Recurrent Castration-Sensitive Prostate CarcinomaPhase 2DIVINENCT06378866
Stereotactic Body Radiation Therapy Plus Immediate or Delayed Androgen Receptor Pathway Inhibitor and Androgen Deprivation Therapy or Salvage Radiation Therapy for the Treatment of Prostate Cancer, DIVINE Trial
A Phase 2 study testing Abiraterone, Apalutamide and Biospecimen Collection in people with Recurrent Castration-Sensitive Prostate Carcinoma and Recurrent Prostate Cancer, run by Mayo Clinic at 3 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Recurrent Castration-Sensitive Prostate Carcinoma, Recurrent Prostate Cancer, Castration-resistant Prostate Cancer
- What is being tested?
- Abiraterone, Apalutamide and Biospecimen Collection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 532 participants
- Where
- 3 sitesUnited States
- Study dates
- 3 Jun 2024to 28 Feb 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Disease characteristics:
- DEVIATE (Groups A and B only):
- Clinical confirmation of metachronous (metastatic) recurrent hormone-sensitive prostate cancer
- Five (5) or fewer metastases with at least one metastasis beyond the pelvis on advanced molecular and/or conventional imaging
- Serum testosterone > 100ng/dL or clinically deemed non-castrate
Show all 21Show fewer
- BRIO (Groups C \& D only):
- Prostate-specific antigen (PSA) between 0.15 and 1.5 ng/mL with PSA ≥ 0.15 ng/mL on at least two measurements at least 5 days apart
- No local or metastatic recurrence apparent on advanced molecular imaging
- Serum testosterone > 100 ng/dL or clinically deemed non-castrate
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
- Hemoglobin ≥ 8.0 g/dL (obtained ≤ 15 days prior to registration)
- Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 15 days prior to registration)
- Platelet count ≥ 80,000/mm^3 (obtained ≤ 15 days prior to registration)
- Alanine aminotransferase (ALT) or aspartate transaminase (AST) ≤ 3 x upper limit of normal (ULN) (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
- Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula (obtained ≤ 15 days prior to registration)
- Provide written informed consent
- Ability to complete questionnaire(s) by themselves or with assistance
- Willingness to provide mandatory blood specimens for correlative research
- Willingness to allow access to provide tissue specimens for correlative research
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Who cannot join
- 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
- Pregnant persons
- Nursing persons
- Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception
- Prior metastasis-directed therapy
- Any of the following prior therapies:
Show all 28Show fewer
- Surgery ≤ 3 weeks prior to registration
- Chemotherapy for prostate cancer at any time
- Androgen receptor pathway inhibitors such as abiraterone, apalutamide, darolutamide, or enzalutamide in the last 2 years
- Uncontrolled intercurrent non-cardiac illness including, but not limited to:
- Ongoing or active infection
- Psychiatric illness/social situations
- Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
- Any other conditions that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for prostate cancer.
- Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- Other active malignancy ≤ 3 years prior to registration
- EXCEPTIONS: Curatively treated non-melanotic skin cancer or papillary thyroid cancer
- NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment such as chemotherapy or antihormonal therapy for their cancer
- History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Cancer Center Clinical Trials contact
United States3 sites, 3 recruiting
- Recruiting
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Cancer Center Clinical Trials, 507-293-6386
- Recruiting
Mayo Clinic in Arizona
Phoenix, Arizona, 85054
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Cancer Center Clinical Trials, 507-293-6386
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Cancer Center Clinical Trials, 507-293-6386
About this study
Official title: MC230502 Dynamic Investigator Initiated Enterprise (DIVINE) in Prostate Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- 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.
- Conditions
- Recurrent Castration-Sensitive Prostate Carcinoma, Recurrent Prostate Cancer, Castration-resistant Prostate Cancer, Biochemically Recurrent Prostate Carcinoma
- Being tested
- Abiraterone, Apalutamide, Biospecimen Collection, Bone Scan, Computed Tomography
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbirateroneDrug
Also called Abiraterone acetate, CB-7598, CB7598, Zytiga
Given abiraterone
ApalutamideDrug
Also called ARN 509, ARN-509, ARN509, Erleada
Given apalutamide
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone ScanProcedure or surgery
Also called Bone Scintigraphy
Undergo bone scan
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography (CAT), Computerized Axial Tomography
Undergo CT
DarolutamideDrug
Also called Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788
Given darolutamide
DegarelixDrug
Also called ASP3550, FE200486, Firmagon
Given degarelix
EnzalutamideDrug
Also called ASP9785, MDV3100, Xtandi
Given enzalutamide
GoserelinDrug
Also called ICI-118630
Given goserelin
HistrelinDrug
Given histrelin
LeuprolideDrug
Also called Leuprorelin
Given leuprolide
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Patient ObservationOther
Also called Active Surveillance, deferred therapy, expectant management, Observation
Undergo watchful waiting or initial observation
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography (PET)
Undergo PET
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given prednisone
Questionnaire AdministrationOther
Ancillary studies
RelugolixDrug
Also called 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
Given relugolix
Stereotactic Body Radiation TherapyRadiation
Also called SABR, SBRT, Stereotactic Ablative Body Radiation (SABR), Stereotactic Ablative Body Radiation Therapy
Undergo SBRT
TriptorelinDrug
Also called 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, AY25650
Given triptorelin
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiation, RADIATION, Radiotherapeutics
Undergo sXRT
Image-Guided TherapyProcedure or surgery
Also called Image Guided Therapy
Undergo image-guided therapy
| Study group | Role | What they receive |
|---|---|---|
| Group A (SBRT, APRI, ADT) | Active comparator | 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. Receives: 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 |
| Group B (SBRT, watchful waiting) | Experimental | 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. Receives: 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 |
| Group C (sXRT, watchful waiting) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Patient Observation; Procedure: Positron Emission Tomography; Other: Questionnaire Administration |
| Group D (initial observation, image-guided therapy) | Active comparator | 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 5 years
Secondary outcomes (2)
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.
Measured: 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.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2024
- Study start3 Jun 2024
- Primary completion28 Feb 2031 (estimated)
- Study completion28 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Castration-Sensitive Prostate CarcinomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 532 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jacob J. Orme, MD, PhD, Principal investigator, Mayo Clinic in Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06378866
- Sponsor's protocol ID
- MC230502
- Other IDs
- R01CA286127, 23-012176, R01CA300454
- Acronym
- DIVINE
- Status last verified
- Jul 2026
- First submitted
- 16 Apr 2024
- Last updated
- 20 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wei N, Phillips RM, Kwon E, Stish BJ, Ehman EC, Lucien F, O'Byrne J, Bobek O, Shi Q, Andrews JR, Boorjian SA, Park SS, Orme JJ, Sharma V. Biochemical Recurrence Irradiation or Observation (BRIO) in patients with prostate cancer: protocol for a randomised control trial. BJU Int. 2026 Sep;138(3):403-408. doi: 10.1111/bju.70305. Epub 2026 May 12.
PubMed 42117295