Radioprotective effects of parthenolide lotion against skin injury caused by radiation (REPAIR-1): protocol for a phase 0, non-randomised, double-blind, interventional pilot study

IntroductionRadiation forms the basis of many successful anti-cancer treatment regimens, killing tumour cells by irreversibly damaging their DNA. Unfortunately, radiation indiscriminately kills healthy cells, causing a range of debilitating and highly impactful side effects. One of the most common side effects is damage and burning of the skin, termed radiation-induced dermatitis (RID), which occurs in up to 95% of people undergoing radiation therapy. Although common, RID cannot be prevented and is inadequately managed with various topical solutions. Parthenolide has emerged as a promising radioprotective agent for the management of RID. The REPAIR-1 study is a phase 0, prospective, non-randomised, double-blind, interventional pilot study which aims to assess the efficacy of topical parthenolide application in limiting severe RID. Methods and analysisThe REPAIR-1 study will be conducted at the Royal Adelaide Hospital, South Australia, Australia. Eligible participants for the REPAIR-1 study include adults diagnosed with locally advanced cancer of the head/neck scheduled to receive definitive, bilateral radiation therapy. Once enrolled, eligible participants will receive application of a 1% parthenolide, or placebo lotion, to opposite sides of the head/neck region before and after daily radiation therapy for the duration of their treatment course (6-7 weeks). The primary outcome of this study is absolute RID severity after 4 weeks of radiation therapy defined by both CTCAE v5.0 criteria and the RISRAS tool. Ethics and disseminationThis protocol has been approved by Central Adelaide Local Health Network Human Research Ethics Committee (2024/HRE00241). All participants will be required to provide written informed consent. Results will be disseminated in peer-reviewed journals, and at scientific conferences. Trial registration numberACTRN12625000456459