Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Conditions
Brief summary
The purpose of this study is to evaluate intermittent relugolix + androgen receptor pathway inhibitor (ARPI) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) achieving optimal PSA response.
Interventions
DRUGrelugolix + ARPI
Step 1: Continuous treatment with relugolix + ARPI
DRUGIntermittent- Relugolix or androgen deprivation therapy (ADT) + ARPI
Intermittent treatment with relugolix + ARPI.
DRUGrelugolix or androgen deprivation therapy (ADT) + ARPI
Step 2: Standard-of-care, continuous treatment with relugolix or androgen deprivation therapy (ADT) + ARPI.
DRUGrelugolix + ARPI.
Step 2: Intermittent treatment with relugolix + ARPI.
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cohort A Eligibility (Step 1 Registration) * Participant aged ≥ 18 years * Hormone-sensitive prostate cancer with histologically/cytologically confirmed adenocarcinoma without small cell histology. * Metastasis detected any time prior to study registration on conventional or functional imaging as determined by the treating investigator and can be of any site. * Baseline testosterone \>50 ng/dl before start of therapy for metastatic disease * PSA ≥ 1 ng/mL before start of therapy for metastatic disease * ECOG Performance Status ≤ 2 * Eligible to receive standard of care treatment with relugolix and APRI per clinical investigator. * Participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception requirements as described in Section 5.5.1. * If the risk of seminal transfer from the participant is present, the participant must agree to use a condom during sexual intercourse as described in Section 5.5.2. * Participants must agree not to donate sperm from the start of study therapy until 3 months after the last dose of study therapy. * Clinically significant adverse effects from any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy) must have resolved or have been determined to be clinically stable per the Investigator. * Has access to a smartphone and wireless services and is able to download and navigate study specific applications. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Cohort A Eligibility (Step 2 Registration) -PSA ≤ 0.2 ng/mL after 6-12 months of relugolix and androgen receptor pathway inhibitor treatment. Androgen receptor pathway inhibitor includes abiraterone, enzalutamide, apalutamide, darolutamide or similar drugs. Cohort B Eligibility * Participant aged ≥ 18 years * Hormone-sensitive prostate cancer with histologically/cytologically confirmed adenocarcinoma without small cell histology. * Metastasis detected any time prior to study registration on conventional or functional imaging as determined by clinical investigator and can be of any site. * PSA ≤ 0.2 ng/mL after treatment with androgen deprivation therapy or androgen receptor pathway inhibitor treatment or both of any duration. Androgen deprivation therapy in this context includes gonadotropin-releasing hormone agonists and antagonists. Androgen receptor pathway inhibitors include abiraterone, enzalutamide, apalutamide, darolutamide or similar drugs. * Eligible to receive standard of care treatment with relugolix and APRI per clinical investigator. * Participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception requirements as described in Section 5.5.1. * If the risk of seminal transfer from the participant is present, the participant must agree to use a condom during sexual intercourse as described in Section 5.5.2. * Participants must agree not to donate sperm from the start of study therapy until 3 months after the last dose of study therapy. * Has access to a smartphone and wireless services and is able to download and navigate study specific applications. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion criteria
Cohort A Eligibility (Step 1 Registration) * Participant received androgen deprivation therapy (defined as leuprolide or surgical castration) for metastatic hormone-sensitive prostate cancer. * The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study. * Known brain metastases or cranial epidural disease. --Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Participants must be neurologically stable and receiving a stable or decreasing corticosteroid dose at the time of study entry. * Current evidence of uncontrolled, significant intercurrent illness, infection, non-compliance or other safety concerns which may affect clinical trial participation. * Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study. * Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v5.0 Grade ≥ 3). * Participants taking prohibited medications as described in Section 6.6.2. Cohort A Eligibility (Step 2 Registration) * Receiving other systemic anti-cancer therapy for prostate cancer. Prior treatment before Step 2 registration is allowed. * Progression to metastatic castration-resistant prostate cancer per clinical investigator. * The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study. * Participants taking prohibited medications as described in Section 6.6.2. Cohort B Eligibility * Receiving other systemic anti-cancer therapy for prostate cancer. * History of surgical castration. * The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study. * Known brain metastases or cranial epidural disease. --Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Participants must be neurologically stable and receiving a stable or decreasing corticosteroid dose at the time of study entry * Current evidence of uncontrolled, significant intercurrent illness, infection, compliance or other safety concerns which may affect clinical trial participation. * Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study. * Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v5.0 Grade ≥ 3). * Participants taking prohibited medications as described in Section 6.6.1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: Brief Fatigue Inventory (BFI) score 6 months after randomization. | 6 months | 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. Scored from 0 (no Fatigue) to 10 (as bad as you can imagine), and 0 (Does not interfere) to 10 (Completely Interferes). |
