Radiation and Hormone Therapy for Prostate Cancer

(DIVINE Trial)

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Androgen deprivation

Must not be taking: Chemotherapy, Androgen inhibitors

Disqualifiers: Pregnancy, Active infection, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 months

220 Participants Needed

Trial Summary

What is the purpose of this trial?

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). 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. Giving SBRT alone with watchful waiting may be as effective in treating prostate cancer as giving SBRT together with ARPI and ADT.

Do I need to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have been on androgen receptor pathway inhibitors in the last 2 years, you may not be eligible to participate.

What data supports the effectiveness of the treatment Stereotactic Ablative Radiotherapy (SABR) for prostate cancer?

Research shows that SABR, especially using the CyberKnife system, is promising for treating prostate cancer, including cases that are intermediate- to very-high-risk. It has been found to potentially improve survival and delay further spread in patients with certain types of prostate cancer. ^{1 2 3 4 5}

Is the combination of radiation and hormone therapy for prostate cancer safe?

Research on stereotactic ablative radiotherapy (SABR) using CyberKnife for prostate cancer shows it is generally safe, with very few severe side effects reported. Some patients experienced mild to moderate gastrointestinal (stomach and intestines) and genitourinary (urinary and reproductive organs) reactions, but serious long-term effects were rare. ^{1 4 6 7 8}

How is the treatment Stereotactic Body Radiation Therapy (SBRT) unique for prostate cancer?

Stereotactic Body Radiation Therapy (SBRT), also known as Stereotactic Ablative Radiotherapy (SABR), is unique because it uses the CyberKnife system to deliver highly precise radiation to prostate cancer, even in cases with advanced or oligometastatic disease. This method allows for targeted treatment with fewer sessions compared to traditional radiation, potentially improving survival and reducing the risk of further cancer spread. ^{1 2 5 9 10}

Research Team

Jacob Orme

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for men with hormone-sensitive prostate cancer that has spread and returned after improving. Participants should not have allergies to the treatments used in the study, which include various medications and radiation therapy.

Inclusion Criteria

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)

I have up to 5 cancer spread sites, with at least one outside my pelvis.

Willingness to provide mandatory blood specimens for correlative research

Exclusion Criteria

I have received chemotherapy for prostate cancer.

I had surgery less than 3 weeks ago.

Pregnant persons

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo SBRT and receive ARPI and ADT for up to 6 months, with cycles repeating every 4 months

6 months

Regular visits for treatment and monitoring

Watchful Waiting

Patients are monitored for disease progression after treatment

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up every 6 months

Treatment Details

Interventions

• Abiraterone
• Goserelin
• Stereotactic Body Radiation Therapy

Trial Overview The DIVINE Trial is testing how well stereotactic body radiation therapy (SBRT) works alone or when combined with ARPIs and ADT in treating metastatic, recurrent prostate cancer. It compares different treatment timings to see which is more effective.

Participant Groups

Group I: Group B (SBRT, watchful waiting) Experimental Treatment 8 Interventions

Patients undergo SBRT with watchful waiting. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity.

Group II: Group A (SBRT, APRI, ADT) Active Control 19 Interventions

Patients undergo SBRT and receive APRI (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.

Stereotactic Body Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Approved in European Union as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Approved in Canada as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

In a study of 87 men with oligometastatic prostate cancer treated with stereotactic ablative radiotherapy (SABR), the median disease-free survival (DMFS) was 21.8 months for hormone-sensitive patients, indicating a significant benefit from this treatment.

Combining SABR with short-term androgen-deprivation therapy improved both biochemical progression-free survival (bPFS) and DMFS in patients with oligorecurrent hormone-sensitive prostate cancer, suggesting a potential strategy for enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer. Mercier, C., Claessens, M., De Troyer, B., et al.[2022]

In a study comparing two different fractionation schedules of stereotactic ablative radiotherapy (SABR) for prostate cancer, the 2-fraction treatment (26 Gy/2) showed significantly better quality of life (QOL) outcomes in the bowel domain compared to the 5-fraction treatment (40 Gy/5), with a lower rate of clinically important changes in bowel function.

