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Toripalimab Combined With Chemoradiotherapy in Patients With Locoregionally-advanced Nasopharyngeal Carcinoma

Primary Purpose

Nasopharyngeal Neoplasms

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Toripalimab
Albumin-bound Paclitaxel
Cisplatin
intensity-modulated radiotherapy
Sponsored by
First People's Hospital of Foshan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Neoplasms

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Only the patients meeting all the following criteria can be eligible to participate in the trial:

    1. Fully understand this study and voluntarily sign the informed consent form (ICF); have good compliance;
    2. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III ;
    3. locoregionally advanced nasopharyngeal carcinoma (LANPC)(T3-4N0-1M0/T1-4N2-3M0);
    4. Age 18 to 70 years;
    5. ECOG PS 0-1;
    6. The laboratory examination results before enrollment must meet the following standards:

      1. Neutrophils ≥1.5 × 109 / L;
      2. Platelets ≥100 × 109 / L;
      3. Hemoglobin ≥90g / L (no infusion of concentrated red blood cells within 4 weeks);
      4. Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 60 mL / min;
      5. Total serum bilirubin ≤ 1.5 × ULN;
      6. AST and ALT ≤ 2.5 × ULN;
      7. The ULN of coagulation parameters APTT is not extended for more than 10 seconds, and the ULN of PT is not extended for more than 3 seconds;
    7. Women of childbearing age must confirm that the serum pregnancy test is negative and agree to use effective contraception during drug use and within 1 year after the last dose;Men whose female partners have the ability to become pregnant must agree to use reliable contraception within 1 year from the screening visit to the last Toripalimab administration.

Exclusion Criteria:

  1. Women of child-bearing potential are pregnant or breastfeeding ;
  2. Have known allergy to large molecule protein products or any compound of Toripalimab;
  3. Central nervous system metastases with clinical symptoms accompanied by cerebral edema, requiring hormone intervention, or progression of brain metastases;
  4. Prior malignancy within 5 years, except carcinoma in situ of the cervix, adequately treated basal cell carcinoma of the skin and papillary thyroid carcinoma;
  5. Received any of the following treatments:

    1. Patients who have been treated with inhibitors of immune regulation (CTLA-4, PD-1, PD-L1, etc.);
    2. Received any research drug within 4 weeks before the first administration of the drug;
    3. Join another clinical study at the same time, unless it is an observational (non-interventional) study or intervention study during follow-up;
    4. Within 28 days before signing the informed consent, received an equivalent dose of >10 mg prednisone/day or other immunosuppressive therapy, and a systemic hormone dose of ≤10 mg prednisone/day or inhaled/topical corticosteroids;
    5. Have been vaccinated with anti-tumor vaccines or have been vaccinated with live vaccines within 4 weeks before the first administration of study drugs;
    6. Have undergone major surgery or severe trauma within 4 weeks before the first administration of study drugs;
  6. Uncontrolled clinical symptoms or diseases of the heart, such as: (1) Heart failure above NYHA level II (2) Unstable angina (3) Myocardial infarction occurred within 1 year (4) Clinically supraventricular or Patients with ventricular arrhythmias requiring clinical intervention;
  7. Serious infections (CTCAE>2) within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, and infection comorbidities that require hospitalization; baseline chest imaging examinations suggest active lung inflammation . The symptoms and signs of infection exist within 2 weeks before the first dose or require oral or intravenous antibiotic use (excluding prophylactic antibiotic use);
  8. Have a history of interstitial lung disease and non-infectious pneumonia;
  9. Have active tuberculosis infection, or have a history of active tuberculosis infection within 1 year before enrollment, or have active tuberculosis infection one year ago but have not been formally treated;
  10. Have active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to These diseases and syndromes); Autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type I diabetes with stabilized doses of insulin; but excluding vitiligo or cured childhood asthma/allergy who do not require any intervention in adults;
  11. A history of HIV infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation and bone marrow transplantation;
  12. Have active hepatitis HBsAg positive and HBV DNA ≥2000IU/ml or 1000 copies/ml, hepatitis C (hepatitis C antibody positive, and HCV-RNA is higher than the detection limit);
  13. Known history of psychotropic substance abuse, alcoholism and drug abuse;
  14. Any other disease or condition of clinical significance that the investigator believes may affect protocol compliance, or affect the signing of an ICF, or is not suitable for participation in this clinical trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Toripalimab+induction chemotherapy +CCRT

    induction chemotherapy +CCRT

    Arm 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

    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 .

    Outcomes

    Primary Outcome Measures

    Adverse events
    Incidence of adverse events as assessed by CTCAE v5.0

    Secondary Outcome Measures

    Overall survival (OS)
    calculated from randomization to the date of death from any cause.
    Distant failure-free survival (DFFS)
    calculated from randomization to the date of first distant metastasis.
    Locoregional failure-free survival (LRFFS)
    calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence
    Overall response rate (ORR)and Complete response rate(CR)
    Defined as percentage of participants achieving complete response (CR) and partial response (PR) according to the RECIST 1.1.
    Quality of life (QoL)
    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.

