A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA)

doi:10.1186/s12885-019-5805-z

. 2019 Jun 13;19(1):572.

doi: 10.1186/s12885-019-5805-z.

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA)

Roche Kapoor¹, Matthew P Deek¹, Riley McIntyre¹, Natasha Raman¹, Megan Kummerlowe¹, Iyah Chen¹, Matt Gaver¹, Hao Wang², Sam Denmeade^{2

3}, Tamara Lotan⁴, Channing Paller^{2

3}, Mark Markowski², Michael Carducci^{2

3}, Mario Eisenberger^{2

3}, Tomasz M Beer⁵, Daniel Y Song^{1

2

3}, Theodore L DeWeese^{1

2

3}, Jason W Hearn⁶, Stephen Greco¹, Curtiland DeVille¹, Neil B Desai⁷, Elisabeth I Heath⁸, Stanley Liauw⁹, Daniel E Spratt⁶, Arthur Y Hung¹⁰, Emmanuel S Antonarakis¹¹, Phuoc T Tran^{12

13

14}

Affiliations

¹ Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1550 Orleans Street, CRB2 Rm 406, Baltimore, MD, 21231, USA.
² Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1650 Orleans Street, CRB1 Rm 1M45, Baltimore, MD, 21231, USA.
³ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
⁶ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁸ Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
⁹ Department of Radiation Oncology and Cellular Oncology, University of Chicago, Chicago, IL, USA.
¹⁰ Department of Radiation Medicine, OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
¹¹ Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1650 Orleans Street, CRB1 Rm 1M45, Baltimore, MD, 21231, USA. eantona1@jhmi.edu.
¹² Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1550 Orleans Street, CRB2 Rm 406, Baltimore, MD, 21231, USA. Tranp@jhmi.edu.
¹³ Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1650 Orleans Street, CRB1 Rm 1M45, Baltimore, MD, 21231, USA. Tranp@jhmi.edu.
¹⁴ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Tranp@jhmi.edu.

PMID: 31196032
PMCID: PMC6567492
DOI: 10.1186/s12885-019-5805-z

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA)

Roche Kapoor et al. BMC Cancer. 2019.

. 2019 Jun 13;19(1):572.

doi: 10.1186/s12885-019-5805-z.

Authors

Affiliations

¹ Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1550 Orleans Street, CRB2 Rm 406, Baltimore, MD, 21231, USA.
² Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1650 Orleans Street, CRB1 Rm 1M45, Baltimore, MD, 21231, USA.
³ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
⁶ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁸ Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
⁹ Department of Radiation Oncology and Cellular Oncology, University of Chicago, Chicago, IL, USA.
¹⁰ Department of Radiation Medicine, OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
¹¹ Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1650 Orleans Street, CRB1 Rm 1M45, Baltimore, MD, 21231, USA. eantona1@jhmi.edu.
¹² Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1550 Orleans Street, CRB2 Rm 406, Baltimore, MD, 21231, USA. Tranp@jhmi.edu.
¹³ Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1650 Orleans Street, CRB1 Rm 1M45, Baltimore, MD, 21231, USA. Tranp@jhmi.edu.
¹⁴ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Tranp@jhmi.edu.

PMID: 31196032
PMCID: PMC6567492
DOI: 10.1186/s12885-019-5805-z

Abstract

Background: In men with a rising PSA following radical prostatectomy, salvage radiation therapy (SRT) offers a second chance for cure. Hormonal therapy can be combined with SRT in order to increase prostate tumor control, albeit with associated higher rates of treatment side effects. This trial studies the effectiveness of SRT combined with hormonal therapy using a more potent anti-androgen with a favorable side effect profile. Enzalutamide, a next generation selective androgen receptor antagonist, is approved by the Food and Drug Administration for the treatment of metastatic castrate-resistant prostate cancer (CRPC) where it has been shown to improve overall survival in combination with androgen deprivation therapy. The primary objective of this study is to evaluate the efficacy of combination SRT and enzalutamide for freedom-from-PSA-progression. Secondary objectives include time to local recurrence within the radiation field, metastasis-free survival and safety as determined by frequency and severity of adverse events.

Methods/design: This is a randomized, double-blind, phase II, prospective, multicenter study in adult males with biochemically recurrent prostate cancer following radical prostatectomy. Following registration, enzalutamide 160 mg or placebo by mouth (PO) once daily will be administered for 6 months. Following two months of study drug, external beam radiotherapy to 66.6-70.2 Gray (Gy) will be administered to the prostate bed over 7-8 weeks while continuing daily placebo/enzalutamide. This is followed by two additional months of placebo/enzalutamide.

