Induction Chemotherapy Combined With Serplulimab Induction/Maintenance Therapy and Omission of Concurrent Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma (UNION-NPC-001): A Multicenter, Open-Label, Randomized, Controlled, Phase III, Non-Inferiority Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 710
- 试验地点
- 2
- 主要终点
- Incidence of Hearing Loss (any grade)
研究概览
简要总结
This phase III trial aims to evaluate the efficacy and safety of induction chemotherapy combined with serplulimab (induction/maintenance therapy) with omission of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).
详细描述
This multicenter phase III trial enrolls high-risk locally advanced nasopharyngeal carcinoma patients (AJCC 9th edition, Stage T1-3N2 [II] or T1-4N3/T4N1-2 [III]) who achieves ≥50% tumor regression (RECIST v1.1) and undetectable plasma EBV DNA after three cycles of GP induction chemotherapy (gemcitabine + cisplatin) combined with serplulimab. Eligible patients will be randomized to either:
Experimental arm: Radiotherapy alone followed by serplulimab maintenance, or Control arm: Cisplatin-based concurrent chemoradiotherapy (CCRT) followed by serplulimab maintenance.
Primary study endpoint
-
event-free survival (EFS) ② overall survival (OS) ③ Incidence of Hearing Loss (any grade) Secondary study endpoints
-
3-year distant metastasis-free survival (DMFS)
-
3-year locoregional recurrence-free survival (LRFS)
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 at diagnosis: 18-65 years;
- •Pathologically confirmed treatment-naïve nasopharyngeal carcinoma of "non-keratinizing type (WHO classification)";
- •Locoregionally advanced nasopharyngeal carcinoma staged per the 9th edition of the American Joint Committee on Cancer (AJCC) staging system: Stage II (T1-3N2), Stage III(T1-4N3 or T4N1-2);
- •ECOG performance status: 0-1;
- •Post-induction therapy requirements:
- •Radiological assessment showing ≥50% tumor regression (RECIST 1.1) Undetectable plasma EBV DNA levels;
- •Adequate bone marrow function:
- •White blood cell count >4×10⁹/L Hemoglobin >90 g/L Platelet count >100×10⁹/L;
- •Normal hepatic/renal function:
- •Total bilirubin ≤1.5×upper limit of normal (ULN) AST/ALT ≤2.5×ULN Alkaline phosphatase ≤2.5×ULN Creatinine clearance ≥60 mL/min;
- •Normal results for:
- •Thyroid function tests Amylase and lipase Pituitary function Inflammatory/infection markers Cardiac enzymes Electrocardiogram
- •Additional requirements:
- •Pulmonary function tests for smokers >50 years Cardiac ultrasound + myocardial function tests for patients with ECG abnormalities or cardiovascular history (unless meeting exclusion criterion (8));
- •Signed informed consent with willingness/compliance to follow study schedules for treatment, follow-up, and laboratory tests;
- •For women of childbearing potential: Agreement to use reliable contraception (e.g., condoms, prescribed oral contraceptives) from screening until 1 year post-treatment.
排除标准
- •Hepatitis B Virus (HBV) Infection:
- •HBsAg-positive with HBV DNA >1×10³ copies/mL (patients with controlled viremia [<1×10³ copies/mL] after antiviral therapy are eligible).
- •Hepatitis C Virus (HCV) Infection: Anti-HCV antibody-positive.
- •HIV/AIDS: Anti-HIV antibody-positive or diagnosed with acquired immunodeficiency syndrome (AIDS).
- •Active Tuberculosis (TB): History of active TB within the past year (regardless of treatment status). Exception: Patients with adequately treated past TB (confirmed by standard anti-TB therapy) may be enrolled if >1 year since completion of treatment.
- •Active Autoimmune Diseases:Known or suspected autoimmune disorders (e.g., uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism, or asthma requiring bronchodilators).
- •Exceptions:
- •Type 1 diabetes mellitus Hypothyroidism managed with hormone replacement Skin conditions not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia).
- •Interstitial Lung Disease (ILD):
- •History of ILD or pneumonitis requiring oral/IV steroids within the past year.
- •Immunosuppressive Therapy:
- •Chronic systemic corticosteroids (≥10 mg prednisone equivalent/day) or other immunosuppressants within 4 weeks prior to enrollment. Inhaled/topical steroids are permitted.
- •Uncontrolled Cardiac Disease: Heart failure (NYHA class ≥2), Unstable angina, Myocardial infarction within the past year, Clinically significant arrhythmias requiring treatment.
- •Pregnancy/Lactation: Pregnant or breastfeeding women (urine/blood pregnancy test required for women of childbearing potential).
- •Concurrent Malignancies:
- •History of other malignancies except:
- •Adequately treated non-melanoma skin cancer, Carcinoma in situ of the cervix, Papillary thyroid carcinoma.
- •Hypersensitivity: Known allergy to any component of the study drugs or excipients.
- •Active Infections:
- •Systemic infections requiring treatment within 1 week prior to enrollment.
- •Live Vaccines:
- •Administration of live vaccines within 30 days before the first immunotherapy dose.
- •Organ Transplantation: History of allogeneic organ transplantation.
- •Other High-Risk Conditions:
- •Any condition that may compromise patient safety or compliance per investigator assessment (e.g., severe psychiatric disorders, life-threatening comorbidities, or social/familial risk factors).
研究组 & 干预措施
Control arm
Cisplatin-based concurrent chemoradiotherapy (CCRT)
干预措施: Cisplatin (Drug)
Experimental arm
Radiotherapy
干预措施: Serplulimab (Drug)
Control arm
Cisplatin-based concurrent chemoradiotherapy (CCRT)
干预措施: Serplulimab (Drug)
Control arm
Cisplatin-based concurrent chemoradiotherapy (CCRT)
干预措施: Radiotherapy (Radiation)
Experimental arm
Radiotherapy
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Incidence of Hearing Loss (any grade)
时间窗: 3 years after radiotherapy
Proportion of participants experiencing any grade of hearing loss, assessed by pure-tone audiometry, auditory brainstem response, and acoustic immittance.
Event-free survival (EFS)
时间窗: 3-year
EFS is defined as the time from the date of randomization to the first occurrence of disease recurrence (locoregional or distant) or death from any cause, whichever comes first.
Overall survival (OS)
时间窗: 5-year
OS is defined as the time from the date of randomization until death from any cause.
Incidence rate of all-grade vomiting
时间窗: Through study completion, an average of 1 year
Incidence rate of all-grade vomiting during treatment assessed by clinicians according to the Common Terminology Criteria for Adverse Events 5.0.
次要结局
- Distant metastasis-free survival (DMFS)(3-year)
- Locoregional recurrence-free survival (LRFS)(3-year)
- Health-Related Quality of Life assessed by EORTC QLQ-C30(From baseline (at informed consent) up to 60 months after radiotherapy completion.)
- Head and Neck Cancer-Specific Symptoms assessed by EORTC QLQ-H&N35(From baseline (informed consent) until 60 months after radiotherapy completion.)
- Incidence rate of patient-reported adverse events (AEs)(3-year)
- Incidence rate of investigator-reported adverse events (AEs)(3-year)