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, Matthew P. Deek, Riley McIntyre, Natasha Raman, Megan Kummerlowe, Iyah Chen, Matt Gaver, Hao Wang, Sam Denmeade, Tamara Lotan, Channing Paller, Mark Markowski, Michael Carducci, Mario Eisenberger, Tomasz (Tom) Beer, Daniel Y. Song, Theodore L. Deweese, Jason W. Hearn, Stephen Greco, Curtiland DevilleNeil B. Desai, Elisabeth I. Heath, Stanley Liauw, Daniel E. Spratt, Arthur Hung, Emmanuel S. Antonarakis, Phuoc T. Tran

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number572
JournalBMC cancer
Volume19
Issue number1
DOIs
StatePublished - Jun 13 2019

Fingerprint

Salvage Therapy
Prostatectomy
Double-Blind Method
Prostatic Neoplasms
Radiotherapy
Placebos
Androgen Receptor Antagonists
Androgens
Prostate
Therapeutics
Survival
United States Food and Drug Administration
Standard of Care
MDV 3100
Multicenter Studies
Mouth
Prospective Studies
Radiation
Neoplasm Metastasis
Safety

Keywords

  • Enzalutamide
  • High-risk prostate cancer
  • Prostatectomy
  • Recurrent prostate cancer
  • Salvage radiation therapy (SRT)

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

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). / Kapoor, Roche; Deek, Matthew P.; McIntyre, Riley; Raman, Natasha; Kummerlowe, Megan; Chen, Iyah; Gaver, Matt; Wang, Hao; Denmeade, Sam; Lotan, Tamara; Paller, Channing; Markowski, Mark; Carducci, Michael; Eisenberger, Mario; Beer, Tomasz (Tom); Song, Daniel Y.; Deweese, Theodore L.; Hearn, Jason W.; Greco, Stephen; Deville, Curtiland; Desai, Neil B.; Heath, Elisabeth I.; Liauw, Stanley; Spratt, Daniel E.; Hung, Arthur; Antonarakis, Emmanuel S.; Tran, Phuoc T.

In: BMC cancer, Vol. 19, No. 1, 572, 13.06.2019.

Research output: Contribution to journalArticle

Kapoor, R, Deek, MP, McIntyre, R, Raman, N, Kummerlowe, M, Chen, I, Gaver, M, Wang, H, Denmeade, S, Lotan, T, Paller, C, Markowski, M, Carducci, M, Eisenberger, M, Beer, TT, Song, DY, Deweese, TL, Hearn, JW, Greco, S, Deville, C, Desai, NB, Heath, EI, Liauw, S, Spratt, DE, Hung, A, Antonarakis, ES & Tran, PT 2019, '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)', BMC cancer, vol. 19, no. 1, 572. https://doi.org/10.1186/s12885-019-5805-z
Kapoor, Roche ; Deek, Matthew P. ; McIntyre, Riley ; Raman, Natasha ; Kummerlowe, Megan ; Chen, Iyah ; Gaver, Matt ; Wang, Hao ; Denmeade, Sam ; Lotan, Tamara ; Paller, Channing ; Markowski, Mark ; Carducci, Michael ; Eisenberger, Mario ; Beer, Tomasz (Tom) ; Song, Daniel Y. ; Deweese, Theodore L. ; Hearn, Jason W. ; Greco, Stephen ; Deville, Curtiland ; Desai, Neil B. ; Heath, Elisabeth I. ; Liauw, Stanley ; Spratt, Daniel E. ; Hung, Arthur ; Antonarakis, Emmanuel S. ; Tran, Phuoc T. / 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). In: BMC cancer. 2019 ; Vol. 19, No. 1.
@article{4e6bbb2306b6439bb50e6ee05f8bd19d,
title = "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)",
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)",
author = "Roche Kapoor and Deek, {Matthew P.} and Riley McIntyre and Natasha Raman and Megan Kummerlowe and Iyah Chen and Matt Gaver and Hao Wang and Sam Denmeade and Tamara Lotan and Channing Paller and Mark Markowski and Michael Carducci and Mario Eisenberger and Beer, {Tomasz (Tom)} and Song, {Daniel Y.} and Deweese, {Theodore L.} and Hearn, {Jason W.} and Stephen Greco and Curtiland Deville and Desai, {Neil B.} and Heath, {Elisabeth I.} and Stanley Liauw and Spratt, {Daniel E.} and Arthur Hung and Antonarakis, {Emmanuel S.} and Tran, {Phuoc T.}",
year = "2019",
month = "6",
day = "13",
doi = "10.1186/s12885-019-5805-z",
language = "English (US)",
volume = "19",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - 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)

AU - Kapoor, Roche

AU - Deek, Matthew P.

AU - McIntyre, Riley

AU - Raman, Natasha

AU - Kummerlowe, Megan

AU - Chen, Iyah

AU - Gaver, Matt

AU - Wang, Hao

AU - Denmeade, Sam

AU - Lotan, Tamara

AU - Paller, Channing

AU - Markowski, Mark

AU - Carducci, Michael

AU - Eisenberger, Mario

AU - Beer, Tomasz (Tom)

AU - Song, Daniel Y.

AU - Deweese, Theodore L.

AU - Hearn, Jason W.

AU - Greco, Stephen

AU - Deville, Curtiland

AU - Desai, Neil B.

AU - Heath, Elisabeth I.

AU - Liauw, Stanley

AU - Spratt, Daniel E.

AU - Hung, Arthur

AU - Antonarakis, Emmanuel S.

AU - Tran, Phuoc T.

PY - 2019/6/13

Y1 - 2019/6/13

N2 - 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.

AB - 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.

KW - Enzalutamide

KW - High-risk prostate cancer

KW - Prostatectomy

KW - Recurrent prostate cancer

KW - Salvage radiation therapy (SRT)

UR - http://www.scopus.com/inward/record.url?scp=85067287349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067287349&partnerID=8YFLogxK

U2 - 10.1186/s12885-019-5805-z

DO - 10.1186/s12885-019-5805-z

M3 - Article

C2 - 31196032

AN - SCOPUS:85067287349

VL - 19

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 572

ER -