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A Pharmacokinetic/Pharmacodynamic Study of the Glucocorticoid Receptor Antagonist Mifepristone Combined with Enzalutamide in Castrate Resistant Prostate Cancer

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Technical Report,01 Dec 2014,30 Nov 2015

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University of Chicago Chicago United States

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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 III 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 second year of this award, the trial accrued to the phase I portion. The phase I study has completed the third dosing cohort. Thus far the combination of mifepristone and enzalutamide has been well tolerated with no dose limiting toxicities. Based on safety and pharmacokinetics it is anticipated this will be the recommended phase II dose, and that the phase II will start Q2 2016. Site selection for phase II underway.

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