RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers

NCT ID: NCT04037358

Last Updated: 2025-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-09
• Study Completion Date: 2025-07-15

Brief 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. 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radium-223 and SABR

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

Group Type: EXPERIMENTAL

Radium-223

Intervention Type: DRUG

Radium-223 plus SABR will be within two weeks.

stereotactic ablative radiotherapy (SABR)

Intervention Type: RADIATION

SABR 1-5 fractions

SABR

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

Group Type: ACTIVE_COMPARATOR

stereotactic ablative radiotherapy (SABR)

Intervention Type: RADIATION

SABR 1-5 fractions

Interventions

Radium-223

Radium-223 plus SABR will be within two weeks.

Intervention Type: DRUG

stereotactic ablative radiotherapy (SABR)

SABR 1-5 fractions

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Congressionally Directed Medical Research Programs

FED

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ana Kiess, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins SKCCC

Locations

Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 40334149 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32487038 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00188450

Identifier Type: OTHER

Identifier Source: secondary_id

J18147

Identifier Type: -

Identifier Source: org_study_id