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

Status

Recruiting

Phase

Phase 2

Enrollment

532 participants (estimated)

Sponsor

Mayo Clinic · Other

Design

Randomized · Open label (no masking)

Countries

1 country

United States

Start

3 Jun 2024

Primary completion

28 Feb 2031 (estimated)

Completion

28 Feb 2031 (estimated)

First posted

23 Apr 2024

Last update posted

20 Jul 2026

Conditions

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

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.

• Active comparator

  Group A (SBRT, APRI, ADT)

  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.

• Experimental

  Group B (SBRT, watchful waiting)

  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.

• Experimental

  Group C (sXRT, watchful waiting)

  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.

• Active comparator

  Group D (initial observation, image-guided therapy)

  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.

1. Modified radiographic progression-free survival (mrPFS) (Groups A & B)

   Time frame · Up to 5 years

   Registry description

   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.

2. Distant progression-free survival (PFS) (Groups C & D)

   Time frame · Up to 5 years

   Registry description

   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.

No study cites this trial.