|Funding||Secretary of state for health|
Individuals can develop patches (oral dysplasia) on the lining of the mouth which are at risk of developing into cancer.
Standard treatments include Surgery or close surveillance, although these treatments are not completely effective, as
up to 25% of patients progress to oral cancer even after Surgery. Oral cancer treatments can be curative, especially
when caught early, but the side effects include damage to speech, swallowing, appearance and reduction in quality of
life, which are permanent. Additionally treatment for oral cancer carries a high economic burden and the World Health
Organisation has recommended a shift in policy towards early diagnosis and prevention. Survival rates for oral cancer
have remained largely unchanged for decades, at around 50-55% overall survival by 5 years. There is, therefore, a
need to develop and evaluate new prevention treatments for this condition. It is thought that more effective treatment for
oral dysplasia would reduce the incidence of oral cancer.
SAVER is a phase II clinical trial with embedded mechanistic and feasibility studies. It is randomized, double blind and
placebo controlled with a planned recruitment of 110 patients. The randomisation is in the ratio 2 SV (73 patients) :1
placebo (37 patients). The study population includes patients with premalignant oral lesions that have a histological
diagnosis of oral epithelial dysplasia (OED) and are at high risk (considered to be at least 20% over 5 years of
The aim of this phase II trial is to investigate the effects of sodium valproate as epigenetic chemopreventive therapy on
high risk oral dysplasia. In particular, we will establish: clinical activity, mechanismof action and, feasibility of
conducting such research in the NHS, in order to inform a decision on a larger phase III trial.
The primary endpoint is a measure of clinical activity and a surrogate – it is a composite of clinical, pathology and
molecular lesional changes which has been previously used, with peer review, in randomised trials, within the same
field(20). It is derived from clinical measurement, photographs and punch biopsy tissue comparing baseline to
primary endpoint (4 months). Approximately 10 research sites are to be opened to recruitment in the UK and Ireland.