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

June 1, 2026 updated by: Yi Junlin, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

A Prospective, Multicenter, Real-World Observational Study to Evaluate RAIRI-Guided Risk Stratification for Identifying Adjuvant Therapy Benefit After Standard Chemoradiotherapy in Nasopharyngeal Carcinoma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Nasopharyngeal carcinoma is commonly treated with intensity-modulated radiotherapy combined with platinum-based chemotherapy, with or without induction therapy. However, the optimal selection of patients for adjuvant systemic therapy after definitive chemoradiotherapy remains uncertain in routine clinical practice. Some patients may have a sufficiently favorable prognosis after chemoradiotherapy and may be safely observed, whereas others may remain at high risk of recurrence or metastasis and may benefit from treatment intensification.

This study will prospectively collect real-world clinical, imaging, laboratory, treatment exposure, toxicity, and survival data from patients with non-metastatic nasopharyngeal carcinoma treated at multiple tertiary cancer centers. The RAIRI dynamic prognostic model will be applied after completion of standard chemoradiotherapy, using baseline clinical variables and longitudinal response indicators including cfEBV DNA kinetics and MRI-based tumor regression. The model will generate an individualized predicted 5-year PFS probability. Patients with predicted 5-year PFS ≥85% will be classified as RAIRI low-risk, whereas those with predicted 5-year PFS <85% will be classified as RAIRI high-risk.

Because this is an observational study, adjuvant treatment will not be assigned by the study protocol. After chemoradiotherapy, patients may either receive adjuvant systemic therapy, mainly PD-1 monoclonal antibody therapy, or undergo routine surveillance, according to treating physician judgment and patient preference. The main analysis will compare 3-year failure-free survival between adjuvant therapy and routine surveillance within each RAIRI risk group. Propensity score matching, multivariable Cox proportional hazards models, and sensitivity analyses will be used to adjust for baseline and treatment-related confounders.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
900

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100021
        • Recruiting
        • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Description

Inclusion Criteria

  1. Age 18 to 75 years, male or female.
  2. Histologically or cytologically confirmed EBER-positive non-keratinizing nasopharyngeal carcinoma, including differentiated or undifferentiated subtype.
  3. 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.
  4. Eastern Cooperative Oncology Group performance status of 0-1.
  5. 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.
  6. Availability of pretreatment quantitative plasma cfEBV DNA measurement.
  7. 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.
  8. 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.
  9. 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.
  10. Adequate major organ function, except for local compression or functional impairment directly attributable to nasopharyngeal carcinoma.
  11. Good expected compliance with follow-up and reliable communication conditions, allowing completion of long-term survival follow-up.

Exclusion Criteria

  1. 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.
  2. Presence of distant metastatic disease, M1.
  3. 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.
  4. Pregnant or breastfeeding women, or participants of reproductive potential who are unwilling to use effective contraception during the study observation period.
  5. Current participation in another interventional clinical trial involving an investigational drug or medical device.
  6. 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.
  7. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Administered intravenously every 3 weeks for up to 12 cycles as adjuvant therapy.
Drug: Capecitabine
Metronomic capecitabine administered orally at a dose of 650 mg/m2 twice daily for one year as adjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
3-year Failure-Free Survival (FFS)
Time Frame: Up to 3 years
FFS is defined as the time from enrollment to locoregional recurrence, distant metastasis, or death from any cause.
Up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Acute and Late Toxicities and Adverse Events
Time Frame: From the start of treatment up to 3 years
Adverse events will be evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
From the start of treatment up to 3 years
Complete Response (CR) Rate after Chemoradiotherapy
Time Frame: 1 month after the completion of radiotherapy
Proportion of patients achieving a complete response after the completion of concurrent chemoradiotherapy.
1 month after the completion of radiotherapy
3-year Overall Survival (OS)
Time Frame: Up to 3 years
OS is defined as the time from enrollment to death from any cause.
Up to 3 years
3-year Locoregional Relapse-Free Survival (LRRFS)
Time Frame: Up to 3 years
LRRFS is defined as the time from enrollment to the first locoregional recurrence or death from any cause.
Up to 3 years
3-year Distant Metastasis-Free Survival (DMFS)
Time Frame: Up to 3 years
DMFS is defined as the time from enrollment to the first distant metastasis or death from any cause.
Up to 3 years
Longitudinal Changes in EORTC QLQ-C30 Scores
Time Frame: From baseline to 36 months after enrollment
Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, version 3.0. All scale and single-item scores are linearly transformed to a 0 to 100 scale. For the global health status/quality-of-life scale and functional scales, higher scores indicate better global health status, quality of life, or functioning. For symptom scales and single-item symptom measures, higher scores indicate worse symptoms or greater problems.
From baseline to 36 months after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Xijing Hospital
Xiangya Hospital of Central South University
Fujian Cancer Hospital
Hunan Cancer Hospital
Peking University Cancer Hospital & Institute
Cancer Hospital of Guizhou Province
Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
Sun Yat-Sen University Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Junlin Yi, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 25, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 1, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 26/007-5732

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Data will be available beginning 6 months following article publication.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Nasopharyngeal Carcinoma (NPC)

Clinical Trials on PD-1 inhibitor

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings