Real-World RAIRI-Guided Risk Stratification for Adjuvant Therapy Benefit After Chemoradiotherapy in NPC

NCT07618078 | Recruiting DMC FDA Drug

• 1 other identifier: 26/007-5732
• Study Type: observational
• Target: 900
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, multicenter, real-world observational study aims to evaluate whether a response-adapted individualized risk index, the RAIRI model, can identify patients with non-metastatic nasopharyngeal carcinoma who may or may not benefit from adjuvant therapy after standard chemoradiotherapy. Patients will receive standard treatment according to routine clinical practice. After completion of chemoradiotherapy and assessment at approximately 1 month after radiotherapy, longitudinal multimodal response data, including plasma cfEBV DNA dynamics and MRI-based tumor response, will be incorporated into the RAIRI model to estimate the predicted 5-year progression-free survival. Patients will be stratified into a RAIRI low-risk group, defined as predicted 5-year PFS ≥85%, and a RAIRI high-risk group, defined as predicted 5-year PFS \<85%. Within each RAIRI risk stratum, outcomes will be compared between patients who receive adjuvant systemic therapy, mainly PD-1 inhibitor-based adjuvant immunotherapy, and those who undergo routine surveillance without adjuvant systemic therapy. The primary endpoint is 3-year failure-free survival. Secondary endpoints include overall survival, locoregional relapse-free survival, distant metastasis-free survival, complete response rate after chemoradiotherapy, distribution of RAIRI risk groups, adverse events, late toxicities, and longitudinal health-related quality of life.

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

RAIRI; EBV-DNA; Adjuvant Therapy; Risk Stratification; response-adapted

Outcome Measures

Primary Outcomes (1)

• 3-year Failure-Free Survival (FFS)

  FFS is defined as the time from enrollment to locoregional recurrence, distant metastasis, or death from any cause.

  Up to 3 years

Secondary Outcomes (6)

• 3-year Overall Survival (OS)

  Up to 3 years

• 3-year Locoregional Relapse-Free Survival (LRRFS)

  Up to 3 years

• 3-year Distant Metastasis-Free Survival (DMFS)

  Up to 3 years

• Complete Response (CR) Rate after Chemoradiotherapy

  1 month after the completion of radiotherapy

• Incidence of Acute and Late Toxicities and Adverse Events

  From the start of treatment up to 3 years

Study Arms (2)

Routine Surveillance Group

Patients who do not receive adjuvant systemic therapy after completion of standard chemoradiotherapy and enter routine post-treatment surveillance according to standard clinical practice. Treatment decisions are made by treating physicians and patients, not assigned by the study protocol.

Adjuvant Therapy Group

Patients who receive adjuvant systemic therapy after completion of standard chemoradiotherapy in routine clinical practice, mainly PD-1 inhibitor-based adjuvant immunotherapy. The specific agent, dose, duration, treatment interruption, and discontinuation are determined by treating physicians and prospectively recorded.

Drug: PD-1 inhibitor; Drug: Capecitabine

Interventions

PD-1 inhibitor DRUG

Administered intravenously every 3 weeks for up to 12 cycles as adjuvant therapy.

Adjuvant Therapy Group

Capecitabine DRUG

Metronomic capecitabine administered orally at a dose of 650 mg/m2 twice daily for one year as adjuvant therapy.

Adjuvant Therapy Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 to 75 years with histologically or cytologically confirmed EBER-positive, non-keratinizing, non-metastatic nasopharyngeal carcinoma who are scheduled to receive standard chemoradiotherapy with or without induction therapy in routine clinical practice. Eligible patients must have pretreatment contrast-enhanced MRI of the nasopharynx and neck, pretreatment quantitative plasma cfEBV DNA measurement, ECOG performance status of 0-1, adequate baseline organ function, and reliable follow-up conditions. After completion of chemoradiotherapy, patients may either receive adjuvant systemic therapy, mainly PD-1 inhibitor-based immunotherapy, or undergo routine surveillance according to treating physician judgment and patient preference.

