Clinical trial NCT04446663: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Nasopharyngeal Neoplasms
Lead sponsor: First People's Hospital of Foshan
Sponsor class: OTHER
First posted: 2020-06-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 3 years
measure: Distant failure-free survival (DFFS)
timeFrame: 3 years
measure: Locoregional failure-free survival (LRFFS)
timeFrame: 3 years
measure: Overall response rate （ORR）and Complete response rate（CR）
timeFrame: 2 years
measure: Quality of life (QoL)
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
References: