A Phase 2 interventional study of Abiraterone and Apalutamide in Recurrent Castration-Sensitive Prostate Carcinoma, Recurrent Prostate Cancer and Castration-resistant Prostate Cancer, sponsored by Mayo Clinic. Recruiting at 3 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-20.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
This phase II trial studies the effects of stereotactic body radiation therapy (SBRT) and the timing of treatment with androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) in treating patients with hormone sensitive prostate cancer that has spread from where it first started to other places in the body (metastatic), and that has come back after a period of improvement (recurrent). It also studies the effects of salvage radiation therapy (sXRT) on prostate cancer and to see if radiation to the pelvis helps prevent prostate cancer from spreading elsewhere. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Androgen can cause the growth of prostate cells. ADT lowers the amount of androgen made by the body. This may help stop the growth of tumor cells that need androgen to grow. Androgen receptor pathway inhibitors work by blocking the effects of androgen to stop the growth and spread of tumor cells. sXRT is a targeted radiation treatment for the prostate, typically given when cancer possibly returns after surgery or radiation. Its goal is to destroy any tumor cells in the area. Giving SBRT alone with watchful waiting may be as effective in treating prostate cancer as giving SBRT together with ARPI and ADT and sXRT may be effective in treating prostate cancer and preventing it from spreading elsewhere.
PRIMARY OBJECTIVES:
I. To evaluate and compare modified radiographic progression-free survival (mrPFS) in patients with metachronous recurrent oligometastatic prostate cancer treated with SBRT and 6 months ADT/ARPI followed by watchful wait (Group A) versus SBRT followed by watchful waiting (Group B). (De-escalation stratified by Extracellular Vesicles--Irradiation with Antiandrogen Therapy Exclusion [DEVIATE]) II. To evaluate and compare distant progression-free survival (PFS), landmarked at 12 months, in patients with biochemically recurrent prostate cancer treated with sXRT followed by watchful waiting (Group C) versus initial observation and subsequent image-guided therapy (Group D). (Biochemical Recurrence Irradiation versus Observation [BRIO])
SECONDARY OBJECTIVES:
I. To evaluate and compare overall survival (OS) between treatment groups. II. To evaluate and compare biochemical progression-free survival (bPFS) between treatment groups.
III. To evaluate and compare distant progression-free survival (PFS) starting from study registration, in patients with biochemically recurrent prostate cancer treated with sXRT followed by watchful waiting (Group C) versus initial observation and subsequent image-guided therapy (Group D).
TERTIARY OBJECTIVES:
I. To estimate rates of salvage radiotherapy to the pelvis in patients with biochemically recurrent prostate cancer treated with initial observation and subsequent image-guided therapy (Group D).
II. To evaluate the adverse event profile of the study treatments as assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
III. To evaluate and compare castration-resistant prostate cancer (CRPC)-free survival between treatment groups NOTE: CRPC-free survival: radiographic progression-free survival with castrate-level testosterone (\< 50ng/mL).
IV. Determine the efficacy of extracellular vesicles (EVs) as a minimal residual disease (MRD) marker.
V. Determine the efficacy of EVs as an early indicator of disease relapse. VI. Determine whether early ADT and ARPI hasten CRPC. VII. Determine how circulating tumor deoxyribonucleic acid (ctDNA) compares as a biomarker to EVs.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
DEVIATE COHORT: Patients are randomized to 1 of 2 groups.
GROUP A: Patients undergo SBRT and receive ARPI (abiraterone and prednisone, apalutamide, darolutamide, or enzalutamide) and ADT (leuprolide, triptorelin, histrelin, goserelin, degarelix, or relugolix). Cycles repeat every 4 months (16 weeks) for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients then undergo watchful waiting thereafter until disease progression.
GROUP B: Patients undergo SBRT with watchful waiting. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity.
BRIO COHORT: Patients are randomized to 1 of 2 groups.
GROUP C: Patients undergo sXRT with watchful waiting. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity.
GROUP D: Patients undergo initial observation with subsequent image-guided therapy based on visualized distant progression, which may consist of cross-over to groups A \& B, other off-trial radiotherapy, systemic therapy, surgical intervention, or other intervention per clinician discretion. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo blood sample collection and positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), or bone scan throughout the trial.
Upon completion of study interventions patients are followed up every 6 months for up to 5 years.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's planned enrollment of 532 is above the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.
Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.
Counted across the registry records on this site, refreshed daily.
Disease characteristics:
DEVIATE (Groups A and B only):
BRIO (Groups C \& D only):
Exclusion Criteria:
Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown
Any of the following prior therapies:
Uncontrolled intercurrent non-cardiac illness including, but not limited to:
Uncontrolled intercurrent illness including, but not limited to:
Other active malignancy ≤ 3 years prior to registration
Patients undergo SBRT and receive ARPI (abiraterone and prednisone, apalutamide, darolutamide, or enzalutamide) and ADT (leuprolide, triptorelin, histrelin, goserelin, degarelix, or relugolix). Cycles repeat every 4 months (16 weeks) for up to 6 months in the absence of unacceptable toxicity. Patients then undergo watchful waiting thereafter until disease progression. Additionally, patients undergo blood sample collection and PET, CT, MRI, or bone scan throughout the trial.
Drug: Abiraterone · Drug: Apalutamide · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Drug: Darolutamide · Drug: Degarelix · Drug: Enzalutamide · Drug: Goserelin · Drug: Histrelin · Drug: Leuprolide · Procedure: Magnetic Resonance Imaging · Other: Patient Observation · Procedure: Positron Emission Tomography · Drug: Prednisone · Other: Questionnaire Administration · Drug: Relugolix · Radiation: Stereotactic Body Radiation Therapy · Drug: Triptorelin
Patients undergo SBRT with watchful waiting. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET, CT, MRI, or bone scan throughout the trial.
Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Other: Patient Observation · Procedure: Positron Emission Tomography · Other: Questionnaire Administration · Radiation: Stereotactic Body Radiation Therapy · Radiation: Radiation Therapy
Patients undergo sXRT with watchful waiting. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET, CT, MRI, or bone scan throughout the trial.
Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Other: Patient Observation · Procedure: Positron Emission Tomography · Other: Questionnaire Administration
Patients undergo initial observation with subsequent image-guided therapy based on visualized distant progression, which may consist of cross-over to groups A \& B, other off-trial radiotherapy, systemic therapy, surgical intervention, or other intervention per clinician discretion. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET, CT, MRI, or bone scan throughout the trial.
Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Other: Patient Observation · Procedure: Positron Emission Tomography · Other: Questionnaire Administration · Procedure: Image-Guided Therapy
Given abiraterone
Also known as: Abiraterone acetate, CB-7598, CB7598, Zytiga
Given apalutamide
Also known as: ARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo bone scan
Also known as: Bone Scintigraphy
Undergo CT
Also known as: CAT, CAT Scan, Computed Axial Tomography (CAT), Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Given darolutamide
Also known as: Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788, Nubeqa, ODM 201, ODM-201
Given degarelix
Also known as: ASP3550, FE200486, Firmagon
Given enzalutamide
Also known as: ASP9785, MDV3100, Xtandi
Given goserelin
Also known as: ICI-118630
Given histrelin
Given leuprolide
Also known as: Leuprorelin
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, Nuclear Magnetic Resonance (NMR) Imaging, NMRI, Nuclear Magnetic Resonance Imaging (NMRI), sMRI, Structural MRI (sMRI), NMR Imaging
Undergo watchful waiting or initial observation
Also known as: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting
Undergo PET
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography (PET), Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
Given prednisone
Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone
Ancillary studies
Given relugolix
Also known as: N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, Relumina, TAK 385, TAK-385
Undergo SBRT
Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation (SABR), Stereotactic Ablative Body Radiation Therapy
Given triptorelin
Also known as: 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, AY25650, CL-118,532, CL118532, Detryptoreline
Undergo sXRT
Also known as: Cancer Radiotherapy, Irradiation, RADIATION, Radiotherapeutics, RADIOTHERAPY
Undergo image-guided therapy
Also known as: Image Guided Therapy
Modified radiographic progression-free survival (mrPFS) (Groups A & B)
Modified radiographic progression-free survival (mrPFS) is defined as the time from the date of randomization (enrollment to study) to the date of the first occurrence of the following events: death due to all causes or radiographic progression per Prostate Cancer Working Group 3 Criteria, which is not addressable by stereotactic body radiation therapy (SBRT). Radiographic progression not addressable by SBRT per the treating physician NOTE: Radiographic progression disease that can be addressed by SBRT will not be an mrPFS event. NOTE: Event-free patients will be censored at their last imaging assessment.
Time frame: Up to 5 years
Distant progression-free survival (PFS) (Groups C & D)
Defined as the date from the date of randomization + 1 year to the date of the first occurrence of death due to all causes or distant progression. Local progression will NOT be considered a distant progression event. Event-free patients will be censored at their last imaging assessment or prostate-specific antigen evaluation, whichever is later.
Time frame: Up to 5 years
Overall survival (OS)
Defined as time from randomization (enrolled to study) to the date of death due to any cause. Will be conducted on modified intent-to-treat (mITT) and per-protocol (PP) populations whenever it is applicable and plausible. Safety-related analyses will be performed on the safety population.
Time frame: Up to 5 years
Biochemcial progression-free survival (bPFS)
Defined as the time from randomization (enrollment to study) up to the date of death due to any cause or biochemical progressive disease, whichever occurs first. Will be conducted on mITT and PP populations whenever it is applicable and plausible. Safety-related analyses will be performed on the safety population.
Time frame: Up to 5 years
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Mayo Clinic