Maintenance Immunotherapy With Deferred Salvage Radiotherapy in Patients With an Objective Response to Chemoimmunotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma: A Multicenter Phase 2 Single-Arm Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 62
- 试验地点
- 4
- 主要终点
- Overall survival
研究概览
简要总结
Re-irradiation is the most common clinical treatment for recurrent nasopharyngeal carcinoma; however, it is associated with severe complications which seriously affect patients' quality of life.
Exploring deferred salvage radiotherapy until nasopharyngeal or cervical progression after PD 1 plus GP chemotherapy and immunotherapy maintenance is of great significance for improving the long-term survival and quality of life of patients with unresectable locally recurrent NPC.
Thus, the investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial to evaluate the efficacy and safety of maintenance Immunotherapy with deferred salvage radiotherapy with an objective response to chemoimmunotherapy in patients with unresectable locally recurrent NPC .
详细描述
Re-irradiation is the most common clinical treatment for recurrent nasopharyngeal carcinoma; however, it is associated with severe complications (such as radiation-induced nasopharyngeal necrosis, radiation encephalopathy, trismus, profound hearing loss, and cervical muscle stiffness), which seriously affect patients' quality of life.
The addition of immunotherapy plays an important role in disease control for recurrent or metastatic NPC (RM-NPC) and PD-1 antibody plus gemcitabine-cisplatin (GP) chemotherapy has become the current standard of care for the first-line treatment of RM-NPC. Exploring deferred salvage radiotherapy until nasopharyngeal and/or cervical progression after PD 1 plus GP chemotherapy and immunotherapy maintenance is of great significance for improving the long-term survival and quality of life of patients with unresectable locally recurrent NPC.
Thus, the investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial to evaluate the efficacy and safety of of maintenance Immunotherapy with deferred salvage radiotherapy with an objective response to chemoimmunotherapy in patients with unresectable locally recurrent NPC .
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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.
- •primary tumour recurrent T classificationT2-T4, regional lymph nodes recurrent N classificationN0-N2, no distant metastasis (recurrent M0); overall recurrent stage II-III according to the American Joint Committee on Cancer Union for International Cancer Control 9th edition stage-classification system.
- •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 ≥ 50 mL/min Liver Function：Total bilirubin ≤ 1.5 × ULN，AST and ALT ≤ 2.5 × ULN.
- •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
- •known pre-existing radiation-induced complications, including soft tissue necrosis, brain injury, neck fibrosis, or other radiation-induced complications of grade 3 or above
- •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 more than 1000 copies/mL or 200 IU/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
干预措施: PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy (Drug)
结局指标
主要结局
Overall survival
时间窗: 3 years
the time from the date of maintenance treatment initiation to the date of death due to any cause.
次要结局
- Incidence of toxicity(3 years)
- Quality of life (QoL)(3 years)
- Progression free-survival(3 years)
- Locoregional progression-free survival(3 years)
- Distant progression-free survival(3 years)
- Incidence of acute and late toxicity(3 years)
研究者
Hai-Qiang Mai,MD,PhD
Principal Investigator
Sun Yat-sen University