protocolSection identificationModule nctId: NCT06297902, orgStudyIdInfo id: 2023_31, briefTitle: RAdiotherapy With FDG-PET Guided Dose-PAINTing Compared With Standard Radiotherapy for Primary Head and Neck Cancer-3, acronym: RADPAINT-3, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-05, primaryCompletionDateStruct date: 2027-06, completionDateStruct date: 2030-06, studyFirstPostDateStruct date: 2024-03-07, lastUpdatePostDateStruct date: 2024-03-07, sponsorCollaboratorsModule leadSponsor name: Oslo University Hospital, class: OTHER, collaborators name: Haukeland University Hospital, collaborators name: St. Olavs Hospital, collaborators name: Norwegian University of Life Sciences, descriptionModule briefSummary: 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., conditionsModule conditions: Head and Neck Cancer, conditions: Radiotherapy Side Effect, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 100, type: ESTIMATED, armsInterventionsModule interventions name: Dose painting, outcomesModule primaryOutcomes measure: Late mucosal ulcer, secondaryOutcomes measure: Early toxicity, secondaryOutcomes measure: Late toxicity, secondaryOutcomes measure: Odynophagia, secondaryOutcomes measure: Health-related quality of life, otherOutcomes measure: Cytokines, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule, hasResults: False