Individualized Adjuvant Therapy Decision-Making for Locoregionally Advanced Nasopharyngeal Carcinoma Guided by Response-Adapted Individualized Risk Index (RAIRI): A Multicenter, Randomized, Controlled Phase III Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 651
- 试验地点
- 1
研究概览
简要总结
This study aims to evaluate a personalized approach for treating patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Currently, many high-risk patients receive additional treatment (adjuvant therapy) after standard chemoradiotherapy to prevent the cancer from returning. However, some patients may not actually need this extra treatment and could safely avoid its side effects.
This trial uses a novel risk prediction model called the Response-Adapted Individualized Risk Index (RAIRI). The RAIRI model evaluates how a patient's tumor and blood markers (such as Epstein-Barr Virus DNA) respond during and immediately after their initial chemoradiotherapy.
In this study, patients will be randomly assigned to one of two groups:
- Standard Treatment Group: All patients will receive standard adjuvant therapy (either a PD-1 inhibitor or capecitabine) after completing their initial chemoradiotherapy.
- RAIRI-Guided Group (Experimental): Patients will be evaluated using the RAIRI model after initial chemoradiotherapy. Only those identified as "high-risk" by the model will receive adjuvant therapy. Those identified as "low-risk" will be exempted from adjuvant therapy and will undergo regular observation.
The main goal of this study is to determine if using the RAIRI model to exempt low-risk patients from adjuvant therapy is as safe and effective as giving adjuvant therapy to everyone, measured by how long patients live without the disease returning or progressing.
详细描述
Background and Rationale Locoregionally advanced nasopharyngeal carcinoma is commonly treated with definitive intensity-modulated radiotherapy combined with platinum-based chemotherapy, with or without induction therapy. Although modern radiotherapy and systemic treatment have substantially improved disease control, a considerable proportion of patients remain at risk of locoregional recurrence, distant metastasis, or death after standard treatment.
Adjuvant therapy, including metronomic capecitabine or PD-1 inhibitor monotherapy, has been shown to improve failure-free or event-free survival in selected high-risk patients. However, the absolute survival benefit is modest, and many patients may receive unnecessary adjuvant treatment, resulting in additional toxicity, prolonged treatment duration, increased financial burden, and impaired quality of life.
Current adjuvant treatment decisions are mainly based on pretreatment clinical risk factors, such as tumor stage, nodal stage, and baseline plasma Epstein-Barr virus DNA level. These static baseline factors do not fully capture interpatient heterogeneity in treatment response. Increasing evidence suggests that dynamic treatment-response markers, including longitudinal changes in plasma cell-free Epstein-Barr virus DNA and radiographic tumor regression during or after treatment, provide important prognostic information. A response-adapted strategy may therefore allow more precise identification of patients who can safely omit adjuvant treatment and those who may still require additional therapy.
RAIRI Model The response-adapted individualized risk index, or RAIRI, was developed to provide individualized dynamic risk prediction for patients with non-metastatic nasopharyngeal carcinoma. The model incorporates baseline clinical factors, longitudinal plasma cell-free Epstein-Barr virus DNA changes, and imaging-based tumor response assessments collected during treatment.
In prior validation cohorts, RAIRI showed favorable calibration and discrimination for predicting progression-free survival and overall survival. The model also demonstrated potential value for predicting the benefit of adjuvant chemotherapy. Patients categorized as RAIRI low-risk had favorable long-term outcomes and appeared to derive limited benefit from adjuvant capecitabine, whereas RAIRI high-risk patients were more likely to benefit from intensified adjuvant treatment.
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 18-65 years, regardless of sex.
- •Histologically confirmed EBER-positive, non-metastatic, non-keratinizing nasopharyngeal carcinoma.
- •AJCC 9th edition stage II-III disease / AJCC 8th edition stage III-IVA disease, excluding T3-T4N0 and T3N1 disease; or baseline EBV DNA >4,000 copies/mL.
- •Eastern Cooperative Oncology Group performance status score of 0-
- •Availability of complete baseline pretreatment imaging data, including nasopharyngeal and neck MRI with functional MRI sequences, and at least one measurable tumor lesion.
- •Availability of pretreatment baseline plasma cfEBV-DNA measurement.
- •Patients must meet the following laboratory criteria: hemoglobin >120 g/L and white blood cell count ≥4 × 10⁹/L.
- •Platelet count ≥100 × 10⁹/L; liver and renal function parameters within 1.25 times the upper limit of normal; and no hearing impairment.
- •Ability to understand the study and provision of written informed consent.
- •Agreement to allow the use of personal data and biological samples, including blood and tissue samples, for research purposes.
- •Adequate function of major organs, except for abnormalities related to nasopharyngeal carcinoma.
- •Ability and willingness to comply with scheduled follow-up.
排除标准
- •Absence of pretreatment cfEBV-DNA data or other essential baseline characteristic data.
- •AJCC 8th edition stage I-II or IVB disease / AJCC 9th edition stage I or IV disease, or T3-4N0 or T3N1 disease.
- •History of other malignancies, except stage I non-melanoma skin cancer or carcinoma in situ of the cervix.
- •Pregnant or lactating women, or women of childbearing potential who are not using contraception.
- •Current participation in another investigational drug trial.
- •Severe comorbidities, including myocardial infarction, severe arrhythmia, severe cerebrovascular disease, active ulcer disease, psychiatric illness, uncontrolled diabetes mellitus, active autoimmune disease, ongoing systemic immunosuppressive therapy, active infection requiring systemic treatment, history of human immunodeficiency virus infection, positive hepatitis B surface antigen, hepatitis B virus DNA >1 × 10³ copies/mL or >200 IU/mL, or positive hepatitis C virus antibody.
- •Inability to comply with regular follow-up.
研究者
Yi Junlin
Professor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences