RAIRI-Guided Adjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma

NCT07590024 | Recruiting Phase 3 DMC

• 1 other identifier: 25/259-0259
• Study Type: interventional
• Target: 651
• Locations: 1 country
• Sites: 1

Brief Summary

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:

1. 1.Standard Treatment Group: All patients will receive standard adjuvant therapy (either a PD-1 inhibitor or capecitabine) after completing their initial chemoradiotherapy.
2. 2.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.

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 3-year Failure-Free Survival (FFS)

  FFS is defined as the time from randomization 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 radiotherap

• Incidence of Acute and Late Toxicities and Adverse Events

  From the start of treatment up to 3 years

Study Arms (2)

Standard Treatment Arm

ACTIVE COMPARATOR

Patients in this arm will receive standard concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC). Following CCRT, all patients will receive standard adjuvant therapy, consisting of either a PD-1 inhibitor (administered intravenously every 3 weeks for up to 12 cycles) or metronomic capecitabine (650mg/m2 orally twice daily for one year), based on the investigator's discretion.

Drug: PD-1 inhibitor; Drug: Capecitabine

Experimental Arm: RAIRI-Guided

EXPERIMENTAL

Patients will receive standard CCRT with or without IC. After radiotherapy, patients are stratified using the Response-Adapted Individualized Risk Index (RAIRI) model. Patients identified as RAIRI Low-Risk (predicted 5-year PFS ≥ 85%) will be exempted from adjuvant therapy and undergo regular observation. Patients identified as RAIRI High-Risk (predicted 5-year PFS \< 85%) will receive adjuvant therapy (PD-1 inhibitor or capecitabine).

Drug: PD-1 inhibitor; Drug: Capecitabine

Interventions

PD-1 inhibitor DRUG

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

Experimental Arm: RAIRI-Guided; Standard Treatment Arm

Capecitabine DRUG

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

Experimental Arm: RAIRI-Guided; Standard Treatment Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

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, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yang Liu, MD

CONTACT

+86 18801342502; 530669421@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: May 15, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 20, 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)