Individualized Neck Cervical Irradiation Prophylaxis Trial of NPC (INCIPT-NPC)

December 18, 2025 updated by: Chaosu Hu, Fudan University

Individualized Versus Standard Neck Prophylactic Irradiation in Nasopharyngeal Carcinoma: A Non-inferiority, Phase III, Multicenter, Prospective, Randomized Controlled Trial

Based on the pattern of nasopharyngeal carcinoma cervical lymph node metastasis, which typically follows a sequential downward spread with rare skip metastases and a tendency for ipsilateral neck involvement, and in accordance with the latest international guidelines, we propose the following scientific hypothesis: individualized neck prophylactic irradiation for nasopharyngeal carcinoma based on the superior-to-inferior extent of metastatic lymph nodes is feasible. Specifically: if there is no lymph node metastasis, irradiation need only extend to the lower border of Level II; if there are suspected metastatic lymph nodes, a prophylactic dose of 55-60 Gy should be administered; the investigational arm will only require irradiation extending to 3 cm below the lowest level of metastatic (including suspected) lymph nodes in each neck.This study will prospectively enroll patients with N0-N3 stage nasopharyngeal carcinoma and randomize them to compare individualized neck irradiation based on the vertebral body level of metastatic lymph nodes versus selective upper neck prophylactic irradiation. The primary endpoint is neck recurrence-free survival. Secondary endpoints include overall survival, local recurrence-free survival and other survival data, incidence of acute and late neck radiation-induced injuries, and quality of life, aiming to validate the feasibility of individualized neck irradiation based on metastatic patterns.Photon IMRT and photon plus carbon-ion radiotherapy will serve as stratification factors, enabling further comparison of local control and toxicity between photon-carbon-ion therapy and photon-only (or proton) therapy. This study seeks to protect critical structures such as the thyroid, trachea, esophagus, and neck muscles while maintaining therapeutic efficacy, ultimately improving the quality of life for nasopharyngeal carcinoma patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a multicenter, prospective, non-inferiority, open-label, phase III randomized controlled clinical trial. A total of 462 patients will be enrolled, with an anticipated accrual period of three years and a follow-up period of three years post-enrollment.

Eligible patients will have newly diagnosed, non-metastatic nasopharyngeal carcinoma, staged as T1-4N0-3M0, Stage I-III according to the UICC/AJCC 9th edition staging system. After confirmation of the radiotherapy technique, patients will be randomized. Patients in the investigational arm will receive bilateral upper neck irradiation covering at least Level II. If cervical lymph nodes are positive, the clinical target volume (CTV) will extend to 3 cm below the lowest level of metastatic (including suspected) lymph nodes. Patients in the control arm will receive bilateral upper neck irradiation; if upper neck nodes are positive, prophylactic irradiation of the lower neck will be performed. Primary tumor and nodal CTV delineation for both arms will adhere to the 2024 international contouring guidelines for nasopharyngeal carcinoma.

Photon IMRT alone or photon IMRT plus carbon-ion radiotherapy will serve as stratification factors. The prescribed doses for photon IMRT alone are as follows: GTVp and GTVn: 66-70.4 Gy in 30-33 fractions; high-risk CTV1: 60 Gy in 30-33 fractions; low-risk CTV2: 50 Gy in 30-33 fractions. For the combined photon IMRT and carbon-ion radiotherapy arm, the prescription doses are: Photon IMRT - GTVp and GTVn: 55 Gy in 25 fractions; high-risk CTV1: 55 Gy in 25 fractions; low-risk CTV2: 50 Gy in 25 fractions. Carbon-ion boost - GTVp and GTVn: 15-18 Gy (RBE) in 6 fractions.

If indicated, patients will receive induction chemotherapy with the GP regimen (Gemcitabine 1000 mg/m² on Day 1 and Day 8, plus Cisplatin 75 mg/m² divided over three days) for 2-3 cycles. Concurrent chemotherapy, if administered, will consist of Cisplatin 80 mg/m² divided over three days, given every 3 weeks for 2 cycles.

Tumor response will be assessed by EBV-DNA levels and MRI at the end of induction chemotherapy, at the end of concurrent chemoradiotherapy, and three months after treatment completion. Follow-up visits will be scheduled every three months for the first two years post-treatment. Subsequent follow-up will be conducted as per protocol. Quality of life questionnaires, as specified by the study, will be completed before treatment, after treatment completion, and during the follow-up period.

