A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas.

ABSTRACT:

Purpose

Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-κB and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity.

Experimental design

Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2-related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the dru

SUBMITTER: Hong DS 

PROVIDER: S-EPMC4494099 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature