RAdiotherapy With FDG-PET Guided Dose-PAINTing Compared With Standard Radiotherapy for Primary Head and Neck Cancer-3 Randomized, Multicentre, Phase II Trial
Trial ID: NCT06297902
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: NA
Start date: 2024-08-19
Completion date: 2030-06
Sponsor: Oslo University Hospital
Conditions: Head and Neck Cancer; Radiotherapy Side Effect
Interventions: Dose painting
Locations: Haukeland University Hospital; Oslo University Hospital; St. Olavs Hospital
Countries: Norway; Norway; Norway
Enrollment: 100
Age range: 18 Years - None
Sex: ALL

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.

Eligibility criteria:
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

Outcomes:
Late mucosal ulcer