A Pharmacokinetic/Pharmacodynamic Study of the Glucocorticoid Receptor Antagonist Mifepristone Combined with Enzalutamide in Castrate-Resistant Prostate Cancer
Abstract
This is a Clinical Exploration Award funding a clinical trial for patients with metastatic, castration resistant prostate cancer (CRPC). For patients with metastatic CRPC, there are few established therapeutic options and the prognosis remains dire. The overarching goal of this award is to build on concept that under the selective pressure of androgen receptor (AR) targeted therapies, prostate cancer adapts. One way it adapts is by upregulating another hormone receptor, the glucocorticoid receptor (GR), which may compensate for diminished AR activity. The clinical trial within this award is a phase I/II clinical trial of the GR antagonist mifepristone in combination with the FDA-approved AR antagonist enzalutamide. The first objective is, within the context of a phase I clinical trial, to establish safe and pharmacologically active doses of the two drugs for use in combination for daily dosing. The second objective is to use pharmacodynamic biomarkers to support the hypothesis that GR antagonism in combination with AR antagonism will delay CRPC progression. During the first year of this award, the trial has successfully opened at the lead site, which is a culmination of FDA IND acceptance as well as scientific and IRB approval. The phase I study is in the second dosing cohort. Thus far the combination of mifepristone and enzalutamide has been well tolerated with no dose limiting toxicities. The current cohort has dose-escalated the enzalutamide and it is anticipated, based on safety and pharmacokinetics that this will be the recommended phase II dose, and that the phase II will start this year.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2014
- Accession Number
- ADA613184
Entities
People
- Russell Szmulewitz
Organizations
- University of Chicago