PRIMARY OBJECTIVES:
I. To assess the difference in fatigue 6 months after randomization in patients with mHSPC achieving optimal PSA response on intermittent relugolix + ARPI versus continuous relugolix/ADT + ARPI. (Cohort A)
II. To assess progression-free survival in patients with mHSPC on intermittent relugolix + ARPI at one year. (Cohort B)
SECONDARY OBJECTIVES:
I. To evaluate treatment effects on patient-reported outcomes (PROs). (Cohort A)
II. To determine if intermittent relugolix + ARPI will provide similar efficacy as continuous relugolix/ADT + ARPI in clinically relevant endpoints in participants with mHSPC who reached PSA ≤ 0.2 ng/mL after 6-12 months of relugolix + ARPI treatment. (Cohort A)
III. To assess the treatment-free interval at one year in patients achieving optimal PSA response. (Cohort B)
IV. To assess the change in quality of life measures from baseline. (Cohort B)
V. To evaluate the treatment efficacy of intermittent relugolix + ARPI. (Cohort B)
EXPLORATORY OBJECTIVES:
I. To evaluate the association of PROs with testosterone levels. (Cohort A)
II. To evaluate the effect of relugolix + ARPI on mHSPC. (Cohort A)
III. To evaluate the association of ecological momentary assessment (EMA) measures and PSA and testosterone levels. (Cohort A)
IV. To evaluate the association of ecological momentary assessment (EMA) measures and treatment status. (Cohort A)
V. To compare the safety between the experimental arm (intermittent ADT + ARPI) and control arm (continuous ADT + ARPI). (Cohort A)
VI. To analyze tumor-based biomarkers in tissue and blood to elucidate the biological mechanisms underlying differential PSA responses - specifically, achieving ≤ 0.2 ng/mL versus not. (Cohort A)
VII. To analyze association between blood-based biomarkers and cardiovascular and other health-related outcomes. (Cohort A)
VIII. To evaluate the association of PROs with testosterone. (Cohort B)
IX. To evaluate the safety of intermittent relugolix + ARPI on patients with mHSPC achieving PSA ≤ 0.2 ng/ml. (Cohort B)
X. To evaluate time to testosterone recovery based on prior duration of testosterone suppression. (Cohort B)
XI. To evaluate the association of ecological momentary assessment (EMA) measures and PSA and testosterone levels. (Cohort B)
XII. To evaluate the association of EMA measures and treatment reinitiation status (reinitiated versus [vs] not reinitiated). (Cohort B)
XIII. To analyze tumor-based biomarkers in tissue and blood to elucidate the biological mechanisms underlying differential PSA responses - specifically, achieving ≤ 0.2 ng/mL versus not. (Cohort B)
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT A:
STEP 1: Patients receive relugolix and an ARPI continuously for 6-12 months in the absence of disease progression or unacceptable toxicity.
STEP 2: After 6-12 months of treatment, patients with PSA ≤ 0.2 ng/mL are randomized to 1 of 2 arms.
ARM 1: Patients continue to receive standard of care continuous treatment with relugolix or ADT and ARPI per clinical investigator in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI and whole-body nuclear medicine bone scan throughout the study.
ARM 2: Patients receive intermittent treatment with relugolix and ARPI (treatment is interrupted when PSA ≤ 0.2 ng/ml and re-initiated if PSA is equal or higher than baseline, > 10 ng/ml, or at investigator's discretion) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI and whole-body nuclear medicine bone scan throughout the study.
COHORT B: Patients receive intermittent treatment with relugolix and ARPI (treatment is interrupted when PSA ≤ 0.2 ng/ml and re-initiated if PSA is equal or higher than baseline, > 10 ng/ml, or at investigator's discretion) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI and whole-body nuclear medicine bone scan throughout the study.
After completion of study treatment, patients are followed every 3 months for up to 3 years from the date of randomization for Cohort A and 3 years from the date of registration for Cohort B.
