VADER: A phase II randomised controlled trial to determine the efficacy of combining the HDAC inhibitor sodium valproate with EGFR monoclonal antibody (panitumumab or cetuximab) maintenance in the first-line treatment of patients with RAS wild type metastatic CRC

Extensive pre-clinical studies have shown that histone deacetylase (HDAC) inhibitors have synergistic anti-tumour effects in combination with epidermal growth factor receptor (EGFR) inhibitors in CRC cell lines including the induction of cell cycle arrest, differentiation and apoptosis. These effects are associated with additive suppression of the MYC oncogene and alteration of pro- and anti-apoptotic gene expression in favour of apoptosis.

VADER will test the efficacy of this combination by repurposing sodium valproate (VPA). VPA is best known as an anti-epileptic agent but also has effects as an HDAC inhibitor.  Given its well-defined safety profile and long history of use, we will test whether it can be re-purposed to exploit its HDAC inhibitory activity to improve outcomes for patients with mCRC.