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.