Phase III Non-Inferiority Trial of Proton Versus Photon Therapy for Nasopharyngeal Carcinoma

NCT07000643 | Recruiting Phase 3

• 1 other identifier: SDZLEC2025-067-01
• Study Type: interventional
• Target: 386
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, open-label, multicenter, cohort, phase III non-inferiority clinical trial comparing proton therapy with photon radiotherapy for nasopharyngeal carcinoma. It intends to enroll histologically confirmed newly diagnosed nasopharyngeal carcinoma patients without distant metastasis (M0). Through a prospective 1:1 matched cohort study design, patients will be divided into the intensity-modulated proton therapy (IMPT) group and the intensity-modulated radiation therapy (IMRT) group. Systemic treatment regimens are formulated according to clinical guidelines.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal carcinoma; proton radiotherapy; target area delineation

Outcome Measures

Primary Outcomes (1)

• 2-year Locoregional Recurrence-Free Survival (LRFS)

  Defined as the time from group allocation to local-regional recurrence, including recurrence at the primary site and lymph node regions, or death from any cause.

  2 years

Secondary Outcomes (5)

• 2-year Overall Survival (OS)

  2 years

• 2-year Progression-Free Survival (PFS)

  2 years

• 2-year Distant Metastasis-Free Survival (DMFS)

  2 years

• Radiation-related adverse reactions

  During the study process and follow-up period (acute adverse reactions assessed mainly during treatment and shortly thereafter; late adverse reactions assessed during long-term follow-up according to the follow-up schedule: every 3 months within 2 years,

• Quality of Life

  Before treatment, weekly during treatment, at the end of treatment, and at each follow-up visit (follow-up visits scheduled every 3 months within 2 years, every 6 months between 2 to 5 years, and every 12 months after 5 years ).

Study Arms (2)

IMPT Group

EXPERIMENTAL

Patients in this group will receive Intensity-Modulated Proton Therapy (IMPT). The systemic therapy plan will be formulated according to clinical guidelines. These patients have histologically confirmed, previously untreated, non-metastatic (M0) nasopharyngeal carcinoma.

Radiation: Intensity-Modulated Proton Therapy (IMPT)

IMRT Group

OTHER

Patients in this group will receive Intensity-Modulated Radiotherapy (IMRT). IMRT is currently one of the most widely used techniques and serves as a standard treatment. The systemic therapy plan will be formulated according to clinical guidelines. These patients have histologically confirmed, previously untreated, non-metastatic (M0) nasopharyngeal carcinoma.

Radiation: Intensity-Modulated Radiotherapy (IMRT)

Interventions

Intensity-Modulated Proton Therapy (IMPT) RADIATION

This is the experimental arm intervention. Patients receive Intensity-Modulated Proton Therapy (IMPT) for primary nasopharyngeal carcinoma. The subjects are patients with histologically confirmed, previously untreated, non-metastatic (M0) nasopharyngeal carcinoma. Radiotherapy target volumes and doses: GTV (gross tumor volume of primary tumor and metastatic lymph nodes); CTV70Gy (GTVp + 0-5mm margin, GTVn + 0-3mm margin, reducible near organs at risk) at a dose of 69.6-70Gy; CTV50-54Gy (GTVp + 8-10mm margin + entire nasopharyngeal mucosa + adjacent high/intermediate risk structures and intermediate-risk subclinical lymph node regions) at a dose of 50-54Gy, delivered at 2Gy/(RBE) per fraction. The protocol notes that proton therapy does not use a PTV (Planning Target Volume). The systemic therapy plan is formulated according to clinical guidelines.

IMPT Group

Intensity-Modulated Radiotherapy (IMRT) RADIATION

This is the control arm intervention. Patients receive Intensity-Modulated Radiotherapy (IMRT) for primary nasopharyngeal carcinoma; IMRT is one of the current standard and widely used treatment techniques. The subjects are patients with histologically confirmed, previously untreated, non-metastatic (M0) nasopharyngeal carcinoma. Radiotherapy target volumes and doses: GTV (gross tumor volume of primary tumor and metastatic lymph nodes); CTV70Gy (GTVp + 0-5mm margin, GTVn + 0-3mm margin); PTV70 (CTV70 + 3-5mm margin, reducible near organs at risk) at a dose of 70Gy; CTV50-54Gy (GTVp + 8-10mm margin + entire nasopharyngeal mucosa + adjacent high/intermediate risk structures and intermediate-risk subclinical lymph node regions); PTV50-54 (CTV50-54 + 3-5mm margin, reducible near organs at risk) at a dose of 50-54Gy, delivered at 2Gy/(RBE) per fraction. The systemic therapy plan is formulated according to clinical guidelines.

