PRIMARY OBJECTIVE:
I. To determine whether 12 months of androgen deprivation therapy (ADT) and darolutamide
improves metastasis-free survival (MFS) compared to 12 months of ADT plus placebo in men
with high risk prostate cancer (defined by Cancer of the Prostate Risk Assessment
Post-surgical [CAPRA-S] score >= 3 and a high Decipher score (>= 0.6) [C3+D+]) who have
undergone radical prostatectomy.
SECONDARY OBJECTIVES:
I. To determine whether 12 months of ADT and darolutamide improves recurrence-free
survival (RFS) compared to 12 months of ADT plus placebo in men with high-risk prostate
cancer that have undergone radical prostatectomy.
II. To determine whether 12 months of ADT and darolutamide improves event-free survival
(EFS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer
that have undergone radical prostatectomy.
III. To determine whether 12 months of ADT and darolutamide improves overall survival
(OS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that
have undergone radical prostatectomy.
IV. To determine the rate of testosterone recovery and time to testosterone recovery in
each treatment arm.
V. To evaluate the safety and tolerability of ADT and darolutamide.
CORRELATIVE OBJECTIVES FOR EXPLORATORY BIOMARKERS:
I. To discover a novel gene expression signature in the Decipher transcriptome platforms
that is predictive of clinical outcome, as defined by the primary and secondary
objectives of this study, in response to ADT by intensification with darolutamide versus
ADT alone.
II. To assess the prevalence of subclasses of established transcriptome expression
signatures and prospectively validate their predictive value for ADT response, these
include: (i) androgen (AR) activity (ii) Basal-luminal subtyping based on modified PAM50,
and (iii) ADT score.
III. To assess whether the spectrum of high Decipher scores (0.6-1.0), prostate-specific
antigen (PSA) levels at presentation and post-radical prostatectomy (RP) and final
pathology variables affect the response and outcome to ADT and darolutamide.
QUALITY OF LIFE (QOL) OBJECTIVES:
I. To compare overall quality of life, measured by Functional Assessment of Cancer
Therapy-Prostate (FACT-P) total score, at 18 months between the two arms. (Primary) II.
To compare the change in overall quality of life, measured by FACT-P total score, from
baseline to 18 months between the two arms. (Secondary) III. To compare patient-reported
fatigue (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scores) at 12
months between the two treatment arms. (Secondary) IV. To compare the change in
subjective patient-reported cognitive function (FACT-Cognitive [Cog]) from baseline to 12
months between the treatment arms. (Exploratory) V. To compare subjective
patient-reported cognitive function (FACT-Cog scores) at 12 months between the two
treatment arms. (Exploratory)
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via
injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3
injections), or every month for 12 months (12 injections) in the absence of disease
progression or unacceptable toxicity. Patients also receive a placebo four times daily
(QID) for 52 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via
injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3
injections), or every month for 12 months (12 injections) in the absence of disease
progression or unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks
in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 36
months.