adjuvant PD-1 treatment group and concurrent chemo-radiotherapy alone
      group. The efficacy and safety of patients between these two groups are 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: Toripalimab plus concurrent chemo-radiotherapy arm
arm group type: Experimental
description: Concurrent chemo-radiotherapy plus concurrent and adjuvant toripalimab.
arm group label: Concurrent chemo-radiotherapy arm
arm group type: Active Comparator
description: Concurrent chemo-radiotherapy alone.
intervention type: Drug
intervention name: Toripalimab plus concurrent chemo-radiotherapy
description: Toripalimab: 240 mg, intravenous injection over 60 minutes (Q3W); 2 cycles of toripalimab are concurrently used during radiotherapy and other 9 cycles of toripalimab are used after the end of radiotherapy. (A total of 11 cycles).
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#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy
arm group label: Toripalimab plus concurrent chemo-radiotherapy arm
intervention type: Drug
intervention name: Concurrent chemo-radiotherapy
description: 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#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy
arm group label: Concurrent chemo-radiotherapy arm
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: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ming-Yuan Chen
investigator title: Professor, Chief Doctor
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma