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Clinical Trials in CRPC

  • Yoon Seok Suh
  • Jae Young Joung
Chapter

Abstract

Prostate cancer (PC) is the second most common cause of cancer-related mortality in US men, and 180,890 of new PC cases occurred in 2016 [1]. At the time of diagnosis, approximately 12% of patients had locally advanced PC, and about 4% of patients had PC with metastasis [2]. Cure for localized PC that is newly diagnosed is available with definitive therapy. However, almost 30% of patients with PC experience recurrence of PC and castration-resistant PC (CRPC) [2]. Many new drugs have been approved by the US Food and Drug Administration (FDA) as a therapeutic option for CRPC. Various pathways and targets have demonstrated major advances in understanding the mechanisms of acquiring castration resistance and showing progression of PC. In this chapter, the clinical trials in CRPC will be elaborated. A large number of new agents for CRPC that is based on various mechanisms are currently being studied worldwide. Clinical trials of CRPC are summarized in Table 24.1.

Keywords

Prostate cancer Castration-resistant Clinical trial Drug CRPC 

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.CrossRefGoogle Scholar
  2. 2.
    Shore ND. Radium-223 dichloride for metastatic castration-resistant prostate cancer: the urologist's perspective. Urology. 2015;85(4):717–24.CrossRefPubMedGoogle Scholar
  3. 3.
    Ross RW, Beer TM, Jacobus S, Bubley GJ, Taplin ME, Ryan CW, et al. A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel. Cancer. 2008;112(3):521–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Fury MG, Sherman E, Haque S, Korte S, Lisa D, Shen R, et al. A phase I study of daily everolimus plus low-dose weekly cisplatin for patients with advanced solid tumors. Cancer Chemother Pharmacol. 2012;69(3):591–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Vaishampayan U, Shevrin D, Stein M, Heilbrun L, Land S, Stark K, et al. Phase II trial of carboplatin, everolimus, and prednisone in metastatic castration-resistant prostate cancer pretreated with docetaxel chemotherapy: a prostate cancer clinical trial consortium study. Urology. 2015;86(6):1206–11.CrossRefPubMedGoogle Scholar
  6. 6.
    Brand LJ, Olson ME, Ravindranathan P, Guo H, Kempema AM, Andrews TE, et al. EPI-001 is a selective peroxisome proliferator-activated receptor-gamma modulator with inhibitory effects on androgen receptor expression and activity in prostate cancer. Oncotarget. 2015;6(6):3811.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Maughan BL, Antonarakis ES. Clinical relevance of androgen receptor splice variants in castration-resistant prostate cancer. Curr Treat Options in Oncol. 2015;16(12):57.CrossRefGoogle Scholar
  8. 8.
    Fizazi K, Massard C, Bono P, Jones R, Kataja V, James N, et al. Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Lancet Oncol. 2014;15(9):975–85.CrossRefPubMedGoogle Scholar
  9. 9.
    Montgomery B, Eisenberger MA, Rettig MB, Chu F, Pili R, Stephenson JJ, et al. Androgen receptor modulation optimized for response (ARMOR) phase I and II studies: galeterone for the treatment of castration-resistant prostate cancer. Clin Cancer Res. 2016;22(6):1356–63.CrossRefPubMedGoogle Scholar
  10. 10.
    Loriot Y, Fizazi K, Jones RJ, Van den Brande J, Molife RL, Omlin A, et al. Safety, tolerability and anti-tumour activity of the androgen biosynthesis inhibitor ASP9521 in patients with metastatic castration-resistant prostate cancer: multi-centre phase I/II study. Investig New Drugs. 2014;32(5):995–1004.CrossRefGoogle Scholar
  11. 11.
    Toren PJ, Kim S, Pham S, Mangalji A, Adomat H, Guns EST, et al. Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer. Mol Cancer Ther. 2015;14(1):59–69.CrossRefPubMedGoogle Scholar
  12. 12.
    Falchook GS, Zhou X, Venkatakrishnan K, Kurzrock R, Mahalingam D, Goldman JW, et al. Effect of food on the pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. Drugs R&D. 2016;16(1):45–52.CrossRefGoogle Scholar
  13. 13.
    Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 2011;1(6):487–95.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Sowery RD, Hadaschik BA, So AI, Zoubeidi A, Fazli L, Hurtado-Coll A, et al. Clusterin knockdown using the antisense oligonucleotide OGX-011 re-sensitizes docetaxel-refractory prostate cancer PC-3 cells to chemotherapy. BJU Int. 2008;102(3):389–97.CrossRefPubMedGoogle Scholar
  15. 15.
    Chi KN, Hotte SJ, Yu EY, Tu D, Eigl BJ, Tannock I, et al. Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(27):4247–54.CrossRefPubMedGoogle Scholar
  16. 16.
    Chow H, Ghosh PM, de Vere White R, Evans CP, Dall’Era MA, Yap SA, et al. A phase 2 clinical trial of everolimus plus bicalutamide for castration-resistant prostate cancer. Cancer. 2016;122(12):1897–904.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Pili R, Häggman M, Stadler WM, Gingrich JR, Assikis VJ, Björk A, et al. Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. J Clin Oncol. 2011;29(30):4022–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Lamoureux F, Zoubeidi A. Dual inhibition of autophagy and the AKT pathway in prostate cancer. Autophagy. 2013;9(7):1119–20.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Gravina GL, Mancini A, Sanita P, Vitale F, Marampon F, Ventura L, et al. KPT-330, a potent and selective exportin-1 (XPO-1) inhibitor, shows antitumor effects modulating the expression of cyclin D1 and survivin in prostate cancer models. BMC Cancer. 2015;15(1):941.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, et al. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol. 2012;31(4):412–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kim RH, Coates JM, Bowles TL, McNerney GP, Sutcliffe J, Jung JU, et al. Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Res. 2009;69(2):700–8.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Tomlinson BK, Thomson JA, Bomalaski JS, Diaz M, Akande T, Mahaffey N, et al. Phase I trial of arginine deprivation therapy with ADI-PEG 20 plus docetaxel in patients with advanced malignant solid tumors. Clin Cancer Res. 2015;Google Scholar
  23. 23.
    Podrazil M, Horvath R, Becht E, Rozkova D, Bilkova P, Sochorova K, et al. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer. Oncotarget. 2015;6(20):18192.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(7):1099–105.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    McNeel DG, Chen Y-H, Gulley JL, Dwyer AJ, Madan RA, Carducci MA, et al. Randomized phase II trial of docetaxel with or without PSA-TRICOM vaccine in patients with castrate-resistant metastatic prostate cancer: A trial of the ECOG-ACRIN cancer research group (E1809). Hum Vaccin Immunother. 2015;11(10):2469–74.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Fenoglio D, Traverso P, Parodi A, Tomasello L, Negrini S, Kalli F, et al. A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer. Cancer Immunol Immunother. 2013;62(6):1041–52.CrossRefPubMedGoogle Scholar
  27. 27.
    DiPippo VA, Olson WC, Nguyen HM, Brown LG, Vessella RL, Corey E. Efficacy studies of an antibody-drug conjugate PSMA-ADC in patient-derived prostate cancer xenografts. Prostate. 2015;75(3):303–13.CrossRefPubMedGoogle Scholar
  28. 28.
    Chakraborty M, Abrams SI, Camphausen K, Liu K, Scott T, Coleman CN, et al. Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J Immunol. 2003;170(12):6338–47.CrossRefPubMedGoogle Scholar
  29. 29.
    Slovin S, Higano C, Hamid O, Tejwani S, Harzstark A, Alumkal J, et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013;24(7):1813–21.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, Van den Eertwegh AJ, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700–12.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;2015(373):1697–708.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Yoon Seok Suh
    • 1
  • Jae Young Joung
    • 1
  1. 1.Department of Urology, Center for Prostate CancerResearch Institute and Hospital, National Cancer CenterGoyangKorea

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