Individualized Neck Cervical Irradiation Prophylaxis Trial of NPC

NCT07303023 | Recruiting Phase 3 DMC

• 2 other identifiers: INCIPT-NPC2507-83-01
• Study Type: interventional
• Target: 462
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

IMRT; carbon ion radiotherapy; Prophylactic Neck Irradiation

Outcome Measures

Primary Outcomes (1)

• neck recurrence-free survival.

  3-year neck recurrence-free survival.

Secondary Outcomes (4)

• overall survival

  3-year

• local recurrence-free survival

  3-years

• Locoregional Recurrence-Free Survival

  3 years

• Distant Metastasis-Free Survival

  3 years

Other Outcomes (1)

• incidence of acute and late neck radiation-induced injuries

  3-year

Study Arms (2)

investigational arm

EXPERIMENTAL

Radiation: Individualized Neck Irradiation

control arm

ACTIVE COMPARATOR

Standard Neck Irradiation

Radiation: Standard Neck Irradiation

Interventions

Individualized Neck Irradiation RADIATION

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.

investigational arm

Standard Neck Irradiation RADIATION

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.

control arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years.
• Pathologically confirmed WHO type I, II, or III nasopharyngeal carcinoma.
• Staged as T1-4N0-3 M0, Stage I-III according to the UICC/AJCC 9th edition staging system.
• Absence of distant metastasis confirmed by systemic FDG PET/CT (or whole-body bone scan plus chest CT and abdominal ultrasound).
• Ability to undergo MRI examination.
• Adequate major organ function meeting radiotherapy requirements:
• Hematopoietic function: Hemoglobin ≥9 g/L, Platelets ≥100×10⁹/L, WBC ≥3.5×10⁹/L, Neutrophils ≥2.0×10⁹/L.
• Liver function: ALT and AST \< 2.5 × ULN, Bilirubin \< 1.5 × ULN.
• Renal function: Creatinine clearance ≥50 mL/min or serum creatinine within normal range.
• Patients with clinical symptoms will be evaluated based on specific manifestations.
• 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).
• Life expectancy ≥12 months.
• Patients must be informed of the study details and provide written informed consent.

You may not qualify if:

• Pathology not confirming WHO type I, II, or III nasopharyngeal carcinoma.
• Distant metastasis identified clinically or radiologically before treatment, or presence of skip metastases in cervical lymph nodes.
• Pregnancy (confirmed by serum or urine β-HCG test) or lactation.
• Unwillingness to provide informed consent.
• Prior radiotherapy to the head and neck region.
• Comorbidities or other factors that may contraindicate photon or carbon-ion therapy.
• Inability to comply with regular follow-up due to psychological, social, familial, or geographical reasons.
• Known allergy to chemotherapeutic agents (e.g., cisplatin, docetaxel, gemcitabine) or contrast media used in the study's imaging examinations.
• Contraindication to contrast-enhanced MRI.
• Major organ dysfunction, or severe uncontrolled concurrent infection or medical illness (e.g., decompensated cardiac, pulmonary, renal, or hepatic failure).
• History of immunodeficiency (positive HIV test), other acquired/congenital immunodeficiency disorders, or history of organ/allogeneic bone marrow transplantation.
• History of other malignancies prior to enrollment (except for basal cell carcinoma of the skin).
• History of substance or alcohol abuse.
• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (6)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Eye, Ear, Nose and Throat Hospital of Fudan University

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

NOT YET RECRUITING

Sichuan Cancer Hospital & Institute

Chengdu, China

NOT YET RECRUITING

Chongqing Cancer Hospital

Chongqing, China

NOT YET RECRUITING

Shanghai Proton and Heavy Ion Center

Shanghai, China

RECRUITING

Related Publications (13)

• Zhu GL, Zhang XM, Yang KB, Tang LL, Ma J. Metastatic patterns of level II-V cervical lymph nodes assessed per vertebral levels in nasopharyngeal carcinoma. Radiother Oncol. 2023 Feb;179:109447. doi: 10.1016/j.radonc.2022.109447. Epub 2022 Dec 19.

