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

NCT06378866 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: MC230502R01CA28612723-012176R01CA300454
• Study Type: interventional
• Target: 532
• Locations: 1 country
• Sites: 3

Brief 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 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.

Conditions

Recurrent Castration-Sensitive Prostate Carcinoma; Recurrent Prostate Cancer; Castration-resistant Prostate Cancer; Biochemically Recurrent Prostate Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 5 years

Secondary Outcomes (2)

• Overall survival (OS)

  Up to 5 years

• Biochemcial progression-free survival (bPFS)

  Up to 5 years

Study Arms (4)

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.

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.

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.

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.

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

Interventions

Abiraterone DRUG

Given abiraterone

Also known as: Abiraterone acetate, CB-7598, CB7598, Zytiga

Group A (SBRT, APRI, ADT)

Apalutamide DRUG

Given apalutamide

Also known as: ARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927

Group A (SBRT, APRI, ADT)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting); Group C (sXRT, watchful waiting); Group D (initial observation, image-guided therapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting); Group C (sXRT, watchful waiting); Group D (initial observation, image-guided therapy)

Computed Tomography PROCEDURE

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

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting); Group C (sXRT, watchful waiting); Group D (initial observation, image-guided therapy)

Darolutamide DRUG

Given darolutamide

Also known as: Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788, Nubeqa, ODM 201, ODM-201

Group A (SBRT, APRI, ADT)

Degarelix DRUG

Given degarelix

Also known as: ASP3550, FE200486, Firmagon

Group A (SBRT, APRI, ADT)

Enzalutamide DRUG

Given enzalutamide

Also known as: ASP9785, MDV3100, Xtandi

Group A (SBRT, APRI, ADT)

Goserelin DRUG

Given goserelin

Also known as: ICI-118630

Group A (SBRT, APRI, ADT)

Histrelin DRUG

Given histrelin

Group A (SBRT, APRI, ADT)

Leuprolide DRUG

Given leuprolide

Also known as: Leuprorelin

Group A (SBRT, APRI, ADT)

Magnetic Resonance Imaging PROCEDURE

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

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting); Group C (sXRT, watchful waiting); Group D (initial observation, image-guided therapy)

Patient Observation OTHER

Undergo watchful waiting or initial observation

Also known as: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting); Group C (sXRT, watchful waiting); Group D (initial observation, image-guided therapy)

Positron Emission Tomography PROCEDURE

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

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting); Group C (sXRT, watchful waiting); Group D (initial observation, image-guided therapy)

Prednisone DRUG

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

Group A (SBRT, APRI, ADT)

Questionnaire Administration OTHER

Ancillary studies

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting); Group C (sXRT, watchful waiting); Group D (initial observation, image-guided therapy)

Relugolix DRUG

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

Group A (SBRT, APRI, ADT)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation (SABR), Stereotactic Ablative Body Radiation Therapy

Group A (SBRT, APRI, ADT); Group B (SBRT, watchful waiting)

Triptorelin DRUG

Given triptorelin

Also known as: 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, AY25650, CL-118,532, CL118532, Detryptoreline

Group A (SBRT, APRI, ADT)

Radiation Therapy RADIATION

Undergo sXRT

Also known as: Cancer Radiotherapy, Irradiation, RADIATION, Radiotherapeutics, RADIOTHERAPY

Group B (SBRT, watchful waiting)

Image-Guided Therapy PROCEDURE

Undergo image-guided therapy

Also known as: Image Guided Therapy

Group D (initial observation, image-guided therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• BRIO (Gropus C \& D only):
• Prostate-specific antigen (PSA) between 0.2 and 1.5 ng/mL with PSA above 0.2 on at least two consecutive measurements at least 5 days apart
• No local or metastatic recurrence apparent on advanced molecular imaging
• Serum testosterone \> 100 ng/dL
• 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) and aspartate transaminase (AST) ≤ 3 x upper limit of normal (ULN) ( ≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)

You may not qualify if:

• 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:
• Surgery ≤ 3 weeks prior to registration
• Chemotherapy for prostate cancer at any time
• Androgen receptor pathway inhibitor 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

abiraterone; Abiraterone Acetate; apalutamide; Specimen Handling; darolutamide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; enzalutamide; Goserelin; histrelin; Leuprolide; Magnetic Resonance Spectroscopy; X-Rays; Watchful Waiting; Observation; Prednisone; deltacortene; prednylidene; relugolix; Radiosurgery; Triptorelin Pamoate; Radiotherapy; Radiation; Radiotherapy, Image-Guided

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Spectrum Analysis; Chemistry Techniques, Analytical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation, Ionizing; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Pregnadienediols; Pregnadienes; Pregnanes; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative

Study Officials

• Jacob J. Orme, MD, PhD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Cancer Center Clinical Trials

CONTACT

507-293-6386

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 23, 2024
• Study Start: June 3, 2024
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): February 28, 2031
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (3)