Proton versus photon radiation for advanced nasopharyngeal cancer

A Prospective, Randomized, Open-Label, Multicenter Phase III Clinical Study Comparing Intensity-Modulated Proton Therapy and Intensity-Modulated Photon Radiotherapy in Locally Advanced Nasopharyngeal Carcinoma

Phase 3 Interventional Shandong Cancer Hospital and Institute · NCT07340515

This trial will test whether proton radiation (IMPT) or standard photon IMRT causes fewer severe side effects and improves 3-year progression-free survival for adults with newly diagnosed, high-risk locally advanced nasopharyngeal cancer who receive induction chemotherapy followed by concurrent chemoradiotherapy with immunotherapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment300 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorShandong Cancer Hospital and Institute Academic / other
Drugs / interventionschemotherapy, immunotherapy
Locations1 site (Jinan, Shandong)
Trial IDNCT07340515 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, randomized Phase III trial enrolling adults with newly diagnosed, high‑risk locoregionally advanced nasopharyngeal carcinoma (WHO type II/III, clinical T4 or N3, M0). All participants receive three cycles of induction chemotherapy with gemcitabine plus cisplatin, then concurrent chemoradiotherapy combined with immunotherapy, during which they are randomized 1:1 to receive either intensity-modulated proton therapy (IMPT) or intensity-modulated photon radiotherapy (IMRT). The co-primary endpoints are the incidence of grade ≥3 acute treatment-related toxicities and 3-year progression-free survival, with secondary endpoints including overall survival, locoregional relapse-free survival, distant metastasis-free survival, objective response rate, late toxicities, and quality of life. Toxicities are graded by CTCAE v5.0 (with specific ototoxicity measures), and radiotherapy is delivered per protocol-defined target delineation, dose, and fractionation schedules.

Who should consider this trial

Good fit: Adults aged 18–70 with histologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO II/III) staged T4 or N3 M0, ECOG 0–1, no prior anti-tumor therapy, and who can receive induction gemcitabine/cisplatin followed by concurrent chemoradiotherapy with immunotherapy are ideal candidates.

Not a fit: Patients with distant metastases, prior radiotherapy or systemic therapy for nasopharyngeal carcinoma, active autoimmune disease requiring systemic treatment, poor performance status, or those unable to attend the participating centers are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, proton therapy could reduce severe acute radiation-related side effects and better preserve hearing and other normal-tissue function while maintaining or improving disease control.

How similar studies have performed: Dosimetric analyses and retrospective clinical series suggest proton therapy can lower dose to normal tissues and may reduce some toxicities, but randomized Phase III evidence in nasopharyngeal carcinoma is currently limited.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Age 18 to 70 years
* Histologically confirmed nasopharyngeal carcinoma (WHO type II or III)
* High-risk locoregionally advanced disease defined as clinical stage T4 or N3, M0, according to the AJCC staging system
* No prior anti-tumor therapy for nasopharyngeal carcinoma, including radiotherapy, chemotherapy, targeted therapy, or immunotherapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Adequate organ function as defined in the study protocol
* Eligible to receive induction chemotherapy followed by concurrent chemoradiotherapy combined with immunotherapy as specified in the protocol
* Ability to understand and willingness to sign written informed consent

Exclusion Criteria:

* Evidence of distant metastasis (M1 disease)
* Prior radiotherapy, chemotherapy, targeted therapy, or immunotherapy for nasopharyngeal carcinoma
* Active autoimmune disease requiring systemic therapy
* Uncontrolled infection or severe comorbidities that may affect treatment tolerance
* Pregnancy or breastfeeding
* Known allergy, hypersensitivity, or contraindication to study medications as defined in the protocol
* Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation

Where this trial is running

Jinan, Shandong

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Nasopharyngeal CarcinomaProton TherapyIMPTIntensity-Modulated Proton TherapyChemoradiotherapy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.