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

August 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 to evaluate whether primary clinical target volume (CTVp) delineation based on margin expansion provides comparable outcomes compared with the consensus CTVp approach based on margin expansion and the stepwise extension pattern in newly diagnosed non-metastatic nasopharyngeal carcinoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This multicenter, prospective, randomized phase 3 trial aims to evaluate a margin-expansion-based primary clinical target volume (CTVp) delineation strategy in patients with newly diagnosed non-metastatic nasopharyngeal carcinoma (NPC). The primary objective is to demonstrate non-inferiority of this CTVp approach compared with the consensus CTVp defined by the CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines (which incorporate both margin expansion and local stepwise extension patterns), with local relapse-free survival as the primary endpoint. Secondary objectives include comparisons of overall survival, failure-free survival, distant metastasis-free survival, locoregional relapse-free survival, and regional relapse-free survival between the two CTVp strategies, as well as assessments of radiotherapy-related complications, quality of life, and their impact on the tumor immune microenvironment, along with exploration of the underlying biological mechanisms.

Eligible patients will be prospectively enrolled from multiple centers across China and randomized in a 1:1 ratio to receive either the margin-based CTVp or the consensus guideline-based CTVp. Comprehensive treatment in both arms will follow current clinical guidelines and be stratified by tumor stage. Prognosis, toxicity, and quality-of-life outcomes will be systematically compared between the two groups.

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
        • Not yet recruiting
        • Dongguan People's Hospital
        • Contact:
        • Principal Investigator:
          • Zhi-Gang Liu, Prof.
      • Foshan, Guangdong, China, 528000
        • Not yet recruiting
        • First People's Hospital of Foshan
        • Contact:
          • Gui-Chao Liu, Dr.
        • Principal Investigator:
          • Gui-Chao Liu, Dr.
      • Guangzhou, Guangdong, China
      • Shenzhen, Guangdong, China, 518116
        • Not yet recruiting
        • Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen
        • Contact:
        • Principal Investigator:
          • Yan-Ling Wu, Dr.
        • Sub-Investigator:
          • Jiang-Hu Zhang, Dr.
      • Zhongshan, Guangdong, China, 528400
        • Not yet recruiting
        • Zhongshan City People's Hospital
        • Contact:
        • Principal Investigator:
          • Gui-Qiong Xu
    • Hunan
      • Changsha, Hunan, China
        • Not yet recruiting
        • Xiangya Hospital Central South University
        • Contact:
        • Principal Investigator:
          • Liang-Fang Shen, Prof.
      • Changsha, Hunan, China
        • Not yet recruiting
        • Hunan Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Ya-Qian Han, Prof.

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
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: ① Induction Chemotherapy (GP Regimen) + Concurrent Chemoradiotherapy (Cisplatin); ② Induction Chemoimmunotherapy (GP Regimen + PD-1 Monoclonal Antibody) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody); ③ Induction Chemotherapy (GP Regimen) + 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.
Experimental: 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: ① Induction Chemotherapy (GP Regimen) + Concurrent Chemoradiotherapy (Cisplatin); ② Induction Chemoimmunotherapy (GP Regimen + PD-1 Monoclonal Antibody) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody); ③ Induction Chemotherapy (GP Regimen) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody).
Radiation: IMRT with 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local relapse-free survival (LRFS)
Time Frame: 3 years
Local relapse-free survival is estimated from randomisation to documented local relapse or death.
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.
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.
Overall survival (OS)
Time Frame: 3 years
Overall survival is measured from the date of randomisation until death from any cause.
3 years
Failure-free survival (FFS)
Time Frame: 3 years
Failure-free survival is measured from the date of randomisation until local recurrence, regional recurrence, distant failure, or death from any cause, whichever occurs first.
3 years
Distant metastasis-free survival (DMFS)
Time Frame: 3 years
Distant metastasis-free survival is calculated from randomisation to documented distant metastasis or death.
3 years
Locoregional relapse-free survival (LRFFS)
Time Frame: 3 years
Locoregional relapse-free survival is measured from the date of randomisation until local or regional recurrence or death.
3 years
Regional relapse-free survival (RRFS)
Time Frame: 3 years
Regional relapse-free survival is defined as the time from randomisation to documented nodal relapse or death.
3 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 (Actual)

July 24, 2026

Primary Completion (Estimated)

July 30, 2029

Study Completion (Estimated)

July 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)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 16, 2026

Last Verified

July 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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