  PMID: 36549338 RESULT

• Liu Y, Han Y, Liu F, Hu D, Chen Z, Wang P, Li J, Qin J, Jin F, Li Y, Wang J, Yi J. Involved site radiation therapy in stage I-III nasopharyngeal carcinoma with limited lymph node burden (ISRT-NPC) or elective region irradiation: a study protocol for a multicenter non-inferiority randomized controlled phase III clinical trial. BMC Cancer. 2023 Aug 3;23(1):724. doi: 10.1186/s12885-023-11212-7.

  PMID: 37537541 RESULT

• Liu Y, Yan W, Hu C, Huang X, Wang K, Qu Y, Chen X, Wu R, Zhang Y, Zhang J, Luo J, Li Y, Wang J, Yi J. Optimizing Cervical Target Volume in Patients with Nasopharyngeal Cancer Based On Nodal Drainage Distance. Clin Cancer Res. 2024 May 1;30(9):1801-1810. doi: 10.1158/1078-0432.CCR-23-3274.

  PMID: 38349999 RESULT

• Wang L, Wu Z, He Q, Li Y, Wang S, Li F, Wang H, Li W, Han Y. Distribution of regional lymph nodes metastasis in 870 cases of nasopharyngeal carcinoma and the suggestions for individualized elective prophylactic neck irradiation with intensity-modulated radiotherapy. Cancer Med. 2024 Feb;13(3):e6723. doi: 10.1002/cam4.6723. Epub 2023 Dec 29.

  PMID: 38156901 RESULT

• Xie DH, Wu Z, Li WZ, Cheng WQ, Tao YL, Wang L, Lv SW, Lin FF, Cui NJ, Zhao C, Ma J, Huang SM, Lu TX, Han YQ, Su Y. Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary. J Cancer Res Clin Oncol. 2022 Aug;148(8):1931-1942. doi: 10.1007/s00432-022-03974-7. Epub 2022 Apr 29.

  PMID: 35486182 RESULT

• Wu Z, Qi B, Lin FF, Zhang L, He Q, Li FP, Wang H, Han YQ, Yin WJ. Characteristics of local extension based on tumor distribution in nasopharyngeal carcinoma and proposed clinical target volume delineation. Radiother Oncol. 2023 Jun;183:109595. doi: 10.1016/j.radonc.2023.109595. Epub 2023 Mar 3.

  PMID: 36870606 RESULT

• Tang LL, Chen L, Xu GQ, Zhang N, Huang CL, Li WF, Mao YP, Zhou GQ, Lei F, Chen LS, Huang SH, Chen L, Chen YP, Zhang Y, Liu X, Xu C, Zhao Y, Li JB, Liu N, Xie FY, Guo R, Sun Y, Ma J. Reduced-volume radiotherapy versus conventional-volume radiotherapy after induction chemotherapy in nasopharyngeal carcinoma: An open-label, noninferiority, multicenter, randomized phase 3 trial. CA Cancer J Clin. 2025 May-Jun;75(3):203-215. doi: 10.3322/caac.21881. Epub 2025 Feb 19.

  PMID: 39970442 RESULT

• Huang CL, Zhang N, Jiang W, Xie FY, Pei XQ, Huang SH, Wang XY, Mao YP, Li KP, Liu Q, Li JB, Liang SQ, Qin GJ, Hu WH, Zhou GQ, Ma J, Sun Y, Chen L, Tang LL. Reduced-Volume Irradiation of Uninvolved Neck in Patients With Nasopharyngeal Cancer: Updated Results From an Open-Label, Noninferiority, Multicenter, Randomized Phase III Trial. J Clin Oncol. 2024 Jun 10;42(17):2021-2025. doi: 10.1200/JCO.23.02086. Epub 2024 Mar 20.

