RAdiotherapy With FDG-PET Guided Dose-PAINTing Compared With Standard Radiotherapy for Primary Head and Neck Cancer-3 (RADPAINT-3)

RAdiotherapy With FDG-PET Guided Dose-PAINTing Compared With Standard Radiotherapy for Primary Head and Neck Cancer-3 Randomized, Multicentre, Phase II Trial

The objective of the RADPAINT-3 trial is to investigate whether dose painting is safe compared to standard radiotherapy. RADPAINT-3 is a randomized, non-inferiority, multi-center phase II study, initiated at the Section for Head and Neck Cancer, Department of Oncology, Oslo University Hospital, accruing from first half of 2024. The primary endpoint is frequency of grade ≥ 3 (CTCAE v5.0) mucosal ulcers one year after treatment. The expected inclusion period is three years, total study duration is six years and planned inclusion number is 100 patients. The collaborating sites are St Olav´s Hospital and Haukeland University Hospital. The patients will be randomized 1:1 to either standard radiotherapy (2 Gy x 34; total dose 68 Gy) or experimental radiotherapy (dose painting). All patients will have 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose positron emission computed tomography (FDG-PET/CT) prior to radiotherapy. In the experimental arm, we will escalate the dose to the hypermetabolic part of the tumor (maximum point dose 83.3 Gy), shown in pre-treatment FDG-PET images. Dose escalation will be applied to these regions during the first half of the fractionated treatment (17 of 34 fractions). The patients in both arms will receive concomitant nimorazole (hypoxic radiosensitizer) and concomitant cisplatin if indicated according to standard treatment. The main inclusion criterion is patients with human-papillomavirus (HPV)-unrelated head and neck cancer with poor prognosis.

The RADPAINT-3 trial includes a translational sub-study where we aim to elucidate underlying mechanisms related to the radiotherapy effect, by investigating blood samples. Analysis of cytokines in repetitive blood samples may predict both tumor response and toxicity. The data derived from this sub-study, will be further explored using artificial intelligence.

If RADPAINT-3 shows that there is no excess toxicity, we will continue the study after a new protocol has been approved. The new primary endpoint will be local control at 1 year after radiotherapy. Power analysis show that we will need in total 182 evaluable patients including the 100 patients from RADPAINT-3. The translational sub-study will then be extended to investigate genetic expression data from pre-therapy routine tumor biopsies and correlate this with the analysis of blood samples and tumor control.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Radiotherapy Side Effect
• Intervention / Treatment: Radiation: Dose painting

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Einar Dale, PhD; Phone Number: +4722934000; Email: eindal@ous-hf.no

Study Locations

• Norway
  • Bergen, Norway, N-5021
    • Recruiting
    • Haukeland University Hospital
    • Contact: Marianne Brydøy, PhD
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Einar Dale, PhD; Phone Number: +4722934000; Email: eindal@ous-hf.no
  • Trondheim, Norway, N-7006
    • Not yet recruiting
    • St. Olavs Hospital
    • Contact: Mirjam D Alsaker, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically or cytologically verified invasive squamous cell carcinoma of the head and neck region; Sinonasal cancer, oral cavity cancer, hypopharynx cancer, larynx cancer, HPV negative oropharyngeal cancer and T4 (any N) HPV positive oropharyngeal cancer.
2. Patients planned for standard curative RT (with or without concomitant chemotherapy [cisplatin, or cetuximab], with or without nimorazole hypoxic cell radiosensitizer)
3. Age > 18 years
4. WHO performance status 0-2
5. Signed informed consent
6. Ability to understand information about the study and to complete questionnaires

Exclusion Criteria:

1. All diagnoses, cT1 cN0-N1 cM0
2. Glottic cancer cT1-T2 cN0 cM0
3. HPV positive oropharyngeal carcinoma T1-T3 (any N)
4. Diabetes mellitus
5. Use of anticoagulant medication
6. Active smoking and/or alcohol abuse

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: Dose painting; Radiation dose will be escalated to the hypermetabolic part of the tumor (maximum point dose 83.3 Gy), shown in pre-treatment FDG-PET images. Dose escalation will be applied to these regions during the first half of the fractionated treatment (17 of 34 fractions).	Radiation: Dose painting; Dose painting
No Intervention: Standard radiotherapy; Homogeneous dose to the tumor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late mucosal ulcer	Presence of grade ≥ 3 mucosal ulcers (as defined by CTCAE v5.0)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early toxicity	CTCAE v5.0	At end of treatment - 7 weeks after inclusion
Late toxicity	CTCAE v5.0	1 and 3 years
Odynophagia	EORTC QLQ-H&N43	1 year
Health-related quality of life	EORTC QLQ-C30	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokines	Identify panels of cytokines measured in blood at the start of RT to predict the risk of toxicity. Blood samples will be collected before the start of treatment, after 10 Gy of radiation, at the end of therapy (7 weeks after inclusion), after 3 months of follow up (coinciding with response evaluation with FDG-PET/CT), after 1 year and fresh frozen at -80°C. Cytokine profiling will be performed by the 48-plex Luminex assay,	1 year and 3 years

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Haukeland University Hospital; St. Olavs Hospital; Norwegian University of Life Sciences
• Investigators: Principal Investigator: Einar Dale, Oslo University Hospital

Publications and helpful links

General Publications

• Evensen ME, Furre T, Malinen E, Londalen AM, Dale E. Mucosa-sparing dose painting of head and neck cancer. Acta Oncol. 2022 Feb;61(2):141-145. doi: 10.1080/0284186X.2021.2022200. Epub 2022 Jan 6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Radiotherapy; Positron emission tomography; Dose painting; 18F-FDG
• Additional Relevant MeSH Terms: Wounds and Injuries; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Radiation Injuries
• Other Study ID Numbers: 2023_31

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