Short-course Tislelizumab Combined With Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled, Multicenter, Phase 3 Non-inferiority Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 418
- 主要终点
- Failure-free survival (FFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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
- •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
排除标准
- •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.
- •Exclusion Criteria:
- •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.
研究组 & 干预措施
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
干预措施: tislelizumab (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
干预措施: Gemcitabine + cisplatin (GP) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
干预措施: Cisplatin (100mg/m2) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
干预措施: intensity-modulated radiotherapy (Radiation)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
干预措施: tislelizumab (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
干预措施: Gemcitabine + cisplatin (GP) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
干预措施: Cisplatin (100mg/m2) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
干预措施: intensity-modulated radiotherapy (Radiation)
结局指标
主要结局
Failure-free survival (FFS)
时间窗: 3 years
From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.
次要结局
- Overall survival (OS)(3 years)
- Distant metastasis-free survival (DMFS)(3 years)
- Locoregional recurrence-free survival (LRRFS)(3 years)
- Adverse events (AEs)(within 5 years)
- Quality of life (QoL)(week 0, 9, 16, 28, 40 and 1 year, 2 years, 3 years, 4 years, and 5 years after randomization)
- cost-effectiveness analysis(3 years)
研究者
Jun Ma, MD
Professor
Sun Yat-sen University