Androgen Receptor Modulation Optimized for Response (ARMOR) phase i and II studies

Galeterone for the treatment of castration-resistant prostate cancer

Bruce Montgomery, Mario A. Eisenberger, Matthew B. Rettig, Franklin Chu, Roberto Pili, Joseph J. Stephenson, Nicholas J. Vogelzang, Alan J. Koletsky, Luke T. Nordquist, William J. Edenfield, Khalid Mamlouk, Karen J. Ferrante, Mary Ellen Taplin

Research output: Contribution to journalArticle

40 Citations (Scopus)

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: InARMOR1, 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 ormoderate 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.

Original languageEnglish (US)
Pages (from-to)1356-1363
Number of pages8
JournalClinical Cancer Research
Volume22
Issue number6
DOIs
StatePublished - Mar 15 2016

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Castration
Androgen Receptors
Prostatic Neoplasms
Safety
Therapeutics
Tablets
Pharmacokinetics
Steroid 17-alpha-Hydroxylase
Pruritus
Prostate-Specific Antigen
3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene
Proteolysis
Capsules
Fatigue
Research Design
Liver
Enzymes

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Androgen Receptor Modulation Optimized for Response (ARMOR) phase i and II studies : Galeterone for the treatment of castration-resistant prostate cancer. / Montgomery, Bruce; Eisenberger, Mario A.; Rettig, Matthew B.; Chu, Franklin; Pili, Roberto; Stephenson, Joseph J.; Vogelzang, Nicholas J.; Koletsky, Alan J.; Nordquist, Luke T.; Edenfield, William J.; Mamlouk, Khalid; Ferrante, Karen J.; Taplin, Mary Ellen.

In: Clinical Cancer Research, Vol. 22, No. 6, 15.03.2016, p. 1356-1363.

Research output: Contribution to journalArticle

Montgomery, B, Eisenberger, MA, Rettig, MB, Chu, F, Pili, R, Stephenson, JJ, Vogelzang, NJ, Koletsky, AJ, Nordquist, LT, Edenfield, WJ, Mamlouk, K, Ferrante, KJ & Taplin, ME 2016, 'Androgen Receptor Modulation Optimized for Response (ARMOR) phase i and II studies: Galeterone for the treatment of castration-resistant prostate cancer', Clinical Cancer Research, vol. 22, no. 6, pp. 1356-1363. https://doi.org/10.1158/1078-0432.CCR-15-1432
Montgomery, Bruce ; Eisenberger, Mario A. ; Rettig, Matthew B. ; Chu, Franklin ; Pili, Roberto ; Stephenson, Joseph J. ; Vogelzang, Nicholas J. ; Koletsky, Alan J. ; Nordquist, Luke T. ; Edenfield, William J. ; Mamlouk, Khalid ; Ferrante, Karen J. ; Taplin, Mary Ellen. / Androgen Receptor Modulation Optimized for Response (ARMOR) phase i and II studies : Galeterone for the treatment of castration-resistant prostate cancer. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 6. pp. 1356-1363.
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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: InARMOR1, 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 ormoderate 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.",
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T2 - Galeterone for the treatment of castration-resistant prostate cancer

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AU - Eisenberger, Mario A.

AU - Rettig, Matthew B.

AU - Chu, Franklin

AU - Pili, Roberto

AU - Stephenson, Joseph J.

AU - Vogelzang, Nicholas J.

AU - Koletsky, Alan J.

AU - Nordquist, Luke T.

AU - Edenfield, William J.

AU - Mamlouk, Khalid

AU - Ferrante, Karen J.

AU - Taplin, Mary Ellen

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N2 - 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: InARMOR1, 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 ormoderate 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.

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