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.

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy

“…Radiotherapy dose was not available for individual patients, but during that period doses of 60.0-70.0 Gy were commonly used at Johns Hopkins. 17…”

Should androgen deprivation therapy and other systemic treatments be used in men with prostate cancer and a rising PSA post-local treatments?

“…91 The ongoing randomised phase II SALV-ENZA trial is designed to assess the combination of salvage prostate bed RT (66.6-70.2 Gy) with 6 months of enzalutamide versus placebo in highrisk BCR patients (GS ⩾ 8 and either pT3 or positive margins). 92 Although it is important that this is a randomised trial, the standard arm omits ADT, which is a de-escalation compared to current standards, evoking the assumption that enzalutamide would sufficiently replace ADT. In addition, the trial includes only patients with PSA up to 0.7 ng/ml, which, based on previous evidence, likely excludes patients with higher PSA levels that are more likely to benefit from a combinatorial approach to RT, notably with ADT.…”