A Phase II Randomized, Decentralized, De-escalation Study in Patients With Metastatic Hormone-Sensitive Prostate Cancer Achieving Optimal PSA Response (OPTIMAS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 2
- 主要终点
- Cohort A: Brief Fatigue Inventory (BFI) score 6 months after randomization.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
- •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.
- •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.
- •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.
排除标准
- •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.
- •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.
- •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.
研究组 & 干预措施
Cohort B
Participants who have achieved PSA ≤ 0.2 ng/mL are eligible and will receive intermittent treatment with relugolix + ARPI.
干预措施: Intermittent- Relugolix or androgen deprivation therapy (ADT) + ARPI (Drug)
Cohort A: Arm 1
INDUCTION (Step 1): Participants will receive continuous treatment with relugolix + an androgen receptor pathway inhibitor (ARPI).
After 6-12 months of continuous treatment, participants whose PSA is ≤ 0.2 ng/mL and who have completed step two registration will be randomized to one of two treatment arms:
• Cohort A: Arm 1 will continue standard-of-care, continuous treatment with relugolix or androgen deprivation therapy (ADT) + ARPI per clinical investigator.
干预措施: relugolix + ARPI (Drug)
Cohort A: Arm 1
INDUCTION (Step 1): Participants will receive continuous treatment with relugolix + an androgen receptor pathway inhibitor (ARPI).
After 6-12 months of continuous treatment, participants whose PSA is ≤ 0.2 ng/mL and who have completed step two registration will be randomized to one of two treatment arms:
• Cohort A: Arm 1 will continue standard-of-care, continuous treatment with relugolix or androgen deprivation therapy (ADT) + ARPI per clinical investigator.
干预措施: relugolix or androgen deprivation therapy (ADT) + ARPI (Drug)
Cohort A: Arm 2
INDUCTION (Step 1): Participants will receive continuous treatment with relugolix + an androgen receptor pathway inhibitor (ARPI).
After 6-12 months of continuous treatment, participants whose PSA is ≤ 0.2 ng/mL and who have completed step two registration will be randomized to one of two treatment arms:
• Cohort A: Arm 2 will receive intermittent treatment with relugolix + ARPI.
干预措施: relugolix + ARPI (Drug)
Cohort A: Arm 2
INDUCTION (Step 1): Participants will receive continuous treatment with relugolix + an androgen receptor pathway inhibitor (ARPI).
After 6-12 months of continuous treatment, participants whose PSA is ≤ 0.2 ng/mL and who have completed step two registration will be randomized to one of two treatment arms:
• Cohort A: Arm 2 will receive intermittent treatment with relugolix + ARPI.
干预措施: relugolix + ARPI. (Drug)
结局指标
主要结局
Cohort A: Brief Fatigue Inventory (BFI) score 6 months after randomization.
时间窗: 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.
时间窗: 12 months
To assess PFS in patients with mHSPC on intermittent relugolix/ADT + ARPI at one year.
次要结局
- 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)
- 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)
- 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)
- Duration of time on treatment(12 months)
- Changes in severity of hot flashes as measured by the Hot Flash Related Daily Interference Scale (HFRDIS).(13 months)
- Changes in cognitive function as measured by the PROMIS-Cognitive function Short Form 8a.(13 months)
- 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)
- Time to metastatic castration-resistant prostate cancer.(12 months)
- Overall survival and prostate cancer-specific survival at 3 years from the date of randomization.(12 months)
- Time to systemic treatment change.(12 months)
- Time to first treatment restart(12 months)
- Duration of time with testosterone < 50 ng/mL(12 months)
- Duration of time to recovery of testosterone to normal range [>300 ng/dL]).(12 months)
- Testosterone-linked outcomes (time to recovery of testosterone ≥50 ng/dL; time to recovery of testosterone to baseline [≥screening testosterone level]).(12 months)
- 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)
- Change in Brief Fatigue Inventory (BFI) score from baseline to 6 months after registration.(6 months)
- Changes in cognitive function as measured by the PROMIS-Cognitive Function Short Form 8a.(13 months)
- Change from baseline over time in each PRO, including time to recovery and deterioration in intermittent arm with treatment break and start.(13 months)
- Overall survival and prostate cancer specific survival at 3 years from the date of randomization.(3 years)