A phase 1 trial of the oral DNA methyltransferase inhibitor CC-486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors.

ABSTRACT:

Background

Epigenetic abnormalities are manifold in all solid tumors and include changes in chromatin configuration and DNA methylation. The authors designed a phase 1 study to evaluate the oral DNA methyltransferase inhibitor CC-486 combined with the histone deacetylase inhibitor romidepsin in advanced solid tumors with dose expansion to further evaluate pharmacodynamics and possible clinical benefit of the recommended phase 2 dose (RP2D).

Methods

This was a phase 1 study with a 3 + 3 dose-escalation design and an expansion phase for patients with virally mediated cancers. The disease control rate (DCR) was the primary outcome for the expansion cohort. Correlative studies included long interspersed nucleotide element 1 (LINE-1) methylation and drug exposure in blood samples

SUBMITTER: Gaillard SL 

PROVIDER: S-EPMC6663621 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature