VB-NEO

• Research type

  Research Study

• Full title

  A pharmacodynamic study of the effects of neo-adjuvant sodium valporate and bortezomib in patients with melanoma or colorectal cancer.

• IRAS ID

  5503

• Eudract number

  2008-003013-27

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  More effective therapy is needed for melanoma and colorectal cancer. Trials of adjuvant therapy require large numbers of patients and many years to show whether an intervention is effective. Studies of promising agents given prior to planned surgery allow a more rapid assessment as they offer the potential to evaluate markers of efficacy and direct the development of drug combinations.Melanoma and colorectal cancer cell lines undergo cell death after treatment of Histone deacetylase (HDAC) inhibitors, and these drugs have shown synergy with ionising radiation and a variety of cancer treatments. Clinical activity has been seen as a single agent, and in combination with epirubicin. Sodium valproate inhibits tumour growth in vivo in pre-clinical models and synergises with a number of anti-cancer agents. Phase 1 studies show the drug to be well-tolerated at doses that produce these effects. Bortezomib is a proteosome inhibitor which are known to sensitize tumor cells to widely used cancer drugs, including ionizing radiation, and DNA cross-linking agents. Bortezomib has limited single agent activity in solid tumours, but synergises with HDAC inhibitors in terms of tumour cell killing.The aims of this study, besides defining the effects of sodium valproate in melanoma, are to identify the impact of HDAC inhibition with respect to the apoptotic machinery and aspects of DNA repair, and investigate the potential for synergy with proteosome inhibitors. These observations will guide pre-clinical experiments and, where identified, clinical evaluation of promising combinations.

• REC name

  South Central - Oxford C Research Ethics Committee

• REC reference

  08/H0606/111

• Date of REC Opinion

  9 Jan 2009

• REC opinion

  Further Information Favourable Opinion