Radium-223 + SABR for Prostate Cancer

(RAVENS Trial)

Overseen By Phuoc Tran, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1-5 weeks

64 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase II non-blinded randomized study evaluating men with oligometastatic prostate cancer lesions randomized (1:1) to stereotactic ablative radiation therapy (SABR) versus SBAR + Radium-223. We are looking to determine the progression-free survival of men who have oligometastatic prostate cancer with at least one bone metastasis with stereotactic ablative radiation therapy (SABR) versus SABR + Radium-223.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are receiving abiraterone and prednisone or any other investigational agents.

What data supports the effectiveness of the treatment Radium-223 + SABR for Prostate Cancer?

Research shows that Stereotactic Ablative Radiotherapy (SABR) is promising for treating localized prostate cancer, with studies indicating it can improve quality of life and is well-tolerated. However, there is limited data on its long-term effectiveness and safety, especially for high-risk patients, and no specific data on the combination with Radium-223. ^{1 2 3 4 5}

Is the combination of Radium-223 and SABR generally safe for humans?

Stereotactic Ablative Radiotherapy (SABR) is generally well tolerated and has been shown to be safe in treating prostate cancer, with side effects similar to or lower than other radiation techniques. However, higher doses may increase genitourinary (related to the urinary system) and gastrointestinal (related to the digestive system) side effects. ^{4 5 6 7 8}

How is the Radium-223 + SABR treatment different from other prostate cancer treatments?

Radium-223 + SABR is unique because it combines a targeted alpha radiation therapy (Radium-223) that specifically attacks bone metastases with high-energy, short-range particles, with Stereotactic Ablative Radiotherapy (SABR), which delivers precise, high-dose radiation to tumors. This combination aims to maximize the radiation dose to both primary and metastatic prostate cancer, potentially improving disease control compared to standard treatments. ^{9 10 11 12 13}

Research Team

Ana Kiess, M.D.

Principal Investigator

Johns Hopkins SKCCC

Eligibility Criteria

Men over 18 with oligometastatic prostate cancer, treated primary tumor, PSA levels between 0.5-50, and at least one recent bone metastasis are eligible. They must have normal organ/marrow function and a life expectancy of over a year. Those with more than three years of ADT history or recent treatment aren't eligible.

Inclusion Criteria

PSA > 0.5 but <50

Testosterone > 125 ng/dL

My prostate cancer is progressing quickly.

Exclusion Criteria

My recent scans show more cancer spots than before.

I have suspected lung or liver cancer spread larger than 10 mm.

I am currently taking abiraterone and prednisone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic ablative radiation therapy (SABR) with or without Radium-223

1-5 weeks

1-5 visits (in-person)

Follow-up

Participants are monitored for progression-free survival and other outcomes

12 months

Regular visits (in-person and/or virtual)

Open-label extension (optional)

Participants may continue to receive treatment if beneficial

Long-term

Treatment Details

Interventions

• Radium-223
• Stereotactic Ablative Radiotherapy (SABR)

Trial Overview This Phase II trial compares the effectiveness of SABR alone versus SABR combined with Radium-223 in men with oligometastatic prostate cancer to see which is better for halting disease progression.

Participant Groups

Group I: Radium-223 and SABR Experimental Treatment 2 Interventions

First radium-223 infusion will be within two weeks of SABR

Group II: SABR Active Control 1 Intervention

SABR(1-5 fractions) will be administered for all men

Stereotactic Ablative Radiotherapy (SABR) is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as SABR/SBRT for:

• Low-risk prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Approved in United States as SABR/SBRT for:

• Low-risk prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer
• Recurrent prostate cancer

Approved in United Kingdom as SABR/SBRT for:

• Low-risk prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Department of Defense Congressionally Directed Medical Research Program

Collaborator

Trials

3

Recruited

640+

Findings from Research

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 152 men with intermediate risk prostate cancer, weekly stereotactic ablative radiotherapy (SABR) resulted in better short-term bowel and urinary quality of life compared to every other day treatment, but there were no significant differences in late toxicity or long-term quality of life outcomes after 62 months.

Both treatment regimens showed similar rates of biochemical failure and overall survival, indicating that while weekly SABR may reduce acute side effects, it does not compromise long-term efficacy or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT). Alayed, Y., Quon, H., Ong, A., et al.[2021]

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 radiotherapy (SABR) has been shown to be feasible and well tolerated for low- and intermediate-risk prostate cancer patients, with promising results from large randomized studies comparing it to conventional treatments.

While SABR shows potential benefits and cost-effectiveness, there is currently insufficient data to recommend its use for high-risk prostate cancer patients outside of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer. Loblaw, A.[2021]

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]

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]

Stereotactic body radiotherapy (SBRT) is shown to be safe and effective for treating node-positive prostate cancer, with a median follow-up of 30 months revealing no severe gastrointestinal toxicities and manageable genitourinary side effects.

In a study of 60 patients, SBRT resulted in a 3-year overall survival rate of 89% and a biochemical failure-free survival rate of 77%, indicating promising long-term outcomes even in patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. Telkhade, T., Murthy, V., Kanala, TS., et al.[2021]

Stereotactic ablative body radiation (SABR) is a promising non-invasive treatment for localized prostate cancer, showing similar efficacy to brachytherapy in terms of disease control and lower side effects, making it a potentially safer option.

SABR is also more cost-effective and resource-efficient compared to traditional radiation techniques, but further well-powered studies are needed to confirm its benefits before it can be considered standard care, especially for patients with metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy in patients with prostate cancer. Loblaw, A., Liu, S., Cheung, P.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

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

2. Ireland pubmed.ncbi.nlm.nih.gov

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT). [2021]

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

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer. [2021]

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

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. [2021]

8. China pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy in patients with prostate cancer. [2023]

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

Toxicity and Efficacy of Concurrent Androgen Deprivation Therapy, Pelvic Radiotherapy, and Radium-223 in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer. [2022]

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

Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland: A real-world evidence multicenter study. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Impact of DNA damage repair defects on response to radium-223 and overall survival in metastatic castration-resistant prostate cancer. [2021]

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

Nursing management of patients with castration-resistant prostate cancer undergoing radium-223 dichloride treatment. [2018]

13. Japan pubmed.ncbi.nlm.nih.gov

Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer. [2018]