In stage 1 of the study, the maximum tolerated dose (MTD) will be determined from an initial cohort of 16 patients. In the second stage, 8 further patients will be added to allow a minimum effective dose (MED) to be determined from all patients. Patients will be block randomised in a two-period crossover design to the order in which they receive both TR004 and placebo. In each successive pair of subjects, one will first receive TR004 and the other will first receive placebo at the same dose as each other and in each period.