Toripalimab, Induction Chemotherapy, Radiation Therapy With Omega-3 for Locally Advanced Nasopharyngeal Carcinoma

After being informed about the study and potential risks, all patients giving written informedconsent will undergo a 1-week screening period to determine eligibility for study entry. In week 0, eligible patients will be enrolled in a clinical study on the combination of Toripalimab, induction chemotherapy, sequential radiotherapy, and OMEGA-3 for the treatment of locally advanced nasopharyngeal carcinoma. Induction chemotherapy stage: Toripalimab 240mg d1, paclitaxel (albumin bound) 260mg/m2 d1, cisplatin 80mg/m2 d2 Q3W X 3 cycles. Radiotherapy stage: IMRT+Toripalimab 240mg Q3W X 3 cycles+Omega-3 (6 pills qd during radiotherapy). IMRT：GTVnx 69.96Gy，GTVnd 69.96Gy，CTV1 60Gy，CTV2 54Gy。 Maintenance treatment: Toripalimab 240mg Q3W X 6 cycles.

Inclusion criteria

• Written informed consent can be provided, and understanding and compliance with research requirements and evaluation schedules are required.
• On the date of signing the informed consent form, the age range is between 18 and 65 years old (or the legal age specified by local laws).
• Pathological diagnosis is non keratinizing carcinoma of the nasopharynx (differentiated or undifferentiated, i.e. WHO classification II or III).
• Clinical staging is anyTN2-3M0 or T4N1M0 (AJCC8th/UICC staging).
• ECOG score is 0-1 points.
• Hemoglobin (HGB) ≥ 90g/L, white blood cell (WBC) ≥ 4.0 × 109/L, platelet (PLT) ≥ 100 × 109/L.
• Liver function: ALT and AST<2.5 times the upper limit of normal (ULN), total bilirubin<2.0 × UL, serum albumin ≥ 28g/L.
• Renal function: Serum creatinine<1.5 × ULN or creatinine clearance rate (CrCl) calculated value ≥ 60mL/min (Cockcroft Gault formula).
• Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously. If FT3 and FT4 levels are normal, they can be included in the group).
• The international normalized ratio (INR) and activated partial thromboplastin time (APTT) are ≤ 1.5 × ULN (unless the subject is receiving anticoagulant treatment and the coagulation parameters (PT/INR and APTT) are within the expected range of anticoagulant treatment at the time of screening).

Exclusion criteria

• Nasopharyngeal cancer patients with recurrence and distant metastasis.
• Pathology shows keratinized squamous cell carcinoma (WHO classification type I).
• Patients who have undergone radiotherapy or systemic chemotherapy before.
• Pregnant or lactating women who are in the reproductive period and have not taken effective contraceptive measures.
• HIV positive.
• Have suffered from other malignant tumors (except for cured basal cell carcinoma or cervical carcinoma in situ).
• Patients who have been treated with immune checkpoint inhibitors (CTLA-4, PD-1, PD-L1, etc.).
• Patients with immunodeficiency diseases and a history of organ transplantation.
• Patients who have been treated with high-dose corticosteroids, anti-cancer monoclonal antibodies, or other immunosuppressive agents within 4 weeks.
• Patients with significantly impaired heart, liver, lung, kidney, and bone marrow function.
• Simultaneously using other investigational drugs or in other clinical trials.
• Refusal or inability to sign the informed consent form for participation in the trial.
• Individuals with personality or mental disorders, without civil capacity or with limited civil capacity.
• hepatitis B B surface antigen (HBsAg) is positive and the peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) is ≥ 1000 cps/ml.
• Patients with positive HCV antibody test results are only eligible for this study if their HCV RNA polymerase chain reaction test results are negative.
• Patients who have experienced any bleeding events with a severity rating of 3 or above in CTCAE5.0 within the first 4 weeks of screening and are deemed to have a high risk of bleeding by the researchers.
• If there have been any arterial/venous thrombotic events within the 6 months prior to the start of screening, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
• Patients with hypertension who cannot be reduced to the normal range through antihypertensive medication (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg); Based on the average of BP readings obtained from ≥ 2 measurements, there has been a history of hypertensive crisis or hypertensive encephalopathy.
• Past or current inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea); History of previous or existing gastrointestinal perforation and/or fistula.
• Known history of active pulmonary tuberculosis (TB). Subjects suspected of having active TB should undergo chest X-ray, sputum examination, and exclusion based on clinical symptoms and signs.
• Other serious, uncontrolled internal medical conditions and infections, or other contraindications to treatment, or any condition that researchers believe may pose a risk to receiving the study drug treatment, or interfere with the evaluation of the study drug, subject safety, or analysis of the study results.