| Cohort B: Progression-free survival (PFS) as defined as the time from intermittent study initiation (first treatment break) to the time of documented disease progression or death from any cause at one year. | 12 months | To assess PFS in patients with mHSPC on intermittent relugolix/ADT + ARPI at one year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in health-related quality of life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC-QLQC30). | 13 months | To evaluate treatment effects on patient-reported outcomes (PROs). EORTC-QLQC30 scored from 1 (not at all)- 4 (very much). |
| Changes in health-related quality of life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC-QLQ-PR25). | 13 months | To evaluate treatment effects on patient-reported outcomes (PROs). EORTC-QLQ-PR25 scored from 1 (not at all)- 4 (very much). |
| Sexual function improvement in those with intact sexual function at baseline as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire. | 13 months | To evaluate treatment effects on patient-reported outcomes (PROs). EORTC-QLQ-PR25, question 52-55.Scored from 1 (not at all)- 4 (very much). |
| Changes in severity of hot flashes as measured by the Hot Flash Related Daily Interference Scale (HFRDIS). | 13 months | To evaluate treatment effects on patient-reported outcomes (PROs). HFRDIS scored 0 (did not interfere to 10 (completely interfered). |
| Changes in cognitive function as measured by the PROMIS-Cognitive function Short Form 8a. | 13 months | To evaluate treatment effects on patient-reported outcomes (PROs). PROMIS-Cognitive function Short Form 8a scored 5 (Never)- 1 (very often- Several times a day). |
| Change from baseline over time in each PRO, including time to recovery and deterioration in the intermittent arm with treatment break and start. | 2 years | To evaluate treatment effects on patient-reported outcomes (PROs). |
| Time to metastatic castration-resistant prostate cancer. | 12 months | Cohort A: 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 B: To evaluate the treatment efficacy of intermittent relugolix/ADT + ARPI. |
| Overall survival and prostate cancer-specific survival at 3 years from the date of randomization. | 12 months | Cohort A: 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 B: Change from baseline over time in each PRO, including time to recovery and deterioration in intermittent arm with treatment break and start. |
| Time to systemic treatment change. | 12 months | 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 |
| Duration of time on treatment | 12 months | Cohort A: 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 B: To evaluate the treatment efficacy of intermittent relugolix/ADT + ARPI. |
| Time to first treatment restart | 12 months | Cohort A: 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 B: To evaluate the treatment efficacy of intermittent relugolix/ADT + ARPI. |
| Duration of time with testosterone < 50 ng/mL | 12 months | Cohort A: 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 B: To evaluate the treatment efficacy of intermittent relugolix/ADT + ARPI. |
| Testosterone-linked outcomes (time to recovery of testosterone ≥50 ng/dL; time to recovery of testosterone to baseline [≥screening testosterone level]). | 12 months | Cohort A: 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 B: To evaluate the treatment efficacy of intermittent relugolix/ADT + ARPI. |
| Duration of time to recovery of testosterone to normal range [>300 ng/dL]). | 12 months | Cohort A: 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 B: To evaluate the treatment efficacy of intermittent relugolix/ADT + ARPI. |
| The proportion of participants achieving a treatment-free interval (TFI) of at least one year from the time of registration and median TFI. | 12 months | To assess the TFI at one year in patients achieving optimal PSA response. |
| Change in Brief Fatigue Inventory (BFI) score from baseline to 6 months after registration. | 6 months | To assess the change in quality of life measures from baseline. BFI Scored from 0 (no Fatigue) to 10 (as bad as you can imagine), and 0 (Does not interfere) to 10 (Completely Interferes). |
| Changes in cognitive function as measured by the PROMIS-Cognitive Function Short Form 8a. | 13 months | To assess the change in quality of life measures from baseline. PROMIS-Cognitive function Short Form 8a scored 5 (Never)- 1 (very often- Several times a day). |
| Change from baseline over time in each PRO, including time to recovery and deterioration in intermittent arm with treatment break and start. | 13 months | To assess the change in quality of life measures from baseline. |
| Overall survival and prostate cancer specific survival at 3 years from the date of randomization. | 3 years | To evaluate the treatment efficacy of intermittent relugolix + ARPI. |
Countries
United States
Contacts
CONTACTErynn Peyton
CONTACTUmang Swami, MD
Outcome results
None listed