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Clin Cancer Res. 2016 Mar 15;22(6):1356-63. doi: 10.1158/1078-0432.CCR-15-1432. Epub 2015 Nov 2.

Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer.

Author information

1
University of Washington, Seattle, Washington.
2
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, James Buchanan Brady Urological Institute, Baltimore, Maryland.
3
UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.
4
San Bernadino Urological Associates, San Bernadino, California.
5
Indiana University School of Medicine, Indianapolis, Indiana.
6
Institute for Translational Oncology Research, Greenville, South Carolina.
7
Comprehensive Cancer Centers of Nevada and U.S. Oncology Research, Las Vegas, Nevada.
8
Lynn Cancer Institute, Boca Raton, Florida.
9
Urology Cancer Center and GU Research Network, Omaha, Nebraska.
10
Greenville Hospital System and University Medical Center, Greenville, South Carolina.
11
Tokai Pharmaceuticals, Cambridge, Massachusetts.
12
Dana-Farber Cancer Institute, Boston, Massachusetts. Mary_Taplin@dfci.harvard.edu.

Abstract

PURPOSE:

Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study.

EXPERIMENTAL DESIGN:

In ARMOR1, 49 patients received increasing doses (650-2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700-3,400 mg) of galeterone in tablet formulation for 12 weeks. Patients were evaluated biweekly for safety and efficacy, and pharmacokinetic parameters were assessed.

RESULTS:

In ARMOR1, across all doses, 49.0% (24/49) achieved a ≥30% decline in prostate-specific antigen (PSA; PSA30) and 22.4% (11/49) demonstrated a ≥50% PSA decline (PSA50). In ARMOR2 part 1, across all doses, PSA30 was 64.0% (16/25) and PSA50 was 48.0% (12/25). In the 2,550-mg dose cohort, PSA30 was 72.7% (8/11) and PSA50 was 54.5% (6/11). Galeterone was well tolerated; the most common adverse events were fatigue, increased liver enzymes, gastrointestinal events, and pruritus. Most were mild or moderate in severity and required no action and there were no apparent mineralocorticoid excess (AME) events.

CONCLUSIONS:

The efficacy and safety from ARMOR1 and ARMOR2 part 1 and the pharmacokinetic results support the galeterone tablet dose of 2,550 mg/d for further study. Galeterone was well tolerated and demonstrated pharmacodynamic changes consistent with its selective, multifunctional AR signaling inhibition.

PMID:
26527750
DOI:
10.1158/1078-0432.CCR-15-1432
[Indexed for MEDLINE]
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