<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/NCT04446663</url>
  </required_header>
  <id_info>
    <org_study_id>JS001-ISS-CO185</org_study_id>
    <nct_id>NCT04446663</nct_id>
  </id_info>
  <brief_title>Toripalimab Combined With Chemoradiotherapy in Patients With Locoregionally-advanced Nasopharyngeal Carcinoma</brief_title>
  <official_title>Toripalimab Combined With Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma: an Open-label, Parallel Controlled, Phase IIa Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First People's Hospital of Foshan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First People's Hospital of Foshan</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 an open-label, parallel controlled, phase IIa exploratory study that evaluates the&#xD;
      efficacy and safety of Toripalimab (PD-1 Antibody) combined with induction chemotherapy&#xD;
      （Albumin-bound paclitaxel and cisplatin ）and concurrent chemoradiotherapy in the treatment of&#xD;
      nasopharyngeal carcinoma and explores the biomarkers that can predict the efficacy and&#xD;
      toxicity of the treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">July 15, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2023</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>Adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>Incidence of adverse events as assessed by CTCAE v5.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>3 years</time_frame>
    <description>calculated from randomization to the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant failure-free survival (DFFS)</measure>
    <time_frame>3 years</time_frame>
    <description>calculated from randomization to the date of first distant metastasis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Locoregional failure-free survival (LRFFS)</measure>
    <time_frame>3 years</time_frame>
    <description>calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate （ORR）and Complete response rate（CR）</measure>
    <time_frame>2 years</time_frame>
    <description>Defined as percentage of participants achieving complete response (CR) and partial response (PR) according to the RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QoL)</measure>
    <time_frame>3 years</time_frame>
    <description>The change of QoL from randomization to 12 months after chemoradiation. The European Organization for Research and Treatment of Cancer quality of life questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual: 1. Estimate the average of the questions that contribute to the scale; this is the raw score. 2. Use a linear transformation to standardise the raw score, so that scores range from 0 to 100. Thus, a high score for a functional scale represents a high level of functioning, a high score for the global health status represents a high QoL, but a high score for a symptom scale represents a high level of problems.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Nasopharyngeal Neoplasms</condition>
  <arm_group>
    <arm_group_label>Toripalimab+induction chemotherapy +CCRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive induction chemotherapy with Albumin-bound paclitaxel (260 mg/m2, d1 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiotherapy.&#xD;
Then patients will receive definitive intensity-modulated radiotherapy (IMRT) of ≥66 Gy（2-2.2Gy/fx）.Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT .&#xD;
Toripalimab 240mg will be given every 3 weeks for 6 cycles, started on day 1 of induction chemotherapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>induction chemotherapy +CCRT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive induction chemotherapy with Albumin-bound paclitaxel (260 mg/m2, d1 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiotherapy.&#xD;
Then patients will receive definitive intensity-modulated radiotherapy (IMRT) of ≥66 Gy（2-2.2Gy/fx）.Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT .</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>Toripalimab 240mg ivdrip, every 3 weeks for 6 cycles, with 3 cycles combined with induction chemotherapy, 3 cycles combined with concurrent chemoradiotherapy</description>
    <arm_group_label>Toripalimab+induction chemotherapy +CCRT</arm_group_label>
    <other_name>JS001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Albumin-bound Paclitaxel</intervention_name>
    <description>Albumin-bound Paclitaxel 260 mg/m2, d1 of every cycle, every 3 weeks for 3 cycles before radiotherapy</description>
    <arm_group_label>Toripalimab+induction chemotherapy +CCRT</arm_group_label>
    <arm_group_label>induction chemotherapy +CCRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiotherapy Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiotherapy</description>
    <arm_group_label>Toripalimab+induction chemotherapy +CCRT</arm_group_label>
    <arm_group_label>induction chemotherapy +CCRT</arm_group_label>
    <other_name>DDP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>intensity-modulated radiotherapy</intervention_name>
    <description>Definitive IMRT of ≥66 Gy will be given .</description>
    <arm_group_label>Toripalimab+induction chemotherapy +CCRT</arm_group_label>
    <arm_group_label>induction chemotherapy +CCRT</arm_group_label>
    <other_name>IMRT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Only the patients meeting all the following criteria can be eligible to participate in&#xD;
             the trial:&#xD;
&#xD;
               1. Fully understand this study and voluntarily sign the informed consent form (ICF);&#xD;
