An Open-Label, Randomized Controlled Phase II Clinical Trial of PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Selective Re-irradiation for Locally Advanced Recurrent Nasopharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
This phase II randomized trial evaluates PD-1 inhibitor plus chemotherapy followed by immediate versus selective re-irradiation in locally advanced recurrent nasopharyngeal carcinoma. The study aims to determine whether sequential radiotherapy provides additional survival benefit beyond systemic immunochemotherapy.
详细描述
Nasopharyngeal carcinoma (NPC) is prevalent in Southern China, and 10~15% of patients experience local recurrence, which presents significant treatment challenges. PD-1 inhibitor plus gemcitabine-cisplatin (GP) has become the standard first-line therapy for recurrent/metastatic NPC. However, the survival benefit of adding sequential re-irradiation after GP + PD-1 in locally advanced recurrent nasopharyngeal carcinoma remains uncertain.This phase II randomized trial aims to compare immediate versus selective re-irradiation following PD-1 inhibitor plus GP in locally advanced recurrent NPC, to determine whether sequential re-irradiation provides additional survival benefit without excessive 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.
- •Local recurrence (with or without regional recurrence) more than one year after radical treatment and unsuitable for surgery.
- •Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO type II or III).
- •Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.
- •ECOG performance status 0-
- •Expected survival ≥ 3 months.
- •No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent nasopharyngeal carcinoma
- •No contraindications to immunotherapy, chemotherapy, or re-irradiation.
- •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
- •Presence of grade 3 or higher late radiation toxicity (excluding skin, subcutaneous tissue, and mucosa) at the time of recurrence
- •Prior anti-tumor therapy for recurrent nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy.
- •Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors.
- •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
Selective re-irradiation group
PD-1 inhibitor maintenance + Selective re-irradiation:
PD-1 inhibitor maintenance therapy:Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1; if progression occurs in the nasopharynx or neck, re-irradiation will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.
干预措施: Selective re-irradiation (Radiation)
Immediate re-irradiation group
Immediate re-irradiation + PD-1 inhibitor Maintenance:
Re-irradiation will be administered Immediately. PD-1 inhibitor maintenance therapy: Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.
干预措施: Immediate re-irradiation (Radiation)
结局指标
主要结局
Overall survival
时间窗: 3 year
the time from the date of randomization to the date of death due to any cause.
次要结局
- Progression free-survival(3 year)
- Progression free-survival 2(3 year)
- Distant progression-free survival(3 year)
- Locoregional progression-free survival(3 year)
- Incidence of Acute and Late Toxicity(3 year)
- Quality of life (QoL)(3 year)
研究者
Hai-Qiang Mai,MD,PhD
Principal Investigator
Sun Yat-sen University