Study Type

Interventional

Enrollment (Estimated)

462

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 Locations

  • China
      • Chengdu, China
        • Not yet recruiting
        • Sichuan Cancer Hospital & Institute
        • Contact:
      • Chongqing, China
        • Not yet recruiting
        • Chongqing Cancer Hospital
        • Contact:
      • Shanghai, China
        • Recruiting
        • Shanghai Proton and Heavy Ion Center
        • Contact:
        • Contact:
          • Xing Xing
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
      • Shanghai, Shanghai Municipality, China
        • Not yet recruiting
        • Eye, Ear, Nose and Throat Hospital of Fudan University
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Not yet recruiting
        • Zhejiang Cancer Hospital
        • 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

Yes

Description

Inclusion Criteria:

  1. Age 18-70 years.
  2. Pathologically confirmed WHO type I, II, or III nasopharyngeal carcinoma.
  3. Staged as T1-4N0-3 M0, Stage I-III according to the UICC/AJCC 9th edition staging system.
  4. Absence of distant metastasis confirmed by systemic FDG PET/CT (or whole-body bone scan plus chest CT and abdominal ultrasound).
  5. Ability to undergo MRI examination.

  6. Adequate major organ function meeting radiotherapy requirements:

    1. Hematopoietic function: Hemoglobin ≥9 g/L, Platelets ≥100×10⁹/L, WBC ≥3.5×10⁹/L, Neutrophils ≥2.0×10⁹/L.
    2. Liver function: ALT and AST < 2.5 × ULN, Bilirubin < 1.5 × ULN.
    3. Renal function: Creatinine clearance ≥50 mL/min or serum creatinine within normal range.
    4. Patients with clinical symptoms will be evaluated based on specific manifestations.
  7. ECOG performance status 0-1; absence of severe comorbidities (e.g., severe pulmonary hypertension, cardiovascular disease, peripheral vascular disease, severe chronic heart disease) that may preclude radiotherapy. Cardiac function class 1-2 (NYHA classification).
  8. Life expectancy ≥12 months.
  9. Patients must be informed of the study details and provide written informed consent.

Exclusion Criteria:

  1. Pathology not confirming WHO type I, II, or III nasopharyngeal carcinoma.
  2. Distant metastasis identified clinically or radiologically before treatment, or presence of skip metastases in cervical lymph nodes.
  3. Pregnancy (confirmed by serum or urine β-HCG test) or lactation.
  4. Unwillingness to provide informed consent.
  5. Prior radiotherapy to the head and neck region.
  6. Comorbidities or other factors that may contraindicate photon or carbon-ion therapy.
  7. Inability to comply with regular follow-up due to psychological, social, familial, or geographical reasons.
  8. Known allergy to chemotherapeutic agents (e.g., cisplatin, docetaxel, gemcitabine) or contrast media used in the study's imaging examinations.
  9. Contraindication to contrast-enhanced MRI.
  10. Major organ dysfunction, or severe uncontrolled concurrent infection or medical illness (e.g., decompensated cardiac, pulmonary, renal, or hepatic failure).
  11. History of immunodeficiency (positive HIV test), other acquired/congenital immunodeficiency disorders, or history of organ/allogeneic bone marrow transplantation.
  12. History of other malignancies prior to enrollment (except for basal cell carcinoma of the skin).
  13. History of substance or alcohol abuse.
  14. Any other condition deemed by the investigator to potentially lead to study discontinuation, including co-morbidities (including psychiatric) requiring concomitant treatment, severely abnormal laboratory values, or familial/social factors compromising patient safety or data integrity.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: investigational arm
Radiation: Individualized Neck Irradiation
After confirmation of the radiotherapy technique, patients will be randomized. Patients in the investigational arm will receive bilateral upper neck irradiation covering at least Level II. If cervical lymph nodes are positive, the clinical target volume (CTV) will extend to 3 cm below the lowest level of metastatic (including suspected) lymph nodes.
Active Comparator: control arm
Standard Neck Irradiation
Radiation: Standard Neck Irradiation
Patients in the control arm will receive bilateral upper neck irradiation to level III; if upper neck nodes are positive, prophylactic irradiation of the lower neck will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
neck recurrence-free survival.
Time Frame: 3-year neck recurrence-free survival.
3-year neck recurrence-free survival.

Secondary Outcome Measures

Outcome Measure
Time Frame
overall survival
Time Frame: 3-year
3-year
local recurrence-free survival
Time Frame: 3-years
3-years
Locoregional Recurrence-Free Survival
Time Frame: 3 years
3 years
Distant Metastasis-Free Survival
Time Frame: 3 years
3 years

Other Outcome Measures

Outcome Measure
Time Frame
incidence of acute and late neck radiation-induced injuries
Time Frame: 3-year
3-year

Collaborators and Investigators

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

Sponsor

Fudan 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)

September 1, 2025

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2031

Study Registration Dates

First Submitted

November 14, 2025

First Submitted That Met QC Criteria

December 18, 2025

First Posted (Actual)

December 24, 2025

Study Record Updates

Last Update Posted (Actual)

December 24, 2025

Last Update Submitted That Met QC Criteria

December 18, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INCIPT-NPC
  • 2507-83-01 (Registry Identifier: Shanghai Proton and Heavy Ion Center Institutional Review Board)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • CSR

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.

Clinical Trials on Nasopharyngeal Carcinoma (NPC)

Clinical Trials on Individualized Neck Irradiation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe