Individualized Primary Clinical Target Volume Based on Margin Expansion for Nasopharyngeal Carcinoma (CTV-MARGIN-NPC)

June 16, 2026 updated by: Jun Ma, MD, Sun Yat-sen University

Individualized Primary Clinical Target Volume Based on Margin Expansion for Nasopharyngeal Carcinoma: A Non-Inferiority, Multicenter, Randomized Phase 3 Trial

This is a non-inferiority, multicenter, randomized phase 3 trial aimed at investigating the impact of individualized primary clinical target volume based on margin expansion on patients' prognosis and complications compared with the consensus primary clinical target volume based on margin expansion and stepwise extension pattern for patients with newly diagnosed non-metastatic nasopharyngeal carcinoma.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The goals of this clinical trial are: a) To confirm whether the local failure-free survival of patients with nasopharyngeal carcinoma whose primary clinical target volume is delineated based on margin expansion is non-inferior to the local failure-free survival of patients whose primary clinical target volume is delineated according to the CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas; b) To explore the impact of the individualized primary clinical target volume based on margin expansion on the overall survival, failure-free survival, distant failure-free survival, locoregional failure-free survival, and regional failure-free survival of patients with nasopharyngeal carcinoma; c) To explore the impact of the individualized primary clinical target volume based on margin expansion on radiotherapy-related complications and quality of life; d) To explore the impact of the individualized primary clinical target volume based on margin expansion on the tumor immune microenvironment, along with its underlying biological mechanisms.

For these purposes, we plan to prospectively enroll patients with newly diagnosed non-metastatic nasopharyngeal carcinoma from hospitals in China. The participants will be randomized into the experimental group and the control group. Comprehensive therapy for participants in both groups will be designed based on tumor stage according to the current clinical guidelines for the management of nasopharyngeal carcinoma. During the radiotherapy, the primary clinical target volume will be delineated based on margin expansion for the experimental group, while the primary clinical target volume will be delineated based on margin expansion and local stepwise extension patterns according to the CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas for the control group. The prognosis, complications, and quality of life will be compared between the experimental group and the control group.

Study Type

Interventional

Enrollment (Estimated)

568

Phase

  • Phase 3

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 Backup

Study Locations

  • China
    • Guangdong
      • Dongguan, Guangdong, China
      • Guangzhou, Guangdong, China
    • Hunan
      • Changsha, Hunan, China
        • Hunan Cancer Hospital
        • Contact:
      • Changsha, Hunan, China
        • Xiangya Hospital Central South University
        • 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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age: 18 Years to 65 Years.
  2. Eastern Cooperative Oncology Group performance status ≤1.
  3. Patients with newly diagnosed, histologically confirmed nasopharyngeal carcinoma (non-keratinizing subtype).
  4. Tumor staged as T1-4N0-3M0 (AJCC 9th).
  5. Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule.
  6. Women of childbearing potential and male subjects with female partners of childbearing potential must agree to use reliable contraceptive measures from screening to 1 year after treatment.

  7. For subjects requiring chemotherapy, the following are additionally required:

    1. normal bone marrow function (white blood cell count > 4 × 10^9/L, hemoglobin > 90 g/L, platelet count > 100 × 10^9/L);
    2. normal liver and kidney function (total bilirubin ≤ 1.5 × upper limit of normal, alanine transaminase and aspartate transaminase ≤ 2.5 × upper limit of normal, alkaline phosphatase ≤ 2.5 × upper limit of normal, creatinine clearance rate ≥ 60 mL/min).

Exclusion Criteria:

  1. Active tuberculosis: active tuberculosis within the past 1 year should be excluded regardless of treatment; a history of active tuberculosis > 1 year ago is exclusionary unless prior adequate anti-tuberculosis treatment is documented.
  2. Active infection requiring systemic treatment.
  3. Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer.
  4. History of radiotherapy, except for non-melanoma skin cancer located outside the target volume of radiotherapy for nasophayngeal carcinoma.
  5. Prior or concurrent treatment for local or regional disease other than that specified in the research plan.
  6. Pregnant or lactating women (a pregnancy test is required for women of childbearing potential).
  7. Contraindications to MRI examination, for example: claustrophobia, allergy to MRI contrast.
  8. History of psychiatric disorders, alcoholism or drug abuse, and other situations assessed by the investigators that may compromise the safety or compliance of patients, such as serious disease requiring timely treatment (including mental illness), severe laboratory abnormalities, or family-social risk factors.

  9. For participants requiring chemotherapy, the following must also be excluded:

    1. anti-human immunodeficiency virus positive or diagnosed with acquired immune deficiency syndrome;
    2. uncontrolled heart disease (heart failure [NYHA Class ≥ 2], unstable angina, myocardial infarction in past 1 year, supraventricular or ventricular arrhythmia requiring treatment or intervention).

  10. For participants requiring immunotherapy, the following must also be excluded:

    1. hepatitis B virus surface antigen positive and Hepatitis B virus DNA > 1000 copies/mL;
    2. anti-hepatitis C virus positive;
    3. active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary disease, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchodilators, exceptions are type I diabetes mellitus, hypothyroidism not requiring hormone replacement therapy, skin disorders not requiring systemic treatment [such as vitiligo, psoriasis or alopecia]);
    4. previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
    5. chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day, subjects who use inhaled or topical corticosteroids are eligible) or any other form of immunosuppressive therapy;
    6. allergy to macromolecular protein preparations, or any component of PD-1 monoclonal antibody;
    7. receiving live vaccine within 30 days prior to the first dose of PD-1 monoclonal antibody.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Individualized Primary Clinical Target Volume Based on Margin Expansion
During radiotherapy, the clinical target volume for the primary tumor will be delineated based on margin expansion.
Procedure: Comprehensive Therapy Based on Tumor Stage
  1. T1N0: Radiotherapy Only.
  2. T1N1, T2N0-1, T3N0: Radiotherapy with or without Concurrent Chemotherapy (Cisplatin).
  3. T3N1, T4N0: Concurrent Chemoradiotherapy (Cisplatin) with or without Induction Chemotherapy (GP Regimen).
  4. T1-4N2-3, T4N1: Induction Chemoimmunotherapy (GP Regimen + PD-1 Monoclonal Antibody) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody).
Radiation: IMRT with Individualized Primary Clinical Target Volume Based on Margin Expansion

  1. Target delineation:

    1. CTVp_High = GTVp + 0 mm
    2. CTVp_Mid = CTVp_High + 5 mm
    3. CTVp_Low = CTVp_Mid + 5 mm + whole nasopharynx
    4. CTVn_High = GTVn + 0 mm
    5. CTVn_Mid = CTVn_High + 3-5 mm (for nodes with imaging-detected extranodal extension) or 0 mm (for nodes without imaging-detected extranodal extension) + equivocal nodes in the anticipated drainage levels, close proximity to enlarged nodes, or with suspicious PET results
    6. CTVn_Low = CTVn_Mid + 3 mm + elective drainage levels

  2. Dose prescription:

    1. 6996 cGy/33 fx for CTVp_High and CTVn_High
    2. 6006 cGy/33 fx for CTVp_Mid and CTVn_Mid
    3. 5412 cGy/33 fx for CTVp_Low and CTVn_Low
Active Comparator: Consensus Primary Clinical Target Volume Based on Margin Expansion and Stepwise Extension Pattern
During radiotherapy, the clinical target volume for the primary tumor will be delineated based on margin expansion and local stepwise extension patterns according to the CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.
Procedure: Comprehensive Therapy Based on Tumor Stage
  1. T1N0: Radiotherapy Only.
  2. T1N1, T2N0-1, T3N0: Radiotherapy with or without Concurrent Chemotherapy (Cisplatin).
  3. T3N1, T4N0: Concurrent Chemoradiotherapy (Cisplatin) with or without Induction Chemotherapy (GP Regimen).
  4. T1-4N2-3, T4N1: Induction Chemoimmunotherapy (GP Regimen + PD-1 Monoclonal Antibody) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody).
Radiation: IMRT with Consensus Primary Clinical Target Volume

  1. Target delineation:

    1. CTVp_High = GTVp + 0 mm
    2. CTVp_Mid = CTVp_High + 5 mm
    3. CTVp_Low = CTVp_Mid + 5 mm + whole nasopharynx + high-risk structures based on stepwise local extension patterns of tumor spread
    4. CTVn_High = GTVn + 0 mm
    5. CTVn_Mid = CTVn_High + 3-5 mm (for nodes with imaging-detected extranodal extension) or 0 mm (for nodes without imaging-detected extranodal extension) + equivocal nodes in the anticipated drainage levels, close proximity to enlarged nodes, or with suspicious PET results
    6. CTVn_Low = CTVn_Mid + 3 mm + elective drainage levels

  2. Dose prescription:

    1. 6996 cGy/33 fx for CTVp_High and CTVn_High
    2. 6006 cGy/33 fx for CTVp_Mid and CTVn_Mid
    3. 5412 cGy/33 fx for CTVp_Low and CTVn_Low

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local failure-free survival (LFFS)
Time Frame: 3 years
Local failure-free survival is measured from the date of diagnosis until local recurrence.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence rate of investigator-reported radiotherapy-related complications
Time Frame: Within (acute complication) / since (late complication) 90 days after the radiotherapy onset.
Within (acute complication) / since (late complication) 90 days after the radiotherapy onset.
Overall survival (OS)
Time Frame: 3 years
Overall survival is measured from the date of diagnosis until death from any cause.
3 years
Failure-free survival (FFS)
Time Frame: 3 years
Failure-free survival is measured from the date of diagnosis until local recurrence, regional recurrence, distant failure, or death from any cause, whichever occurs first.
3 years
Distant failure-free survival (DFFS)
Time Frame: 3 years
Distant failure-free survival is measured from the date of diagnosis until distant failure.
3 years
Locoregional failure-free survival (LRFFS)
Time Frame: 3 years
Locoregional failure-free survival is measured from the date of diagnosis until local or regional recurrence.
3 years
Regional failure-free survival (RFFS)
Time Frame: 3 years
Regional failure-free survival is measured from the date of diagnosis until regional recurrence.
3 years
Incidence rate of patient-reported adverse events
Time Frame: Periprocedural.
Periprocedural.
Quality of life (QoL): questionnaire
Time Frame: Up to 5 years.
Up to 5 years.

Collaborators and Investigators

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

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Jun Ma, Prof., Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

July 1, 2026

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

June 30, 2034

Study Registration Dates

First Submitted

June 10, 2026

First Submitted That Met QC Criteria

June 16, 2026

First Posted (Actual)

June 22, 2026

Study Record Updates

Last Update Posted (Actual)

June 22, 2026

Last Update Submitted That Met QC Criteria

June 16, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-FXY-200-FLK

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

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