Trials / Recruiting

RecruitingNCT06378866

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

MC230502 Dynamic Investigator Initiated Enterprise (DIVINE) in Prostate Cancer

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 532 (estimated)

Sponsor: Mayo Clinic · Academic / Other
Sex: Male
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

Interventions

Type	Name	Description
DRUG	Abiraterone	Given abiraterone
DRUG	Apalutamide	Given apalutamide
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Scan	Undergo bone scan
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Darolutamide	Given darolutamide
DRUG	Degarelix	Given degarelix
DRUG	Enzalutamide	Given enzalutamide
DRUG	Goserelin	Given goserelin
DRUG	Histrelin	Given histrelin
DRUG	Leuprolide	Given leuprolide
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Patient Observation	Undergo watchful waiting or initial observation
PROCEDURE	Positron Emission Tomography	Undergo PET
DRUG	Prednisone	Given prednisone
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Relugolix	Given relugolix
RADIATION	Stereotactic Body Radiation Therapy	Undergo SBRT
DRUG	Triptorelin	Given triptorelin
RADIATION	Radiation Therapy	Undergo sXRT
PROCEDURE	Image-Guided Therapy	Undergo image-guided therapy

Timeline

Start date: 2024-06-03
Primary completion: 2029-05-31
Completion: 2029-05-31
First posted: 2024-04-23
Last updated: 2025-12-26

Locations

3 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06378866. Inclusion in this directory is not an endorsement.