    Full Information

    First Posted
    June 19, 2020
    Last Updated
    June 23, 2020
    Sponsor
    First People's Hospital of Foshan
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04446663
    Brief Title
    Toripalimab Combined With Chemoradiotherapy in Patients With Locoregionally-advanced Nasopharyngeal Carcinoma
    Official Title
    Toripalimab Combined With Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma: an Open-label, Parallel Controlled, Phase IIa Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2020
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 15, 2020 (Anticipated)
    Primary Completion Date
    December 15, 2023 (Anticipated)
    Study Completion Date
    December 15, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    First People's Hospital of Foshan

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Nasopharyngeal Neoplasms

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Toripalimab+induction chemotherapy +CCRT
    Arm Type
    Experimental
    Arm 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 Title
    induction chemotherapy +CCRT
    Arm Type
    Active Comparator
    Arm 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(s)
    Toripalimab
    Other Intervention Name(s)
    JS001
    Intervention Description
    Toripalimab 240mg ivdrip, every 3 weeks for 6 cycles, with 3 cycles combined with induction chemotherapy, 3 cycles combined with concurrent chemoradiotherapy
    Intervention Type
    Drug
    Intervention Name(s)
    Albumin-bound Paclitaxel
    Intervention Description
    Albumin-bound Paclitaxel 260 mg/m2, d1 of every cycle, every 3 weeks for 3 cycles before radiotherapy
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin
    Other Intervention Name(s)
    DDP
    Intervention 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
    Intervention Type
    Radiation
    Intervention Name(s)
    intensity-modulated radiotherapy
    Other Intervention Name(s)
    IMRT
    Intervention Description
    Definitive IMRT of ≥66 Gy will be given .
    Primary Outcome Measure Information:
    Title
    Adverse events
    Description
    Incidence of adverse events as assessed by CTCAE v5.0
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Overall survival (OS)
    Description
    calculated from randomization to the date of death from any cause.
    Time Frame
    3 years
    Title
    Distant failure-free survival (DFFS)
    Description
    calculated from randomization to the date of first distant metastasis.
    Time Frame
    3 years
    Title
    Locoregional failure-free survival (LRFFS)
    Description
    calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence
    Time Frame
    3 years
    Title
    Overall response rate (ORR)and Complete response rate(CR)
    Description
    Defined as percentage of participants achieving complete response (CR) and partial response (PR) according to the RECIST 1.1.
    Time Frame
    2 years
    Title
    Quality of life (QoL)
    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.
    Time Frame
    3 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Only the patients meeting all the following criteria can be eligible to participate in the trial: Fully understand this study and voluntarily sign the informed consent form (ICF); have good compliance; Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III ; locoregionally advanced nasopharyngeal carcinoma (LANPC)(T3-4N0-1M0/T1-4N2-3M0); Age 18 to 70 years; ECOG PS 0-1; The laboratory examination results before enrollment must meet the following standards: Neutrophils ≥1.5 × 109 / L; Platelets ≥100 × 109 / L; Hemoglobin ≥90g / L (no infusion of concentrated red blood cells within 4 weeks); Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 60 mL / min; Total serum bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; The ULN of coagulation parameters APTT is not extended for more than 10 seconds, and the ULN of PT is not extended for more than 3 seconds; Women of childbearing age must confirm that the serum pregnancy test is negative and agree to use effective contraception during drug use and within 1 year after the last dose;Men whose female partners have the ability to become pregnant must agree to use reliable contraception within 1 year from the screening visit to the last Toripalimab administration. Exclusion Criteria: Women of child-bearing potential are pregnant or breastfeeding ; Have known allergy to large molecule protein products or any compound of Toripalimab; Central nervous system metastases with clinical symptoms accompanied by cerebral edema, requiring hormone intervention, or progression of brain metastases; Prior malignancy within 5 years, except carcinoma in situ of the cervix, adequately treated basal cell carcinoma of the skin and papillary thyroid carcinoma; Received any of the following treatments: Patients who have been treated with inhibitors of immune regulation (CTLA-4, PD-1, PD-L1, etc.); Received any research drug within 4 weeks before the first administration of the drug; Join another clinical study at the same time, unless it is an observational (non-interventional) study or intervention study during follow-up; Within 28 days before signing the informed consent, received an equivalent dose of >10 mg prednisone/day or other immunosuppressive therapy, and a systemic hormone dose of ≤10 mg prednisone/day or inhaled/topical corticosteroids; Have been vaccinated with anti-tumor vaccines or have been vaccinated with live vaccines within 4 weeks before the first administration of study drugs; Have undergone major surgery or severe trauma within 4 weeks before the first administration of study drugs; Uncontrolled clinical symptoms or diseases of the heart, such as: (1) Heart failure above NYHA level II (2) Unstable angina (3) Myocardial infarction occurred within 1 year (4) Clinically supraventricular or Patients with ventricular arrhythmias requiring clinical intervention; Serious infections (CTCAE>2) within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, and infection comorbidities that require hospitalization; baseline chest imaging examinations suggest active lung inflammation . The symptoms and signs of infection exist within 2 weeks before the first dose or require oral or intravenous antibiotic use (excluding prophylactic antibiotic use); Have a history of interstitial lung disease and non-infectious pneumonia; Have active tuberculosis infection, or have a history of active tuberculosis infection within 1 year before enrollment, or have active tuberculosis infection one year ago but have not been formally treated; Have active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to These diseases and syndromes); Autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type I diabetes with stabilized doses of insulin; but excluding vitiligo or cured childhood asthma/allergy who do not require any intervention in adults; A history of HIV infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation and bone marrow transplantation; Have active hepatitis HBsAg positive and HBV DNA ≥2000IU/ml or 1000 copies/ml, hepatitis C (hepatitis C antibody positive, and HCV-RNA is higher than the detection limit); Known history of psychotropic substance abuse, alcoholism and drug abuse; Any other disease or condition of clinical significance that the investigator believes may affect protocol compliance, or affect the signing of an ICF, or is not suitable for participation in this clinical trial.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Guo Yi Zhang, Doctor
    Phone
    +86-0757-83162735
    Email
    guoyizhff@163.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Toripalimab Combined With Chemoradiotherapy in Patients With Locoregionally-advanced Nasopharyngeal Carcinoma

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