Phase I trial of DNA methyltransferase inhibitor guadecitabine combined with cisplatin and gemcitabine for solid malignancies including urothelial carcinoma (SPIRE).

Pre-clinical data indicate that DNA methyltransferase inhibition will circumvent cisplatin resistance in various cancers.

SPIRE comprised a dose escalation phase for incurable metastatic solid cancers, followed by a randomised dose expansion phase for neoadjuvant treatment of T2-4a N0 M0 bladder urothelial carcinoma.