This phase II trial compares the usual treatment of radiation therapy alone to using the study drug, relugolix, plus the usual radiation therapy in patients with castration-sensitive prostate cancer that has spread to limited other parts of the body (oligometastatic). Relugolix is in a class of medications called gonadotropin-releasing hormone (GnRH) receptor antagonists. It works by decreasing the amount of testosterone (a male hormone) produced by the body. It may stop the growth of cancer cells that need testosterone to grow. Radiation therapy uses high-energy x rays or protons to kill tumor cells. The addition of relugolix to the radiation may reduce the chance of oligometastatic prostate cancer spreading further.
PRIMARY OBJECTIVE: I. Compare conventional radiological progression-free survival (rPFS) for positron emission tomography (PET)-detected, biochemically recurrent, oligometastatic, castration-sensitive prostate cancer patients treated with stereotactic ablative body radiation therapy (SABR) plus placebo versus (vs.) SABR plus relugolix. SECONDARY OBJECTIVES: I. Compare conventional or PET-based radiological progression-free survival (prPFS) between treatment arms. II. Compare patient-reported sexual and hormonal quality of life as assessed by corresponding Expanded Prostate Cancer Index Composite Short Form (EPIC-26) domains between treatment arms. III. Compare other measures of quality of life obtained from the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ5D-5L), European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue instruments between the two treatment arms. IV. Compare time to salvage therapy and time to castration-resistance between treatment arms. V. Compare local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival between treatment arms. VI. Determine adverse events rates and compare rates between the two treatment arms. EXPLORATORY OBJECTIVE: I. Evaluate genomic and peripheral tissue and blood markers of treatment response. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive placebo orally (PO) once daily (QD) on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, computed tomography (CT), magnetic resonance imaging (MRI), prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 9 and 12 months, subsequently every 6 months to month 60, and then annually thereafter or at the time of progression.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
194
Undergo urine and blood sample collection
Undergo bone scan
Undergo CT and/or PET/CT
Given fluciclovine F18
Undergo MRI and/or PET/MRI
Given PO
Undergo PET/CT and/or PET/MRI
Undergo PSMA PET/CT or PET/MRI
Given PO
Undergo SABR
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
RECRUITINGAlta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
RECRUITINGTower Cancer Research Foundation
Beverly Hills, California, United States
RECRUITINGMarin General Hospital
Greenbrae, California, United States
Radiological progression-free survival (rPFS)
The rPFS curves will be estimated by the Kaplan-Meier method and compared between the two treatment arms using a one-sided, logrank test stratified by the three randomization factors.
Time frame: Time from randomization to the occurrence of radiological progression detected by conventional imaging or death from any cause, assessed up to 5 years
Positron emission tomography (PET)-based radiological progression-free survival
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.
Time frame: Time from randomization to the occurrence of conventional or PET-based radiological progression or death from any cause, assessed up to 5 years
Metastasis-free survival
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.
Time frame: From randomization to distant metastases or death from any cause, assessed up to 5 years
Overall survival
Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.
Time frame: From randomization to death from any cause, assessed up to 5 years
Sexual and hormonal quality of life
Assessed by Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
Time frame: Up to 5 years from randomization
Quality of life
Assessed by European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ5D-5L) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-30).
Time frame: Up to 5 years from randomization
Fatigue
Assessed by Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue short form.
Time frame: Up to 5 years from randomization
Time from randomization to administration of salvage therapy
Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and sub-distribution hazard ratios (SHRs) will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time frame: Up to 5 years from randomization
Time from randomization to castrate-resistant prostate cancer
Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time frame: Up to 5 years from randomization
Time from randomization to local progression within a stereotactic ablative body radiation therapy (SABR)-targeted lesion
Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time frame: Up to 5 years from randomization
Time from randomization to biochemical progression
Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time frame: Up to 5 years from randomization
Time from randomization to the occurrence of distance metastases
Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time frame: Up to 5 years from randomization
Time from randomization to death from prostate cancer
Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time frame: Up to 5 years from randomization
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UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
RECRUITINGLos Angeles General Medical Center
Los Angeles, California, United States
ACTIVE_NOT_RECRUITINGUSC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
ACTIVE_NOT_RECRUITINGCedars Sinai Medical Center
Los Angeles, California, United States
RECRUITINGMemorial Medical Center
Modesto, California, United States
RECRUITINGUC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
ACTIVE_NOT_RECRUITING...and 229 more locations