Head and Neck Fibrosis clinical trials

PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients

Objectives: This is a feasibility study in preparation for the main multicentre randomised trial, which is anticipated to have two arms: - Arm A: the current best standard of care [rehabilitation exercises] - Arm B: the current best standard of care [rehabilitation exercises] + the experimental intervention In this feasibility trial the following aspects will be evaluated: - Recruitment rates [that is also willingness to be randomised] - Feasibility of providing the experimental intervention at the NHS study sites - Retention rate/drop out rate - Feasibility and acceptability of (i) proposed primary outcome [patient-centred], (ii) a range of additional patient-centred and clinician-centred outcomes - Standard deviation of the proposed primary outcome so to inform sample size calculation of the main trial. - Safety/toxicity of the study medication. Type of trial: Multicentre, parallel group, randomised controlled trial in 50 patients with radiotherapy-induced fibrosis of the head and neck. Trial design and methods: Participants over the age of 18, with radiotherapy-induced fibrosis of the head and neck will be given information about the trial and invited to participate. 50 participants who consent will be recruited and randomised to either: - Treatment with pentoxifylline 400 mg tablets twice a day [total 800mg/day] + 500IU tocopherol acetate solution twice a day [total 1000 IU/day] in addition to best standard care [a structured programme of rehabilitation exercises] for 6 months or - Best standard of care [a structured programme of rehabilitation exercises] for 6 months. Randomisation will be carried out online Trial duration per subject: 6 months Estimated total trial duration: 56 months Planned trial sites: Multi-site Total number of subjects planned: 50 participants Main inclusion/exclusion criteria: Inclusion Criteria: - Subjects aged ≥18 years - Previous history of Head & Neck Cancer - Previous radiotherapy to the Head & Neck - minimum 50 Gy completed at least 12 months before screening visit - Cancer-free for a minimum of 12 months after completion of radiotherapy. - Diagnosis of radiotherapy-induced fibrosis of the head and neck: trismus and/or dysphagia Exclusion Criteria: - History of primary cancer resection and/or reconstructive surgery to anatomical areas involved in swallowing and/or chewing. - Concomitant presence of other disorders that may cause pharyngeal/oral fibrosis - Known hypersensitivity to pentoxifylline or tocopherol (vitamin E). - History of acute porphyrias or haemorrhagic disorders - Active/ongoing hypotension - Diabetes - Pregnancy - Subjects with osteoradionecrosis - Breastfeeding mothers - Subjects with a MIO <12mm Statistical methodology and analysis: Analysis of this feasibility trial will be mainly descriptive, measuring recruitment rate, acceptance of randomisation, attrition from treatment and trial, and completion rates for the outcome measures (to gauge acceptability and appropriateness).