Discussion: The SALV-ENZA trial is the first phase II placebo-controlled double-blinded randomized study to test SRT in combination with a next generation androgen receptor antagonist in men with high-risk recurrent prostate cancer after radical prostatectomy. The primary hypothesis of this study is that clinical outcomes will be improved by the addition of enzalutamide compared to standard-of-care SRT alone and pave the path for phase III evaluation of this combination.

Trial registrations: ClinicaltTrials.gov Identifier: NCT02203695 Date of Registration: 06/16/2014. Date of First Participant Enrollment: 04/16/2015.

Keywords: Enzalutamide; High-risk prostate cancer; Prostatectomy; Recurrent prostate cancer; Salvage radiation therapy (SRT).

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
SALV-ENZA Study Schema. Subjects who meet eligibility criteria and qualify for enrollment will be stratified and randomized as demonstrated

See this image and copyright information in PMC

Cited by

Should androgen deprivation therapy and other systemic treatments be used in men with prostate cancer and a rising PSA post-local treatments?
Patrikidou A, Zilli T, Baciarello G, Terisse S, Hamilou Z, Fizazi K. Patrikidou A, et al. Ther Adv Med Oncol. 2021 Oct 20;13:17588359211051870. doi: 10.1177/17588359211051870. eCollection 2021. Ther Adv Med Oncol. 2021. PMID: 34707693 Free PMC article. Review.

References

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1. D'Amico AV, Chen MH, Catalona WJ, Sun L, Roehl KA, Moul JW. Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors. Cancer. 2007;110(1):56–61. doi: 10.1002/cncr.22737. - DOI - PubMed

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[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30. doi: 10.3322/caac.21442. - DOI - PubMed

[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30. doi: 10.3322/caac.21442. - DOI - PubMed

[3] Spratt DE, Dess RT, Zumsteg ZS, Lin DW, Tran PT, Morgan TM, Antonarakis ES, Nguyen PL, Ryan CJ, Sandler HM, et al. A systematic review and framework for the use of hormone therapy with salvage radiation therapy for recurrent prostate Cancer. Eur Urol. 2018;73(2):156–165. doi: 10.1016/j.eururo.2017.06.027. - DOI - PubMed

[4] Spratt DE, Dess RT, Zumsteg ZS, Lin DW, Tran PT, Morgan TM, Antonarakis ES, Nguyen PL, Ryan CJ, Sandler HM, et al. A systematic review and framework for the use of hormone therapy with salvage radiation therapy for recurrent prostate Cancer. Eur Urol. 2018;73(2):156–165. doi: 10.1016/j.eururo.2017.06.027. - DOI - PubMed

[5] Anscher MS, Clough R, Robertson CN, Prosnitz LR, Dahm P, Walther P, Donatucci CF, Albala DM, Febbo P, George DJ, et al. Timing and patterns of recurrences and deaths from prostate cancer following adjuvant pelvic radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate. Prostate Cancer Prostatic Dis. 2006;9(3):254–260. doi: 10.1038/sj.pcan.4500903. - DOI - PubMed

[6] Anscher MS, Clough R, Robertson CN, Prosnitz LR, Dahm P, Walther P, Donatucci CF, Albala DM, Febbo P, George DJ, et al. Timing and patterns of recurrences and deaths from prostate cancer following adjuvant pelvic radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate. Prostate Cancer Prostatic Dis. 2006;9(3):254–260. doi: 10.1038/sj.pcan.4500903. - DOI - PubMed

[7] Carver BS, Bianco FJ, Jr, Scardino PT, Eastham JA. Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer. J Urol. 2006;176(2):564–568. doi: 10.1016/j.juro.2006.03.093. - DOI - PubMed

[8] Carver BS, Bianco FJ, Jr, Scardino PT, Eastham JA. Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer. J Urol. 2006;176(2):564–568. doi: 10.1016/j.juro.2006.03.093. - DOI - PubMed

[9] D'Amico AV, Chen MH, Catalona WJ, Sun L, Roehl KA, Moul JW. Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors. Cancer. 2007;110(1):56–61. doi: 10.1002/cncr.22737. - DOI - PubMed

[10] D'Amico AV, Chen MH, Catalona WJ, Sun L, Roehl KA, Moul JW. Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors. Cancer. 2007;110(1):56–61. doi: 10.1002/cncr.22737. - DOI - PubMed

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A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA)

Affiliations

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA)

Authors

Affiliations

Abstract

Conflict of interest statement

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