Investigational New Drugs

, Volume 36, Issue 2, pp 278–287 | Cite as

A randomized phase 2 study of a HSP27 targeting antisense, apatorsen with prednisone versus prednisone alone, in patients with metastatic castration resistant prostate cancer

  • Evan Y. Yu
  • Susan L. Ellard
  • Sebastien J. Hotte
  • Joel R. Gingerich
  • Anthony M. Joshua
  • Martin E. Gleave
  • Kim N. Chi
PHASE II STUDIES

Summary

Purpose Heat shock protein 27 (Hsp27) is implicated in prostate cancer progression. Apatorsen is a second generation phosphorothioate antisense inhibitor of Hsp27 expression. We evaluated apatorsen in patients with metastatic castration resistant prostate cancer (mCRPC). Experimental design Eligible patients were randomized 1:1 to receive intravenous apatorsen (3 loading doses of 600 mg within 5–9 days followed by weekly doses of 1000 mg) with oral prednisone 5 mg twice daily or prednisone alone. The primary endpoint was disease progression at 12 weeks. Crossover from prednisone alone was allowed after radiographic progression. Results 74 patients received apatorsen + prednisone (n = 36) or prednisone alone (n = 38). Twenty-five patients crossed-over to receive apatorsen + prednisone. Apatorsen treated patients received a median of 19 infusions. 50% of apatorsen + prednisone patients (95% CI: 32.9%, 67.1%) compared with 42% of prednisone patients (95% CI: 26.3%, 59.2%) did not have disease progression at week 12 (P = 0.33). A PSA decline of ≥50% was observed in 47% of apatorsen + prednisone and 24% of prednisone patients (P = 0.04), with a median duration of response of 24.1 weeks (95% CI: 12.0, 52) and 14.0 weeks (95% CI: 4.0, 44.4), respectively. A PSA decline of ≥50% was observed in 5 patients (20%) that received cross-over apatorsen. Infusion reactions were the most commonly reported adverse event occurring in 77% of apatorsen-treated patients. Conclusions Apatorsen + prednisone did not change the proportion of CRPC patients without disease progression at 12 weeks compared to prednisone but was associated with significant PSA declines. Further evaluation of Hsp27 targeting in prostate cancer is warranted.

Keywords

Heat shock protein 27 Prostate cancer Castration-resistant Randomized phase 2 Clinical trial 

Notes

Compliance with ethical standards

Conflict of interest

The institution of EYY received funding from OncoGeneX Pharmaceuticals, Inc. to aid in performance of the submitted research. The University of British Columbia has licensed patent applications on OGX-427, listing MEG as inventor, to OncoGenex Technologies, a Vancouver-based biotechnology company that MEG has founding shares in. Otherwise, there are no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Evan Y. Yu
    • 1
    • 2
  • Susan L. Ellard
    • 3
  • Sebastien J. Hotte
    • 4
  • Joel R. Gingerich
    • 5
  • Anthony M. Joshua
    • 6
    • 7
    • 8
  • Martin E. Gleave
    • 9
  • Kim N. Chi
    • 3
    • 10
  1. 1.Division of Oncology, Department of MedicineUniversity of Washington School of MedicineSeattleUSA
  2. 2.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  3. 3.Division of Medical Oncology, Department of MedicineUniversity of British ColumbiaVancouverCanada
  4. 4.Division of Medical Oncology, Department of OncologyMcMaster UniversityHamiltonCanada
  5. 5.Division of Medical Oncology, Cancer Care ManitobaUniversity of ManitobaWinnipegCanada
  6. 6.Kinghorn Cancer CenterSt Vincents HospitalSydneyAustralia
  7. 7.Faculty of MedicineUniversity of New South WalesSydneyAustralia
  8. 8.Princess Margaret Cancer CentreTorontoCanada
  9. 9.Department of Urologic Sciences, Vancouver Prostate CentreUniversity of British ColumbiaVancouverCanada
  10. 10.BC Cancer AgencyVancouverCanada

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