  PMID: 38507662 RESULT

• Lin SJ, Guo QJ, Liu Q, Ng WT, Ahn YC, AlHussain H, Chan AW, Chow J, Chua MLK, Corry J, Han F, Gregoire V, Harrington KJ, Hu CS, Jensen K, Langendijk JA, Le QT, Lee NY, Lee V, Lin JC, Ma J, Mendenhall WM, O'Sullivan B, Ozyar E, Rosenthal DI, Tao YG, Wang RS, Wee J, Xu ZY, Yi JL, Yom SS, Fan DM, Mai HQ, Pan JJ, Lee AWM. International Consensus Guideline on Delineation of the Clinical Target Volumes at Different Dose Levels for Nasopharyngeal Carcinoma (2024 Version). Int J Radiat Oncol Biol Phys. 2025 Oct 1;123(2):415-431. doi: 10.1016/j.ijrobp.2025.05.019. Epub 2025 May 24.

  PMID: 40419028 RESULT

• Pan JJ, Mai HQ, Ng WT, Hu CS, Li JG, Chen XZ, Chow JCH, Wong E, Lee V, Ma LY, Guo QJ, Liu Q, Liu LZ, Xu TT, Gong XC, Qiang MY, Au KH, Liu TC, Chiang CL, Xiao YP, Lin SJ, Chen YB, Guo SS, Wong CHL, Tang LQ, Xu ZY, Jia YZ, Peng WS, Hu LP, Lu TZ, Jiang F, Cao CN, Xu W, Ma J, Blanchard P, Williams M, Glastonbury CM, King AD, Patel SG, Seethala RR, Colevas AD, Fan DM, Chua MLK, Huang SH, O'Sullivan B, Lydiatt W, Lee AWM. Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification. JAMA Oncol. 2024 Oct 10;10(12):1627-35. doi: 10.1001/jamaoncol.2024.4354. Online ahead of print.

  PMID: 39388190 RESULT

• Lee AW, Ng WT, Pan JJ, Chiang CL, Poh SS, Choi HC, Ahn YC, AlHussain H, Corry J, Grau C, Gregoire V, Harrington KJ, Hu CS, Kwong DL, Langendijk JA, Le QT, Lee NY, Lin JC, Lu TX, Mendenhall WM, O'Sullivan B, Ozyar E, Peters LJ, Rosenthal DI, Sanguineti G, Soong YL, Tao Y, Yom SS, Wee JT. International Guideline on Dose Prioritization and Acceptance Criteria in Radiation Therapy Planning for Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2019 Nov 1;105(3):567-580. doi: 10.1016/j.ijrobp.2019.06.2540. Epub 2019 Jul 2.

  PMID: 31276776 RESULT

• Lee AW, Ng WT, Pan JJ, Poh SS, Ahn YC, AlHussain H, Corry J, Grau C, Gregoire V, Harrington KJ, Hu CS, Kwong DL, Langendijk JA, Le QT, Lee NY, Lin JC, Lu TX, Mendenhall WM, O'Sullivan B, Ozyar E, Peters LJ, Rosenthal DI, Soong YL, Tao Y, Yom SS, Wee JT. International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma. Radiother Oncol. 2018 Jan;126(1):25-36. doi: 10.1016/j.radonc.2017.10.032. Epub 2017 Nov 15.

  PMID: 29153464 RESULT

• Tang LL, Chen YP, Chen CB, Chen MY, Chen NY, Chen XZ, Du XJ, Fang WF, Feng M, Gao J, Han F, He X, Hu CS, Hu DS, Hu GY, Jiang H, Jiang W, Jin F, Lang JY, Li JG, Lin SJ, Liu X, Liu QF, Ma L, Mai HQ, Qin JY, Shen LF, Sun Y, Wang PG, Wang RS, Wang RZ, Wang XS, Wang Y, Wu H, Xia YF, Xiao SW, Yang KY, Yi JL, Zhu XD, Ma J. The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma. Cancer Commun (Lond). 2021 Nov;41(11):1195-1227. doi: 10.1002/cac2.12218. Epub 2021 Oct 26.

  PMID: 34699681 RESULT

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

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

Central Study Contacts

Xiyin Guan, MD. PhD.

CONTACT

+86-15921292432; forrestguan@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: MD. PhD.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 24, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2031
• Last Updated: December 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

CN (6)