Proton versus photon treatment for squamous cell cancers of the head and neck

PRORADNOR-RCT Proton Versus Photon Therapy in Head and Neck Squamous Cell Carcinomas. A Randomised, Multicentre, Phase III Clinical Trial.

PHASE3 · Oslo University Hospital · NCT07580300

This trial will test whether proton radiation or standard photon radiation leads to less long-term dry mouth, swallowing problems, pain, and speech issues in people aged 40 and older with squamous cell cancers of the oral cavity, oropharynx, hypopharynx, or larynx treated with curative radiotherapy.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment400 (estimated)
Ages40 Years to 90 Years
SexAll
SponsorOslo University Hospital (other)
Drugs / interventionschemotherapy
Locations4 sites (Bergen and 3 other locations)
Trial IDNCT07580300 on ClinicalTrials.gov

What this trial studies

This is a national, randomized phase III trial comparing proton radiotherapy to conventional photon radiotherapy for curative-intent treatment of head and neck squamous cell carcinoma. Comparative dose plans using both modalities will be created and normal tissue complication probability (NTCP) models used to identify patients predicted to benefit from protons; those with presumed benefit will be randomized 1:1 to protons or photons. The study plans to randomize 400 participants and will include patients treated definitively or postoperatively, with or without concurrent cisplatin. The primary outcome is combined toxicity burden (dry mouth, difficulty swallowing, pain, and affected speech) measured from the end of radiotherapy to 12 months after treatment.

Who should consider this trial

Good fit: Adults aged 40 or older with histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx planned for curative radiotherapy (definitive or postoperative), ECOG 0–2, able to complete questionnaires in Norwegian or English and willing to travel to Oslo or Bergen if randomized to protons are eligible.

Not a fit: Patients with small glottic cT1–T2 N0 cancers, nasopharyngeal, sinonasal, or salivary gland tumors, distant metastases, prior head and neck radiotherapy, implanted pacemakers/defibrillators, or a recent other malignancy are excluded and unlikely to be helped by this trial.

Why it matters

Potential benefit: If successful, proton therapy could substantially reduce combined radiation-related toxicities and improve quality of life compared with standard photon therapy.

How similar studies have performed: Smaller dosimetric comparisons and observational studies have suggested toxicity advantages for protons, but large randomized phase III evidence is limited, making this trial an important test of clinical benefit.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Signed informed consent.
2. Age ≥ 40 years.
3. Histological or cytological verified squamous cell carcinoma of the following head and neck regions; oral cavity, oropharynx, hypopharynx or larynx.
4. Planned for standard radiotherapy with curative intent, either as definitive or postoperative treatment with or without concomitant chemotherapy (cisplatin).
5. ECOG performance status 0-2.
6. Ability to fill in patient questionnaires and comply with study procedures.
7. Able to answer questionnaires in Norwegian or English.
8. Willing to travel to Oslo or Bergen for proton therapy if randomised to experimental arm.

Exclusion Criteria:

1. Glottic cancers, cT1-T2 cN0 cM0.
2. Nasopharyngeal carcinomas, sino-nasal cancers, and head and neck salivary gland carcinomas.
3. Distant metastasis.
4. Previous radiotherapy to the head and neck.
5. Patients with pacemakers and/or implanted defibrillators.
6. Prior malignancy within the last 5 years. Not including radically resected non-melanoma skin cancer or low-risk early-stage prostate cancer.
7. Not able to participate due to equipment restrictions (weight limit treatment board 150 kg).
8. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could, at the investigator's opinion, interfere with the participant's safety or study participation.

Where this trial is running

Bergen and 3 other locations

Study contacts

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.

View on ClinicalTrials.gov →

Conditions: HNSCC, Proton

Last reviewed 2026-05-15 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.