You may qualify if:

• Age 18 to 75 years, male or female.
• Histologically or cytologically confirmed EBER-positive non-keratinizing nasopharyngeal carcinoma, including differentiated or undifferentiated subtype.
• Non-metastatic nasopharyngeal carcinoma confirmed by multimodal staging, corresponding to stage I-III according to the AJCC 9th edition staging system, or stage I-IVA according to the AJCC 8th edition staging system.
• Eastern Cooperative Oncology Group performance status of 0-1.
• Availability of complete pretreatment high-quality contrast-enhanced MRI of the nasopharynx and neck, including functional MRI sequences such as diffusion-weighted imaging, and at least one measurable tumor lesion according to RECIST version 1.1.
• Availability of pretreatment quantitative plasma cfEBV DNA measurement.
• Adequate baseline laboratory function, defined as hemoglobin \>120 g/L, white blood cell count ≥4 × 10\^9/L, platelet count ≥100 ×10\^9/L, and liver and renal function parameters, including ALT, AST, total bilirubin, and serum creatinine, within 1.25 times the upper limit of normal; no severe clinically significant hearing impairment.
• Ability to fully understand the nature and follow-up procedures of this observational study, and voluntary provision of written informed consent by the patient or the patient's legally authorized representative.
• Agreement to allow the research team to use the patient's clinical data, routine diagnostic imaging data, and residual biospecimens, such as peripheral blood samples and pathological slides, for scientific research analyses.
• Adequate major organ function, except for local compression or functional impairment directly attributable to nasopharyngeal carcinoma.
• Good expected compliance with follow-up and reliable communication conditions, allowing completion of long-term survival follow-up.

You may not qualify if:

• Absence of pretreatment plasma cfEBV DNA measurement, or missing key baseline clinical variables required for RAIRI model calculation, such as age, AJCC stage, lactate dehydrogenase level, or central liquefactive necrosis status.
• Presence of distant metastatic disease, M1.
• History of previous or concurrent malignancy, except for non-melanoma skin cancer or cervical carcinoma in situ that has been successfully treated and has remained disease-free for more than 5 years.
• Pregnant or breastfeeding women, or participants of reproductive potential who are unwilling to use effective contraception during the study observation period.
• Current participation in another interventional clinical trial involving an investigational drug or medical device.
• Severe or uncontrolled comorbidities, including myocardial infarction within the past 6 months, severe unstable arrhythmia, severe cerebrovascular accident, active gastrointestinal ulcer, uncontrolled psychiatric illness, uncontrolled diabetes mellitus, active autoimmune disease, long-term systemic immunosuppressive therapy, active severe infection requiring systemic anti-infective treatment, known history of human immunodeficiency virus infection, hepatitis B surface antigen positivity with HBV DNA \>1 × 10³ copies/mL or \>200 IU/mL, or hepatitis C virus antibody positivity with abnormal viral load.
• Any personal, social, geographic, or psychiatric condition that, in the investigator's judgment, would make it impossible for the participant to complete regular follow-up visits and assessments.

Sponsors & Collaborators

• Xiangya Hospital of Central South University: collaborator
• Peking University Cancer Hospital & Institute: collaborator
• Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center: collaborator
• Fujian Cancer Hospital: collaborator
• Hunan Cancer Hospital: collaborator
• Cancer Hospital of Guizhou Province: collaborator
• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead
• Xijing Hospital: collaborator
• Sun Yat-Sen University Cancer Center: collaborator

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Clinically collected peripheral blood samples and residual diagnostic pathological specimens may be retained for exploratory biomarker analyses related to treatment response and prognosis.

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Immune Checkpoint Inhibitors; Capecitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Junlin Yi

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yang Liu

CONTACT

+86 18801342502; 530669421@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Radiation Oncology

Study Record Dates

• First Submitted: May 25, 2026
• First Posted: June 1, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available beginning 6 months following article publication.
• Access Criteria: Data will be shared with researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose. Proposals should be directed to the corresponding author's email.

Locations

CN (1)