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

Not Applicable

Recruiting

• Conditions: Radiotherapy Side Effect; Head and Neck Cancer
• Interventions: Radiation: Dose painting

• Registration Number: NCT06297902
• Lead Sponsor: Oslo University Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-02-12
• Study First Submitted QC: 2024-02-29
• Study First Posted: 2024-03-07
• Study Start: 2024-08-19
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-19
• Last Update Posted: 2025-02-21
• Primary Completion: 2027-06
• Study Completion: 2030-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose painting	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).

Primary Outcome Measures

Name	Time	Method
Late mucosal ulcer	1 year	Presence of grade ≥ 3 mucosal ulcers (as defined by CTCAE v5.0)

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Haukeland University Hospital; 🇳🇴 Bergen, Norway

St. Olavs Hospital; 🇳🇴 Trondheim, Norway

Oslo University Hospital; 🇳🇴 Oslo, Norway