The direct detection of high-energy cosmic rays up to the PeV region is one of the major challenges for the next generation of space-borne cosmic-ray detectors. The physics performance will be primarily determined by their geometrical acceptance and energy resolution. CaloCube is a homogeneous calorimeter whose geometry allows an almost isotropic response, so as to detect particles arriving from every direction in space, thus maximizing the acceptance. A comparative study of different scintillating materials and mechanical structures has been performed by means of Monte Carlo simulation. The scintillation-Cherenkov dual read-out technique has been also considered and its benefit evaluated.