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Prostate CancerPhase 2RAVENSNCT04037358

RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers

A Phase 2 study testing Radium-223 and stereotactic ablative radiotherapy (SABR) in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 100 years, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Radium-223 and stereotactic ablative radiotherapy (SABR)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
1 siteUnited States
Study dates
9 Aug 2019to 15 Jul 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone or soft tissue (with at least one bone metastasis) develop within the past 6-months that are ≤ 5.0 cm or <250 cm3
  • Patient must have had their primary tumor treated with surgery and/or radiation.
  • Histologic confirmation of malignancy (primary or metastatic tumor).
  • PSADT <15 months. PSA doubling time (PSADT) will be calculated using as many PSA values that are available from time of relapse (PSA > 0.2). To calculate PSADT, the Memorial Sloan Kettering Cancer Center Prostate Cancer Prediction Tool will be used. It can be found at the following web site: https://www.mskcc.org/nomograms/prostate/psa-doubling-time.
  • Patient may have had prior systemic therapy and/or ADT associated with treatment of their primary prostate cancer. Patient may have had ADT associated with salvage radiation therapy (to the primary prostate cancer or pelvis is allowed).
  • PSA > 0.5 but <50.
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  • Testosterone > 125 ng/dL.
  • Patient must be ≥ 18 years of age.
  • Patient must have a life expectancy ≥ 12 months.
  • Patient must have an ECOG performance status ≤ 2.
  • Patient must have normal organ and marrow function as defined as:
  • Before the first administration of Xofigo, the absolute neutrophil count (ANC) should be ≥ 1.5 x 109/L, the platelet count ≥ 100 x 109/L and hemoglobin ≥ 10 g/dL.
  • Patient must have the ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • No more than 3 years of ADT is allowed, with the most recent ADT treatment having occurred greater than 6 months prior to enrollment.
  • PSMA-PET/MRI or PSMA-PET/CT scan within the past 6 months with results that demonstrate more disease lesions than baseline CT/Bone Scan
  • Castration-resistant prostate cancer (CRPC).
  • Spinal cord compression or impending spinal cord compression.
  • Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis).
  • Patient receiving any other investigational agents.
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  • Patient receiving abiraterone and prednisone.
  • Patient is participating in a concurrent treatment protocol.
  • Serum creatinine > 3 times the upper limit of normal.
  • Total bilirubin > 3 times the upper limit of normal.
  • Liver Transaminases > 5-times the upper limit of normal.
  • Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.
  • Prior salvage treatment to the primary prostate cancer or pelvis is allowed.
  • Refusal to sign informed consent.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Johns Hopkins

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: A Phase II Randomized Trial of RAdium-223 and SABR Versus SABR for oligomEtastatic Prostate caNcerS (RAVENS)

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.

Read the detailed description

The metastatic capacity of prostate cancer (PCa) behaves along a spectrum of disease that contains an oligometastatic state where metastases are limited in number and location. The importance of local consolidation of all tumor deposits in oligometastatic disease to forestall further metastatic dissemination is now backed by small randomized studies. Our previous Baltimore ORIOLE randomized trial of stereotactic ablative radiation (SABR) alone, highly focused, high-dose radiation, versus observation in oligometastatic PCa final data demonstrate a progression-free survival (PFS) benefit of SABR alone. The patterns of failure from our ORIOLE trial in combination with prior data suggest one dominant mode of failure is from microscopic disease particularly those with bone-tropic biology. These are important early clinical data suggesting the existence of an oligometastatic state and the importance of local therapies in the management of these patients. Radiopharmaceutical therapy (RPT) approaches have not been applied in the oligometastatic space and thus the opportunity to target micrometastatic disease in conjunction with local consolidation of macroscopic disease with SABR has the potential to provide a curative paradigm for patients with oligometastatic PCa. We introduce the successor trial to ORIOLE called RAVENS that is a phase II randomized trial of SABR +/- the bone metastasis seeking RPT Xofigo in men with oligometastatic PCa. We hypothesize macroscopic prostate tumors support the growth of and help nurture future distant metastases and this process can be impacted most by total, macro- and microscopic, tumor consolidation. In addition, we hypothesize that circulating biomarkers can identify men with oligometastasis that benefit the most from SABR and RPT.

Conditions
Prostate Cancer
Being tested
Radium-223, stereotactic ablative radiotherapy (SABR)
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Radium-223Drug

    Radium-223 plus SABR will be within two weeks.

  • stereotactic ablative radiotherapy (SABR)Radiation

    SABR 1-5 fractions

Study groups in NCT04037358
Study groupRoleWhat they receive
Radium-223 and SABRExperimentalFirst radium-223 infusion will be within two weeks of SABR
Receives: Drug: Radium-223; Radiation: stereotactic ablative radiotherapy (SABR)
SABRActive comparatorSABR(1-5 fractions) will be administered for all men
Receives: Radiation: stereotactic ablative radiotherapy (SABR)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival

    Time to progression in men who have oligometastatic prostate cancer after therapy. Progression is defined by PCWG2 criteria as follows: >=25% increase in PSA from nadir (and by >=2ng/mL), and/or clinical/radiographic progression (clinical progression = symptomatic progression, worsening of disease-related symptoms or new cancer-related complications; radiographic progression on CT scan defined by RECIST 1.1 criteria: >=20% enlargement in sum diameter of soft-tissue target lesions; or on bone scan >=1 new bone lesions), initiation of ADT or death due to any cause, whichever occurs first.

