Short-course Tislelizumab Combined With Chemoradiotherapy for Nasopharyngeal Carcinoma

Официальное название

Short-course Tislelizumab Combined With Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled, Multicenter, Phase 3 Non-inferiority Clinical Trial

Обзор

This trial aim to explore whether short-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 3 cycles of 400 mg q6w in the consolidation phase) yields non-inferior event-free survival compared to long-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 5 cycles of 400 mg q6w in the consolidation phase) in patients with locoregionally advanced nasopharyngeal carcinoma.

Вмешательства

• Препарат tislelizumab
  Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 3 cycles.
• Препарат tislelizumab
  Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 5 cycles.
• Препарат Gemcitabine + cisplatin (GP)
  neoadjuvent gemcitabine (1000 mg/m2 d1, d8) and cisplatin (80 mg/m2 d1) every 3 weeks for 3 cycles
• Препарат Cisplatin (100mg/m2)
  Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
• Лучевая терапия intensity-modulated radiotherapy
  Defnitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.

Первичные конечные точки

• Failure-free survival (FFS) [Срок оценки: 3 years]

Вторичные конечные точки (6)

• Overall survival (OS) [Срок оценки: 3 years]
• Distant metastasis-free survival (DMFS) [Срок оценки: 3 years]
• Locoregional recurrence-free survival (LRRFS) [Срок оценки: 3 years]
• Adverse events (AEs) [Срок оценки: within 5 years]
• Quality of life (QoL) [Срок оценки: week 0, 9, 16, 28, 40 and 1 year, 2 years, 3 years, 4 years, and 5 years after randomization]
• cost-effectiveness analysis [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Age ≥18 and ≤65 years
• Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria.
• Eastern Cooperative Oncology Group performance score of 0-1.
• Tumor staged as T4N1 and T1-4N2-3 disease (AJCC 9th edition).
• Adequate marrow function:

white blood cell count > 4 × 10⁹/L hemoglobin >90g/L and platelet count >100×10⁹/L

• Adequate hepatic and renal function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN), Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN, Alkaline phosphatase ≤ 2.5 ×ULN, clearance rate ≥ 60 ml/min 7. Other laboratory and clinical criteria Normal: thyroid function, serum amylase and lipase, pituitary hormone levels, inflammatory markers, cardiac enzyme tests and electrocardiogram (ECG); For patients aged >50 years with a history of smoking, normal pulmonary function test (PFT) results are required; For patients with abnormal ECG findings or a prior history of cardiovascular disease (not meeting any exclusion criteria listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits.

8\. Patients must be informed of the investigational nature of this study and give written informed consent, and be willing and able to comply with the study schedule, including follow-up visits, treatment procedures, laboratory testing, and other protocol-related requirements.

9\. Women of childbearing potential (WOCBP) must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug.

Критерии исключения

• Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA >1×10 copies/mL, positive for anti-hepatitis C virus (HCV) antibody, positive for anti-hepatitis C virus (HCV) antibody
• Positive for anti-HIV antibody or diagnosed with acquired immunodeficiency syndrome (AIDS).
• Active pulmonary tuberculosis: Patients with a history of active tuberculosis within the past year should be excluded regardless of treatment status. Patients with a history of active pulmonary tuberculosis more than one year prior should also be excluded, unless they received con dirmed and regular anti-tuberculosis treatment.
• Active, known, or suspected autoimmune diseases, including but not limited to uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, systemic lupus erythematosus, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators. Type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are allowed.
• History of interstitial lung disease or pneumonia requiring oral or intravenous corticosteroids within the past year; use of vancomycin within the past month.
• Ongoing chronic systemic corticosteroid therapy (equivalent to or greater than prednisone >10mg per day) or any other immunosuppressive therapy. Patients received inhale or topical corticosteroid are allowed.
• Uncontrolled cardiac conditions, such as: Heart failure with New York Heart Association (NYHA) classi dication ≥ Class II; or Unstable angina; or History of myocardial infarction within the past year; or Supraventricular or ventricular arrhythmias requiring treatment or intervention
• Pregnant or breastfeeding women (pregnancy testing should be considered for women of childbearing potential with active sexual life)
• History or presence of other malignancies, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
• Known hypersensitivity to macromolecule protein products.
• Active infections requiring systemic treatment within 1 week prior to enrollment.
• Administration of live vaccines within 30 days prior to the first dose of tile.
• History of organ transplantation or hematopoietic stem cell transplantation.
• Any other condition assessed by the investigator as potentially compromising patient safety or compliance, such as severe illnesses requiring urgent treatment (including psychiatric disorders), significantly abnormal laboratory values, or other psychological, familial, or social risk factors.
• Patients who have previously received immune checkpoint (CTLA-4, PD-1, PD-L1, etc.) inhibitor therapy.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07373990 · 2025-FXY-462-FLK

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