A Multicenter, Open-Label, Randomized Phase III Non-Inferiority Trial of PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Salvage Locoregional Radiotherapy in De Novo Metastatic Nasopharyngeal Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 260
- 试验地点
- 7
- 主要终点
- Overall survival
研究概览
简要总结
This phase III randomized trial evaluates PD-1 inhibitor plus chemotherapy followed by immediate versus salvage locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma. The study aims to evaluate whether salvage locoregional radiotherapy is non-inferior to immediate radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with potential for reduced toxicity.
详细描述
Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China, with approximately 15% of patients presenting with distant metastases at diagnosis. A PD-1 inhibitor combined with gemcitabine and cisplatin (GP) has become the standard first-line therapy for metastatic NPC. However, the survival benefit of adding immediate locoregional radiotherapy to PD-1 inhibitor plus GP in de novo metastatic NPC remains uncertain. This phase III randomized trial is designed to compare immediate versus salvage locoregional radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with the objective of determining whether salvage radiotherapy is non-inferior to immediate radiotherapy while offering reduced toxicity.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-70 years, any gender.
- •Histologically confirmed differentiated non-keratinizing carcinoma or undifferentiated non-keratinizing carcinoma by tissue biopsy, with radiologically detectable metastatic lesions. Pathological confirmation of metastatic lesions is recommended but not mandatory.
- •ECOG performance status 0-
- •Stage IV NPC according to the 9th edition of the UICC/AJCC staging system.
- •No prior anti-tumor treatment for NPC (radiotherapy, chemotherapy, surgery, etc.).
- •Expected survival ≥ 3 months.
- •At least one measurable lesion per RECIST v1.
- •Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.
- •Adequate organ function within 14 days before first dose, defined as:
- •Hematology：Hemoglobin ≥ 90 g/L，ANC ≥ 1.5 × 10⁹/L，Platelet count ≥ 100 × 10⁹/L Renal Function：Creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) / eGFR ≥ 60 mL/min Liver Function：Total bilirubin ≤ 1.5 × ULN，AST and ALT ≤ 2.5 × ULN, or ≤ 5 × ULN in the presence of liver metastases
- •INR or PT ≤ 1.5 × ULN, unless on therapeutic anticoagulation and values within therapeutic range，aPTT ≤ 1.5 × ULN, unless on therapeutic anticoagulation and values within therapeutic range
排除标准
- •Prior anti-tumor therapy for nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy.
- •Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors.
- •Presence of uncontrolled or symptomatic central nervous system (CNS) metastases.
- •History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell skin cancer, or in-situ cervical cancer.
- •Active autoimmune disease or history of autoimmune disease requiring systemic treatment (e.g., corticosteroids, immunosuppressants) within the past 2 years, except for stable hypothyroidism, type 1 diabetes mellitus, or resolved childhood asthma/atopy.
- •Known history of active pulmonary tuberculosis (TB). Suspected active TB must be excluded by chest X-ray, sputum examination, and assessment of clinical signs and symptoms.
- •Hepatitis B: HBsAg positive with peripheral blood HBV DNA ≥ 1000 copies/mL
- •Hepatitis C: HCV antibody positive, eligible only if HCV RNA is negative
- •HIV infection
- •Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within 6 months, congestive heart failure ≥ NYHA class II, or serious arrhythmia).
- •Interstitial lung disease, non-infectious pneumonitis, or history of ≥ grade 2 pneumonitis.
- •Major surgery within 4 weeks before enrollment, or unhealed surgical wound.
- •Pregnant or breastfeeding women, or those planning pregnancy during the study period.
- •Known allergy or hypersensitivity to study drugs or their excipients.
- •Any condition that, in the investigator's judgment, would interfere with trial participation or interpretation of results.
研究组 & 干预措施
Immediate locoregional radiotherapy group
Immediate locoregional radiotherapy
干预措施: Immediate locoregional radiotherapy (Radiation)
Salvage locoregional radiotherapy group
Salvage locoregional radiotherapy
干预措施: Salvage locoregional radiotherapy (Radiation)
结局指标
主要结局
Overall survival
时间窗: 2 year
Defined as the time from random assignment to death from any cause.
次要结局
- Locoregional progression-free survival(2 year)
- Distant progression-free survival(2 year)
- Progression free-survival(2 year)
- Incidence of Acute and Late Toxicity(2 year)
- Quality of life (QoL)(1 year)
研究者
Hai-Qiang Mai,MD,PhD
Principal Investigator
Sun Yat-sen University