    Measured: Up to 24 months

Secondary outcomes (10)
  1. Toxicity as Assessed by Number of Participants Who Experience Adverse Events Grade 3 or Greater (CTCAE v4.0)

    Adverse events grade 3 or higher (defined by CTCAE v4.0) measured as treatment related events in either SABR or SABR and Radium-223 arms.

    Measured: Up to 24 months

  2. Rate of Local Control at 12 Months

    Percentage of participants achieving local control at 12 months

    Measured: Up to 12 months

  3. Time to Locoregional Progression

    Time from starting treatment until local and/or regional relapse is documented

    Measured: 12 months

  4. Time to Distant Progression

    Time from starting treatment until distant relapse is documented

    Measured: Up to 24 months

  5. Metastasis-Free Survival

    Time from treatment start to the time of a newly documented tumor metastasis by CT and/or bone scan. Subjects who do not progress will be censored at the time of the last contact.

    Measured: Up to 24 months

  6. Androgen-deprivation Therapy (ADT)-Free Survival

    Time from randomization until initiation of androgen-deprivation therapy (ADT). ADT Free Survival (ADT-FS) is defined as the time from starting treatment to the time of initiation of palliative ADT.

    Measured: Up to 24 months

  7. Quality of Life as Assessed by Pain Severity and Pain Interference Score With Imputations Using the Brief Pain Inventory

    The brief pain inventory assesses the severity of pain, location of pain, amount of pain over the last 24 hours, and impact of pain on daily functions. Scores for the 4 pain severity items and 7 pain interference items range from 0-10, where 10 is the worst pain or pain that completely interferes with described activity and 0 is the least pain or does not interfere with described activity. The mean of these scores is used to measure pain severity and pain interference.

    Measured: Baseline, Day 360

  8. Change in Quality of Life as Assessed by Pain Severity and Pain Interference With Imputations Using the Brief Pain Inventory

    The brief pain inventory assesses the severity of pain, location of pain, amount of pain over the last 24 hours, and impact of pain on daily functions. Scores for the 4 pain severity items and 7 pain interference items range from 0-10, where 10 is the worst pain or pain that completely interferes with described activity and 0 is the least pain or does not interfere with described activity. The mean of these scores is used to measure pain severity and pain interference.

    Measured: Baseline, Day 360

  9. Time to New Metastatsis

    Time to New Metastasis (TNM) is defined as the time from starting treatment to the time of a new documented tumor metastasis by CT and/or bone scan. Subjects who do not progress will be censored at the time of the last contact.

    Measured: 12 months

  10. Duration of Response

    Response will be defined as evidence of CR, PR, or stable disease. The duration of response will be measured from the start of treatment until the criteria for progression are met

    Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2019
  2. Study start9 Aug 2019
  3. Primary completion15 Jul 2025
  4. Study completion15 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
RAdium-223 and SABR Versus SABR (Stereotactic Ablative Radiotherapy)
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04037358
Sponsor's protocol ID
J18147
Other IDs
IRB00188450
Acronym
RAVENS
Status last verified
Dec 2025
First submitted
26 Jul 2019
Last updated
19 Dec 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wang JH, Sherry AD, Bazyar S, Sutera P, Radwan N, Phillips RM, Deek MP, Lu J, Dipasquale S, Deville C, DeWeese TL, Song DY, Wang H, Hobbs RF, Malek R, Dudley SA, Greco SC, Antonarakis ES, Marshall CH, Denmeade S, Paller CJ, Carducci MA, Pienta KJ, Oz OK, Ramotar M, Leenstra JL, Park SS, Abramowitz MC, Desai N, Berlin A, Stish BJ, Tang C, Tran PT, Kiess AP. Outcomes of Radium-223 and Stereotactic Ablative Radiotherapy Versus Stereotactic Ablative Radiotherapy for Oligometastatic Prostate Cancers: The RAVENS Phase II Randomized Trial. J Clin Oncol. 2025 Jun 20;43(18):2059-2068. doi: 10.1200/JCO-25-00131. Epub 2025 May 7.

    PubMed 40334149
  • Hasan H, Deek MP, Phillips R, Hobbs RF, Malek R, Radwan N, Kiess AP, Dipasquale S, Huang J, Caldwell T, Leitzel J, Wendler D, Wang H, Thompson E, Powell J, Dudley S, Deville C, Greco SC, Song DY, DeWeese TL, Gorin MA, Rowe SP, Denmeade S, Markowski M, Antonarakis ES, Carducci MA, Eisenberger MA, Pomper MG, Pienta KJ, Paller CJ, Tran PT. A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS). BMC Cancer. 2020 Jun 1;20(1):492. doi: 10.1186/s12885-020-07000-2.

    PubMed 32487038

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radium-223 and stereotactic ablative radiotherapy (SABR) in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04037358, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.

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