Both treatment groups had low five-year biochemical failure rates (3.3% for 2-fraction and 4.6% for 5-fraction), indicating that the 2-fraction SABR is not only effective but also well tolerated, warranting further randomized trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials. Alayed, Y., Quon, H., Cheung, P., et al.[2020]

Stereotactic ablative radiation (SAbR) at a dose of 45 Gy in 5 fractions shows a promising safety profile for treating localized prostate cancer, with acute urinary and gastrointestinal toxicity rates of 20.4% and 7.3%, respectively, and low rates of late toxicity after 2 years.

The treatment demonstrated excellent efficacy, with a biochemical failure-free survival rate of 100% at 1 year and 98.7% at 2 years, indicating strong disease control outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. Chen, L., Gannavarapu, BS., Desai, NB., et al.[2022]

A single session of stereotactic ablative body radiotherapy (SABR) for oligometastatic prostate cancer was found to be feasible and safe, with only one significant adverse event (a vertebral fracture) reported among 33 patients over a 2-year follow-up period.

The treatment resulted in high local progression-free survival rates of 97% at 1 year and 93% at 2 years, with nearly half of the patients (48%) avoiding the need for androgen deprivation therapy at the 2-year mark, indicating effective disease control and maintained quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. Siva, S., Bressel, M., Murphy, DG., et al.[2022]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is a safe and effective treatment for low and intermediate risk prostate cancer, with only a 2.25% failure rate observed in a study of 400 patients over a median follow-up of 15 months.

The treatment resulted in a significant decline in prostate-specific antigen (PSA) levels, with no severe late adverse effects reported, indicating that SABR could be considered for more advanced cases of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyberknife Radioablation of Prostate Cancer – Preliminary Results for 400 Patients Miszczyk, L., Namysł Kaletka, A., Napieralska, A., et al.[2020]

Stereotactic body radiation therapy (SBRT) using CyberKnife for localized prostate cancer was found to be safe, with no severe treatment-related toxicities (grade 3 or higher) reported among 44 patients over a median follow-up of 40 months.

The treatment showed excellent efficacy, with a 100% cause-specific survival rate and progression-free survival rate, and a high biochemical failure-free rate of 90.8% for high-risk patients, particularly with the 34 Gy in 4 fractions regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided stereotactic body radiation therapy for localized prostate cancer. Kang, JK., Cho, CK., Choi, CW., et al.[2022]

In a study of 84 low-risk prostate cancer patients treated with Stereotactic Ablative Body Radiotherapy (SABR), long-term quality of life (QOL) outcomes were generally positive, with a median follow-up of 50.8 months, although some patients reported declines in urinary (17.9%), bowel (26.2%), and sexual (37.5%) QOL domains.

Dosimetric factors such as rectal D1cc and penile bulb V35 were identified as significant predictors of worse QOL, highlighting the importance of adhering to strict dosimetric constraints to minimize side effects from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. Elias, E., Helou, J., Zhang, L., et al.[2018]

In a study of 26 men with low- to intermediate-risk prostate cancer treated with CyberKnife SBRT, there was a significant reduction in PSA levels, indicating an effective biochemical response to the therapy.

Despite a decrease in testosterone levels post-treatment, there was no increase in biochemical hypogonadism one year after therapy, suggesting that CyberKnife SBRT is well-tolerated and does not significantly impact hormonal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer. Oermann, EK., Suy, S., Hanscom, HN., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. [2017]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

7. Thailand pubmed.ncbi.nlm.nih.gov

Cyberknife Radioablation of Prostate Cancer – Preliminary Results for 400 Patients [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Image-guided stereotactic body radiation therapy for localized prostate cancer. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer. [2022]