                  have good compliance;&#xD;
&#xD;
               2. Patients with newly histologically confirmed non-keratinizing nasopharyngeal&#xD;
                  carcinoma, including WHO II or III ;&#xD;
&#xD;
               3. locoregionally advanced nasopharyngeal carcinoma (LANPC)（T3-4N0-1M0/T1-4N2-3M0）;&#xD;
&#xD;
               4. Age 18 to 70 years;&#xD;
&#xD;
               5. ECOG PS 0-1;&#xD;
&#xD;
               6. The laboratory examination results before enrollment must meet the following&#xD;
                  standards:&#xD;
&#xD;
                    1. Neutrophils ≥1.5 × 109 / L;&#xD;
&#xD;
                    2. Platelets ≥100 × 109 / L;&#xD;
&#xD;
                    3. Hemoglobin ≥90g / L (no infusion of concentrated red blood cells within 4&#xD;
                       weeks);&#xD;
&#xD;
                    4. Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 60 mL / min;&#xD;
&#xD;
                    5. Total serum bilirubin ≤ 1.5 × ULN;&#xD;
&#xD;
                    6. AST and ALT ≤ 2.5 × ULN;&#xD;
&#xD;
                    7. The ULN of coagulation parameters APTT is not extended for more than 10&#xD;
                       seconds, and the ULN of PT is not extended for more than 3 seconds;&#xD;
&#xD;
               7. Women of childbearing age must confirm that the serum pregnancy test is negative&#xD;
                  and agree to use effective contraception during drug use and within 1 year after&#xD;
                  the last dose；Men whose female partners have the ability to become pregnant must&#xD;
                  agree to use reliable contraception within 1 year from the screening visit to the&#xD;
                  last Toripalimab administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women of child-bearing potential are pregnant or breastfeeding ;&#xD;
&#xD;
          2. Have known allergy to large molecule protein products or any compound of Toripalimab;&#xD;
&#xD;
          3. Central nervous system metastases with clinical symptoms accompanied by cerebral&#xD;
             edema, requiring hormone intervention, or progression of brain metastases;&#xD;
&#xD;
          4. Prior malignancy within 5 years, except carcinoma in situ of the cervix, adequately&#xD;
             treated basal cell carcinoma of the skin and papillary thyroid carcinoma;&#xD;
&#xD;
          5. Received any of the following treatments:&#xD;
&#xD;
               1. Patients who have been treated with inhibitors of immune regulation (CTLA-4,&#xD;
                  PD-1, PD-L1, etc.);&#xD;
&#xD;
               2. Received any research drug within 4 weeks before the first administration of the&#xD;
                  drug;&#xD;
&#xD;
               3. Join another clinical study at the same time, unless it is an observational&#xD;
                  (non-interventional) study or intervention study during follow-up;&#xD;
&#xD;
               4. Within 28 days before signing the informed consent, received an equivalent dose&#xD;
                  of &gt;10 mg prednisone/day or other immunosuppressive therapy, and a systemic&#xD;
                  hormone dose of ≤10 mg prednisone/day or inhaled/topical corticosteroids;&#xD;
&#xD;
               5. Have been vaccinated with anti-tumor vaccines or have been vaccinated with live&#xD;
                  vaccines within 4 weeks before the first administration of study drugs;&#xD;
&#xD;
               6. Have undergone major surgery or severe trauma within 4 weeks before the first&#xD;
                  administration of study drugs;&#xD;
&#xD;
          6. Uncontrolled clinical symptoms or diseases of the heart, such as: (1) Heart failure&#xD;
             above NYHA level II (2) Unstable angina (3) Myocardial infarction occurred within 1&#xD;
             year (4) Clinically supraventricular or Patients with ventricular arrhythmias&#xD;
             requiring clinical intervention;&#xD;
&#xD;
          7. Serious infections (CTCAE&gt;2) within 4 weeks before the first use of the study drug,&#xD;
             such as severe pneumonia, bacteremia, and infection comorbidities that require&#xD;
             hospitalization; baseline chest imaging examinations suggest active lung inflammation&#xD;
             . The symptoms and signs of infection exist within 2 weeks before the first dose or&#xD;
             require oral or intravenous antibiotic use (excluding prophylactic antibiotic use);&#xD;
&#xD;
          8. Have a history of interstitial lung disease and non-infectious pneumonia;&#xD;
&#xD;
          9. Have active tuberculosis infection, or have a history of active tuberculosis infection&#xD;
             within 1 year before enrollment, or have active tuberculosis infection one year ago&#xD;
             but have not been formally treated;&#xD;
&#xD;
         10. Have active autoimmune diseases or a history of autoimmune diseases (such as&#xD;
             interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis,&#xD;
             nephritis, hyperthyroidism, hypothyroidism, including but not limited to These&#xD;
             diseases and syndromes); Autoimmune-mediated hypothyroidism treated with stable doses&#xD;
             of thyroid replacement hormone; Type I diabetes with stabilized doses of insulin; but&#xD;
             excluding vitiligo or cured childhood asthma/allergy who do not require any&#xD;
             intervention in adults;&#xD;
&#xD;
         11. A history of HIV infection, or other acquired, congenital immunodeficiency diseases,&#xD;
             or a history of organ transplantation and bone marrow transplantation;&#xD;
