Androgen Receptor Modulation Optimized for Response (ARMOR) phase i and II studies: Galeterone for the treatment of castration-resistant prostate cancer

Clinical Cancer Research

Volumn 22, Issue 6, 2016, Pages 1356-1363

  Montgomery, Bruce ^a   Eisenberger, Mario A ^b   Rettig, Matthew B ^c   Chu, Franklin ^d   Pili, Roberto ^e   Stephenson, Joseph J ^f   Vogelzang, Nicholas J ^g   Koletsky, Alan J ^h   Nordquist, Luke T ⁱ   Edenfield, William J ^j   Mamlouk, Khalid ^k   Ferrante, Karen J ^k   Taplin, Mary Ellen ^l  

^a UNIVERSITY OF WASHINGTON   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d San Bernadino Urological Associates   (United States)

^e INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f Institute for Translational Oncology Research   (United States)

^g US Oncology Research ^*  (United States)

^h Lynn Cancer Institute   (United States)

ⁱ Urology Cancer Center   (United States)

^j GREENVILLE HOSPITAL SYSTEM   (United States)

^k Tokai Pharmaceuticals Inc   (United States)

^l DANA FARBER CANCER INSTITUTE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ANDROGEN RECEPTOR; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; GALETERONE; MINERALOCORTICOID; PROSTATE SPECIFIC ANTIGEN; 3-HYDROXY-17-(1H-BENZIMIDAZOLE-1-YL)ANDROSTA-5,16-DIENE; ANDROSTANE DERIVATIVE; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS; BENZIMIDAZOLE DERIVATIVE;

ABDOMINAL PAIN; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BACKACHE; BILIRUBIN BLOOD LEVEL; BODY WEIGHT; CASTRATION RESISTANT PROSTATE CANCER; CLINICAL ARTICLE; CONSTIPATION; COUGHING; DECREASED APPETITE; DIARRHEA; DISEASE SEVERITY; DIZZINESS; DRUG CAPSULE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EVENING DOSAGE; FATIGUE; GASTROINTESTINAL SYMPTOM; HUMAN; HYPOKALEMIA; MALE; MORNING DOSAGE; MULTICENTER STUDY; NAUSEA; PERIPHERAL EDEMA; PHARMACOKINETIC PARAMETERS; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; SIDE EFFECT; TABLET FORMULATION; URINARY TRACT INFECTION; VOMITING; AGED; CANCER STAGING; CLINICAL TRIAL; DRUG EFFECTS; METABOLISM; METASTASIS; MIDDLE AGED; MULTIMODALITY CANCER THERAPY; PATHOLOGY; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; RETREATMENT; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANDROSTADIENES; ANTINEOPLASTIC AGENTS, HORMONAL; BENZIMIDAZOLES; COMBINED MODALITY THERAPY; HUMANS; MALE; MIDDLE AGED; NEOPLASM METASTASIS; NEOPLASM STAGING; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; RECEPTORS, ANDROGEN; RETREATMENT; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84962218644     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-1432     Document Type: Article

