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A phase II study of the HDAC inhibitor SB939 in patients with castration resistant prostate cancer: NCIC clinical trials group study IND195

  • PHASE II STUDIES
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Summary

Background SB939 is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDACs). These three HDAC classes are highly expressed in castration resistant prostate cancer (CRPC) and associated with poor clinical outcomes. We designed a phase II study of SB939 in men with metastatic CRPC. Methods Patients received SB939 60 mg on alternate days three times per week for 3 weeks on a 4-week cycle. Primary endpoints were PSA response rate (RR) and progression-free survival (PFS). Secondary endpoints included objective response rate and duration; overall survival; circulating tumor cell (CTC) enumeration and safety. Exploratory correlative studies of the TMPRSS2-ERG fusion and PTEN biomarkers were also performed. Results Thirty-two patients were enrolled of whom 88 % had received no prior chemotherapy. The median number of SB939 cycles administered was three (range 1–8). Adverse events were generally grade 1–2, with five pts experiencing one or more grade three event. One patient died due to myocardial infarction. A confirmed PSA response was noted in two pts (6 %), lasting 3.0 and 21.6 months. In patients with measurable disease there were no objective responses. Six patients had stable disease lasting 1.7 to 8.0 months. CTC response (from ≥5 at baseline to <5 at 6 or 12 weeks) occurred in 9/14 evaluable patients (64 %). Conclusion Although SB939 was tolerable at the dose/schedule given, and showed declines in CTC in the majority of evaluable patients, it did not show sufficient activity based on PSA RR to warrant further study as a single agent in unselected patients with CRPC.

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Acknowledgments

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society Research Institute (grant #021039) l

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. BC Cancer Agency, Vancouver, BC, Canada

    B. J. Eigl & K. N. Chi

  2. Cross Cancer Institute, Edmonton, AB, Canada

    S. North

  3. London Health Sciences Centre, London, ON, Canada

    E. Winquist

  4. BC Cancer Agency, Kelowna, BC, Canada

    D. Finch

  5. QEII Health Sciences Centre, Halifax, NS, Canada

    L. Wood

  6. Princess Margaret Cancer Centre, Toronto, ON, Canada

    S. S. Sridhar

  7. NCIC Clinical Trials Group, Kingston, ON, Canada

    J. Powers, P. A. Bradbury & E. A. Eisenhauer

  8. Queens University, Kingston, ON, Canada

    J. Good, J. A. Squire & T. Jamaspishvili

  9. Vancouver Prostate Centre, Vancouver, BC, Canada

    M. Sharma, J. Bazov & M. E. Cox

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  1. B. J. Eigl
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  2. S. North
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  10. J. A. Squire
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  14. P. A. Bradbury
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  15. E. A. Eisenhauer
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Corresponding author

Correspondence to B. J. Eigl.

Additional information

PAB is funded by a Cancer Care Ontario Research Chair in Experimental Therapeutics

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Eigl, B.J., North, S., Winquist, E. et al. A phase II study of the HDAC inhibitor SB939 in patients with castration resistant prostate cancer: NCIC clinical trials group study IND195. Invest New Drugs 33, 969–976 (2015). https://doi.org/10.1007/s10637-015-0252-4

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  • DOI: https://doi.org/10.1007/s10637-015-0252-4

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