&#xD;
         12. Have active hepatitis HBsAg positive and HBV DNA ≥2000IU/ml or 1000 copies/ml,&#xD;
             hepatitis C (hepatitis C antibody positive, and HCV-RNA is higher than the detection&#xD;
             limit);&#xD;
&#xD;
         13. Known history of psychotropic substance abuse, alcoholism and drug abuse;&#xD;
&#xD;
         14. Any other disease or condition of clinical significance that the investigator believes&#xD;
             may affect protocol compliance, or affect the signing of an ICF, or is not suitable&#xD;
             for participation in this clinical trial.&#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>Guo Yi Zhang, Doctor</last_name>
    <phone>+86-0757-83162735</phone>
    <email>guoyizhff@163.com</email>
  </overall_contact>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>First People's Hospital of Foshan</investigator_affiliation>
    <investigator_full_name>Guo-Yi Zhang</investigator_full_name>
    <investigator_title>Chief Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04446663
org study id: JS001-ISS-CO185
nct id: NCT04446663
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is an open-label, parallel controlled, phase IIa exploratory study that evaluates the
      efficacy and safety of Toripalimab (PD-1 Antibody) combined with induction chemotherapy
      （Albumin-bound paclitaxel and cisplatin ）and concurrent chemoradiotherapy in the treatment of
      nasopharyngeal carcinoma and explores the biomarkers that can predict the efficacy and
      toxicity of the treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events
time frame: 2 years
description: Incidence of adverse events as assessed by CTCAE v5.0
measure: Overall survival (OS)
time frame: 3 years
description: calculated from randomization to the date of death from any cause.
measure: Distant failure-free survival (DFFS)
time frame: 3 years
description: calculated from randomization to the date of first distant metastasis.
measure: Locoregional failure-free survival (LRFFS)
time frame: 3 years
description: calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence
measure: Overall response rate （ORR）and Complete response rate（CR）
time frame: 2 years
description: Defined as percentage of participants achieving complete response (CR) and partial response (PR) according to the RECIST 1.1.
measure: Quality of life (QoL)
time frame: 3 years
description: The change of QoL from randomization to 12 months after chemoradiation. The European Organization for Research and Treatment of Cancer quality of life questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual: 1. Estimate the average of the questions that contribute to the scale; this is the raw score. 2. Use a linear transformation to standardise the raw score, so that scores range from 0 to 100. Thus, a high score for a functional scale represents a high level of functioning, a high score for the global health status represents a high QoL, but a high score for a symptom scale represents a high level of problems.
arm group label: Toripalimab+induction chemotherapy +CCRT
arm group type: Experimental
description: Patients will receive induction chemotherapy with Albumin-bound paclitaxel (260 mg/m2, d1 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiotherapy.
Then patients will receive definitive intensity-modulated radiotherapy (IMRT) of ≥66 Gy（2-2.2Gy/fx）.Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT .
Toripalimab 240mg will be given every 3 weeks for 6 cycles, started on day 1 of induction chemotherapy
arm group label: induction chemotherapy +CCRT
arm group type: Active Comparator
description: Patients will receive induction chemotherapy with Albumin-bound paclitaxel (260 mg/m2, d1 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiotherapy.
Then patients will receive definitive intensity-modulated radiotherapy (IMRT) of ≥66 Gy（2-2.2Gy/fx）.Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT .
intervention type: Drug
intervention name: Toripalimab
description: Toripalimab 240mg ivdrip, every 3 weeks for 6 cycles, with 3 cycles combined with induction chemotherapy, 3 cycles combined with concurrent chemoradiotherapy
arm group label: Toripalimab+induction chemotherapy +CCRT
other name: JS001
intervention type: Drug
intervention name: Albumin-bound Paclitaxel
description: Albumin-bound Paclitaxel 260 mg/m2, d1 of every cycle, every 3 weeks for 3 cycles before radiotherapy
arm group label: Toripalimab+induction chemotherapy +CCRT
arm group label: induction chemotherapy +CCRT
intervention type: Drug
intervention name: Cisplatin
description: Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiotherapy Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiotherapy
arm group label: Toripalimab+induction chemotherapy +CCRT
arm group label: induction chemotherapy +CCRT
other name: DDP
intervention type: Radiation
intervention name: intensity-modulated radiotherapy
description: Definitive IMRT of ≥66 Gy will be given .
arm group label: Toripalimab+induction chemotherapy +CCRT
arm group label: induction chemotherapy +CCRT
other name: IMRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Guo Yi Zhang, Doctor
phone: +86-0757-83162735
email: guoyizhff@163.com
responsible party type: Principal Investigator
investigator affiliation: First People's Hospital of Foshan
investigator full name: Guo-Yi Zhang
investigator title: Chief Physician
mesh term: Nasopharyngeal Carcinoma
mesh term: Nasopharyngeal Neoplasms
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
sharing ipd: No