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

Must not be taking: Abiraterone, Prednisone, Investigational agents

Disqualifiers: Castration-resistant prostate cancer, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1-5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for men with oligometastatic prostate cancer, a type of cancer that has spread to a few locations, particularly in the bones. Researchers compare the effects of stereotactic ablative radiation therapy (SABR) alone to SABR combined with a radioactive drug called Radium-223 (also known as Xofigo or Radium Ra-223 dichloride). The goal is to determine which treatment helps patients live longer without cancer progression. Suitable candidates have had their primary prostate tumor treated, have up to three asymptomatic bone or soft tissue metastases that appeared in the last six months, and show no signs of more advanced disease. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Radium-223 is generally well-tolerated by patients with prostate cancer. Studies have found that when combined with stereotactic ablative radiation therapy (SABR), Radium-223 does not seem to slow the disease's progression, making the combination manageable for patients.

Radium-223 specifically targets cancer that has spread to the bones, a common occurrence in prostate cancer. It works by disrupting harmful interactions between cancer cells and bone, helping to protect nearby healthy tissues.

Most patients experience mild side effects, such as nausea, diarrhea, and low blood cell counts, especially when also receiving chemotherapy. Serious side effects are less common.

Overall, current evidence suggests that the combination of Radium-223 and SABR is safe for humans, with side effects that are usually mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Radium-223 with Stereotactic Ablative Radiotherapy (SABR) for prostate cancer because it offers a unique approach. Most treatments for prostate cancer, like hormone therapy and chemotherapy, focus on systemic effects. However, Radium-223 specifically targets bone metastases by delivering radiation directly to areas where cancer has spread in the bones, which is common in advanced prostate cancer. Meanwhile, SABR provides highly focused radiation to the tumor site itself, minimizing damage to surrounding tissues. This dual approach could potentially enhance treatment effectiveness while reducing side effects, making it a promising option for patients.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will compare the combination of Radium-223 and Stereotactic Ablative Radiotherapy (SABR) with SABR alone for men with oligometastatic prostate cancer, where the cancer has spread to only a few locations. Studies have shown that combining Radium-223 with SABR can prolong the period before the cancer worsens. Radium-223 targets and kills cancer cells in the bones, a common site for prostate cancer spread. Researchers are testing this combination because early evidence suggests it might control cancer spread more effectively than SABR alone. ^{1 3 4 6 7}

Who Is on the Research Team?

Ana Kiess, M.D.

Principal Investigator

Johns Hopkins SKCCC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12169860/

Outcomes of Radium-223 and Stereotactic Ablative ... Outcomes of radium-223 and stereotactic ablative radiotherapy versus stereotactic ablative radiotherapy for oligometastatic prostate cancers.

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-25-00131?af=R

Outcomes of Radium-223 and Stereotactic Ablative ... Randomized clinical trials (RCTs) have shown progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) without androgen ...

3. urotoday.com urotoday.com/conference-highlights/astro-2024/astro-2024-prostate-cancer/155251-astro-2024-initial-results-of-a-phase-2-trial-of-stereotactic-body-radiation-therapy-hormone-androgen-deprivation-therapy-and-radium-223-dichloride-for-oligometastatic-castrate-sensitive-prostate-cancer-sharp.html

ASTRO 2024: Initial Results of a Phase 2 Trial ... The SHARP trial (NCT03361735) aims to investigate the synergy between SBRT and radiopharmaceuticals (Radium-223) in treating oligometastatic prostate cancer, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40334149/

Outcomes of Radium-223 and Stereotactic Ablative ... - PubMed Adding Ra223 to SABR MDT in BM omCSPC does not delay progression of disease. We provide evidence for an HiRi mutational signature and TCR ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07000-2

A phase II randomized trial of RAdium-223 dichloride and ... The RAVENS trial will be the first described phase II, non-blinded, randomized study to compare SABR +/− radium-223 dichloride in patients with HSOPCa and 3 or ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04037358/

Clinical Trial: NCT04037358 This is a Phase II non-blinded randomized study evaluating men with oligometastatic prostate cancer lesions randomized (1:1) to stereotactic ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825002070

A new era for radium-223? Optimizing treatment by ... Radium-223 dichloride is a calcium-mimetic agent that targets bone lesions, disrupting the vicious circle between tumor cells and the bone microenvironment, and ...