Proton Versus Photon Therapy in Head and Neck Squamous Cell Carcinomas. (PRORADNOR-RCT)

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

A national, randomized, clinical trial (phase III) investigating radiotherapy with protons compared with photons for patients with squamous cell carcinoma of the head and neck area eligible for radiotherapy, either radical or postoperative, with curative intent. Comparative dose plans with protons and photons will be prepared, and the probability of toxicity evaluated with NTCP models. Patients with presumed benefit from protons will be randomized 1:1 to treatment with protons or photons. The number of randomized participants will be 400. The primary endpoint is "combined toxicity burden" - dry mouth, difficulty swallowing, pain and affected speech in the period after the end of radiotherapy to 12 months after treatment.

Study Overview

• Status: Recruiting
• Conditions: HNSCC
• Intervention / Treatment: Radiation: Proton Radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Barbro Berggren, Cand.Scient; Phone Number: 004722934000; Email: barbbe@ous-hf.no

Study Locations

• Norway
  • Bergen, Norway, 5051
    • Not yet recruiting
    • Haukeland University Hospital
    • Contact: Jon Espen Dale, MD PhD; Phone Number: 004755975000; Email: jon.espen.dale@helse-bergen.no
    • Principal Investigator: Jon Espen Dale, MD PhD
  • Oslo, Norway, 0379
    • Recruiting
    • Oslo University Hospital, Radiumhospitalet
    • Contact: Hanne Eide, MD PhD; Phone Number: 004722934000; Email: haeid@ous-hf.no
    • Principal Investigator: Hanne Eide, MD PhD
  • Tromsø, Norway, 9038
    • Not yet recruiting
    • University Hospital of Northern Norway
    • Contact: Thomas K. Kilvær, MD Associate prof.; Phone Number: 004777626000; Email: Thomas.Kilvaer@unn.no
    • Principal Investigator: Thomas Kilvær, MD Associate prof.
  • Trondheim, Norway, 7006
    • Not yet recruiting
    • St. Olavs Hospital
    • Contact: Mirjam Alsaker, MD PhD; Phone Number: 004772573000; Email: Mirjam.Delange.Alsaker@stolav.no
    • Principal Investigator: Mirjam Alsaker, MD PhD

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proton, Radiotherapy	Radiation: Proton Radiotherapy; Proton versus Photon
Active Comparator: Photon, Radiotherapy	Radiation: Proton Radiotherapy; Proton versus Photon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The combined burden of patient-reported dysphagia, xerostomia, pain and speech measured as the area under the curve (AUC) with EORTC QLQ-H&N43 at baseline, end of treatment, 3-, 6- and 12-months following radiotherapy.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from date of randomisation to date of loco-regional failure, distant metastasis or death from all causes, whichever comes first.		10 Years
Occurrence of at least one event grade 2 toxicity as defined by CTCAE v5.0 at 12 months.Occurrence of at least one event grade 3 toxicity as defined by CTCAE v5.0 at 12 months.Occurrence of at least one event grade 4 toxicity as defined by CTCAE v5.0.		12 Months
Time from date of randomisation to date of death (all causes).		10 Years
Time from date of randomisation to the first documented loco-regional failure.		3 Years
The combined toxicity burden of dysphagia, xerostomia, pain and speech measured with QLQ-H&N43 5 years after treatment.	Toxicity burden measured with QLQ-H&N43	5 Years

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: South-Eastern Norway Regional Health Authority; Klinbeforsk
• Investigators: Principal Investigator: Hanne Eide, MD PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2026
• Primary Completion (Estimated): April 28, 2030
• Study Completion (Estimated): April 28, 2055

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HNSCC; Proton
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: 912158

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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