IMRT Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent prior to the implementation of any trial-related procedures; No gender restriction, age ≥18 years and ≤75 years; Histologically confirmed, according to the latest WHO classification, including keratinizing carcinoma, non-keratinizing differentiated carcinoma, and undifferentiated carcinoma; Investigator-assessed nasopharyngeal carcinoma (cT1-4N0-3M0, AJCC 9th Edition); No prior systemic anti-tumor therapy for locally advanced disease; ECOG performance status 0-1;
• Adequate organ function, subjects must meet the following laboratory parameters:
• Absolute neutrophil count (ANC) ≥1.5x10⁹/L. Platelets ≥75×10⁹/L. Hemoglobin ≥9 g/dL (90 g/L) or ≥5.6 mmol/L; Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5×ULN (Upper Limit of Normal) Serum creatinine ≤1.5×ULN AND creatinine clearance (calculated using Cockcroft-Gault formula) ≥60 ml/min; Good coagulation function: simple laboratory abnormalities judged by the investigator to be without clinical significance; Myocardial enzyme spectrum: simple laboratory abnormalities judged by the investigator to be without clinical significance; (Note: The document lists this as criteria 8 under 3.2.1 in the main text, but the synopsis table formatting places it slightly differently though it appears to be the last point of item 7 in structure. For clarity, listing as a separate main point as per the detailed protocol structure.)

You may not qualify if:

• Presence of distant metastatic lesions (M1). Primary squamous cell carcinoma of the head and neck not originating in the nasopharynx.
• Untreated active hepatitis B (defined as HBsAg positive with HBV-DNA copy number greater than the upper limit of normal at the respective study center's laboratory); Note: Hepatitis B subjects meeting the following criteria may also be enrolled:
• HBV viral load \<1000 copies/ml (200 IU/ml) before the first dose; subjects should receive anti-HBV therapy throughout the study drug treatment period to avoid viral reactivation.
• For subjects who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring for viral reactivation is necessary.
• Active HCV infection (HCV antibody positive and HCV-RNA level above the lower limit of detection); Pregnant women;
• Presence of any severe or uncontrolled systemic diseases, for example:
• Significant and symptomatically severe, difficult-to-control abnormalities in rhythm, conduction, or morphology on resting electrocardiogram, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, or atrial fibrillation\[cite: 2\]; Unstable angina, congestive heart failure, chronic heart failure of New York Heart Association (NYHA) class ≥ 2; Any arterial thrombosis, embolism, or ischemia within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack\[cite: 2\]; History of non-infectious pneumonitis requiring glucocorticoid therapy within 1 year prior to the first dose, or currently active interstitial lung disease; Active pulmonary tuberculosis; Active or uncontrolled infection requiring systemic therapy; Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction; Liver diseases such as severe cirrhosis, decompensated liver disease, acute or chronic active hepatitis; Patients with mental disorders who cannot cooperate with treatment; History of illness or disease, treatment, or abnormal laboratory values that could interfere with study results, hinder the subject's full participation in the study, or other situations deemed unsuitable for enrollment by the investigator; or if the investigator believes there are other potential risks making the subject unsuitable for this study

Sponsors & Collaborators

• Man Hu: lead

Study Sites (1)

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

Jinan, 250117, China

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Radiotherapy, Intensity-Modulated

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

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Man Hu, Dr

  Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

  STUDY CHAIR

Central Study Contacts

Man Hu, Dr

CONTACT

86-053167626152; mhu@sdfmu.edu

Wanqi Zhu, Dr

CONTACT

86-67626624; sdszlyy@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: May 24, 2025
• First Posted: June 3, 2025
• Study Start: May 7, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2029
• Last Updated: June 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

CN (1)