Proton Therapy for Recurrent Nasopharyngeal Carcinoma

A Prospective Phase II Clinical Study of Proton Therapy for Recurrent Nasopharyngeal Carcinoma

The above studies show that most of the supportive evidence for the reduction of toxicity and improvement of efficacy of proton therapy for recurrent Nasopharyngeal carcinoma(NPC) comes from various observational and retrospective studies, lacking high-level evidence-based medical evidence. The conduct of this study will explore the safety and efficacy of intensity-modulated proton radiotherapy for recurrent NPC and provide more high-quality evidence-based medical evidence for proton therapy of recurrent cancer.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Nasopharyngeal Carcinoma
• Intervention / Treatment: Device: Proton radiation therapy; Radiation: Proton therapy

Detailed Description

Radiotherapy is the main treatment for nasopharyngeal carcinoma (NPC). Currently, the 5-year local control rate for NPC is 80% to 85% . However, some patients inevitably experience local recurrence. For early recurrent tumors, salvage surgery can achieve satisfactory tumor control and improve the quality of life for patients, thus being a reasonable treatment option. However, many recurrent tumors are too advanced to be resected. For these unresectable tumors, high-dose re-irradiation is the only potentially curative method. Intensity-modulated radiotherapy (IMRT), as the main treatment for NPC, has achieved encouraging results in local control, survival, and tolerable toxicity. However, there are still two problems with the treatment plan of IMRT for unresectable recurrent NPC: first, the survival of patients is still poor. It has been reported that the 2-year local progression-free survival rate of locally recurrent NPC patients treated with IMRT combined with chemotherapy is approximately 56% to 76.9%, and the 2-year overall survival rate is only 44% to 68%. Second, severe adverse reactions caused by re-irradiation are the most important cause of treatment failure. About 64.9% of patients experience grade 3 to 5 late radiation-related toxicities such as mucosal necrosis and temporal lobe necrosis . Therefore, in recent years, researchers have been trying more advanced radiotherapy techniques to improve the efficacy of patients with unresectable locally recurrent NPC and reduce radiotherapy-related complications.

Proton radiotherapy is currently recognized as the cutting-edge radiotherapy technology internationally, mainly through particle beam irradiation of tumors. Particles enter with low energy and gradually increase energy deposition until a rapid increase occurs within the "Bragg peak", that is, the energy is elevated and released entirely when reaching the tumor site, achieving a "directed explosion" on the tumor, and then rapidly decreases after passing through the tumor site, decaying to 0 within a very short distance, resulting in minimal radiation to the surrounding normal tissues and reducing the occurrence of long-term adverse reactions. Therefore, proton radiotherapy is an ideal and preferred choice for recurrent NPC. However, there are currently few studies on proton and heavy ion therapy for recurrent NPC, and most are retrospective and observational studies. Although some studies have included patients with unresectable locally recurrent NPC who received re-irradiation with protons, they have not provided detailed information on the specific outcomes of these patients . On the other hand, Linda et al.'s historical study reported that the 2-year overall survival (OS) and local progression-free survival rates of 16 patients with recurrent NPC who received proton beam re-irradiation (median dose of 60.1 Gy relative biological effectiveness (RBE)) were both 50%, and it caused minimal side effects on the central nervous system. Meanwhile, Dionisi et al. reported that 17 patients (12 of whom were rT4 patients) received proton re-irradiation, with a median follow-up of 10 months: 23.5% of the patients experienced grade ≥ 3 late toxicities; the 18-month OS and local control rates were 54.4% and 66.6%, respectively.

The above studies show that most of the supportive evidence for the reduction of toxicity and improvement of efficacy of proton therapy for recurrent NPC comes from various observational and retrospective studies, lacking high-level evidence-based medical evidence. The conduct of this study will explore the safety and efficacy of intensity-modulated proton radiotherapy for recurrent NPC and provide more high-quality evidence-based medical evidence for proton therapy of recurrent cancer.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Taize Yuan, M.D., Ph.D.; Phone Number: 8620-32506195; Email: taize.yuan@ccm.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangzhou Concord Cancer Center
      • Contact: Yuan taize, Doctor; Email: taize.yuan@ccm.cn
  • Guangzhou
    • Guanzhou, Guangzhou, China
      • Recruiting
      • Guangzhou Concord Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Non-metastatic squamous cell carcinoma of the nasopharynx with biopsy confirmation, at stage ≥ T2b and/or with positive lymph nodes, (2) Pathological type WHO I-III

2. PS score (according to Eastern Cooperative Oncology Group (ECOG) standard) 0-1.

   Age ≥ 18 years.

3. Expected survival period ≥ 6 months
4. Before treatment, evaluate the tumor range and size of the patient.
5. Nutritional and general physical condition must be able to tolerate the recommended radiotherapy and chemotherapy.

Exclusion Criteria:

1. Evidence of distant metastasis in stage IVc
2. Patients with isolated recurrence of cervical lymph nodes;
3. Patients have participated in other interventional trials for tumors
4. Having suffered from other malignant tumors within 5 years (excluding melanoma skin cancer) or tumors originating from the head and neck region Untreated active infections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Proton therapy group; All patients received proton therapy, with a prescribed dose of 60-66 Gy in 30-33 fractions, 5 days per week, for a total of 6-6.5 weeks.

Device: Proton radiation therapy; Radiation: Proton Therapy System (ProBeam); Radiation: Proton therapy; Treatment planning and target delineation: All patients were in the supine position with the head extended backward, with the mask fixed, and enhanced computed tomography (CT) scans were performed for positioning. The slice thickness was 1.25mm. The gross tumor volume (GTV) included the recurrent primary lesion. The clinical target volume (CTV) included the anatomical expansion of the tumor and the suspicious lesions visible under the microscope. The CTV was defined as an expansion of 5-10mm outside the GTV. Radiation dose and treatment plan: The prescribed dose was 60-66 Gray (Gy) delivered in 30-33 fractions. Plan design and dose verification: The physicist designed radiotherapy plans according to the requirements of the physician. After the radiotherapy plan was designed, it was evaluated and repeatedly optimized by the physician and the physicist until satisfactory results were achieved. Treatment: was required for each treatment session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe late complications	The proportion of subjects whose toxicity reaction is level 3 during the clinical trial period. The researchers record AE that appeared during the clinical trial cycle and grade it according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From enrollment to the three-year follow-up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival time	It is defined as the time interval from enrollment to the point of death due to any cause. If there is no death, it is calculated as the time of the last follow-up.	From enrollment to the three-year follow-up period
Local progression-free survival time	It is defined as the time interval from the start of the study to the occurrence of tumor progression or death due to any cause. If there is no tumor progression, it is calculated up to the last follow-up time.	From enrollment to the three-year follow-up period
Short-term treatment responses	The proportion of patients who achieved treatment response at the end of neoadjuvant chemotherapy and 3 months after the radiotherapy to evaluate the short-term therapeutic effect. Treatment response will be assessed according to the The Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD).	From enrollment to the three-month follow-up period

Collaborators and Investigators

• Sponsor: Guangzhou Concord Cancer Center
• Investigators: Study Director: Yuan Taize, private hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Estimated): March 10, 2028
• Study Completion (Estimated): March 10, 2028

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: proton therapy; recurrent nasopharyngeal carcinoma
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Therapeutics; Radiotherapy; Heavy Ion Radiotherapy; Proton Therapy
• Other Study ID Numbers: 2024-IIT-007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No