References (33)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.
2. Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008;68:4447-54.
3. Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res 2008;68: 6407-15.
4. Dillard PR, Lin MF, Khan SA. Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol. Mol Cell Endocrinol 2008;295:115-20.
5. Chang KH, Li R, Papari-Zareei M, Watumull L, Zhao YD, Auchus RJ, et al. Dihydrotestosterone synthesis bypasses testosterone to drive castrationresistant prostate cancer. Proc Natl Acad Sci U S A 2011;108:13728-33.
6. Edwards J, Krishna NS, Grigor KM, Bartlett JM. Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br J Cancer 2003;89:552-6.
7. Linja MJ, Porkka KP, Kang Z, Savinainen KJ, Janne OA, Tammela TL, et al. Expression of androgen receptor coregulators in prostate cancer. Clin Cancer Res 2004;10:1032-40.
8. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368:138-48.
9. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005.
10. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187-97.
11. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371:424-33.
12. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014;371:1028-38.
13. Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol 2015;67:53-60.
14. Joseph JD, Lu N, Qian J, Sensintaffar J, Shao G, BrighamD, et al. A clinically relevant androgen receptormutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov 2013;3:1020-9.
15. Guo Z, Yang X, Sun F, Jiang R, Linn DE, Chen H, et al. A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res 2009;69: 2305-13.
16. Mostaghel EA, Plymate SR, Montgomery B. Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit. Clin Cancer Res 2014;20:791-8.
17. Brooke GN, Bevan CL. The role of androgen receptor mutations in prostate cancer progression. Curr Genomics 2009;10:18-25.
18. Taplin ME. Drug insight: role of the androgen receptor in the development and progression of prostate cancer. Nat Clin Pract Oncol 2007;4:236-44.
19. Carreira S, Romanel A, Goodall J, Grist E, Ferraldeschi R, et al. Tumor clone dynamics in lethal prostate cancer. Science Translational Medicine 2014; 254:ra125
20. Jacoby D, Williams M. Differenential effects of galeterone, abiraterone, orteronel, and ketoconazole on CYP17 and steroidogenesis. J Clin Oncol 2013. Abstr 184.
21. Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, et al. Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. JMed Chem 2005;48: 2972-84.
22. Vasaitis T, Belosay A, Schayowitz A, Khandelwal A, Chopra P, Gediya LK, et al. Androgen receptor inactivation contributes to antitumor efficacy of 17a-hydroxylase/17,20-lyase inhibitor 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene in prostate cancer. Mol Cancer Ther 2008;7:2348-57.
23. Schayowitz A, Sabnis G, Njar VC, Brodie AM. Synergistic effect of a novel antiandrogen, VN/124-1, and signal transduction inhibitors in prostate cancer progression to hormone independence in vitro. Mol Cancer Ther 2008;7:121-32.
24. Purushottamachar P, Godbole AM, Gediya LK, Martin MS, Vasaitis TS, Kwegyir-Afful AK, et al. Systematic structure modifications of multitarget prostate cancer drug candidate galeterone to produce novel androgen receptor down-regulating agents as an approach to treatment of advanced prostate cancer. J Med Chem 2013;56:4880-98.
25. Bruno RD, Vasaitis TS,Gediya LK, Purushottamachar P, Godbole AM, Ates- Alagoz Z, et al. Synthesis and biological evaluations of putative metabolically stable analogs of VN/124-1 (TOK-001): head to head anti-tumor efficacy evaluation of VN/124-1 (TOK-001) and abiraterone in LAPC-4 human prostate cancer xenograft model. Steroids 2011;76:1268-79.
26. Kwegyir-Afful AK, Senthilmurugan R, Purushottamachar P, Ramamurthy VP, Njar VCO. Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration-resistant prostate cancer xenografts in vivo. Oncogarget 2015;6:27440-27460.
27. AlNakouzi N, Wang C, Jacoby D, Gleave ME, Zoubeidi A. Galeterone suppresses castration-resistant and enzalutamide-resistant prostate cancer growth in vitro [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, Massachusetts: AACR; 2013. Abstract nr C89.
28. Kramer WG, Vince B, McGarry C. Comparison of the pharmacokinetics (PK) of galeterone novel oral formulation. J Clin Oncol 2013;Supplement: e16075.
29. Bubley GJ, Carducci M, Dahut W, Dawson N, Daliani D, Eisenberger M, et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate- Specific Antigen Working Group. J Clin Oncol 1999;17:3461-7.
30. Scher HI, Morris MJ, Basch E, Heller G. End points and outcomes in castration-resistant prostate cancer: from clinical trials to clinical practice. J Clin Oncol 2011;29:3695-704.
31. Ryan CJ, Smith MR, Fong L, Rosenberg JE, Kantoff P, Raynaud F, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol 2010;28:1481-8.
32. TOK-200-09 Clinical Study Report. Tokai Pharmaceuticals; 2013.
33. Taplin ME, Chi KN, Chu F, Cochran J, Edenfield WJ, Eisenberger M, et al. Galeterone in 4 patient populations of men with CRPC: results from ARMOR2 [abstract]. In: Proceedings of the European Society of Medical Oncology Annual Meeting; 2014 Sep 26-30, 2014; Madrid, Spain: ESMO; 2014. Abstract nr 757O.