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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00188450 | Other Identifier | JHM IRB |
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| Name | Class |
|---|---|
| Congressionally Directed Medical Research Programs | FED |
| Bayer | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Radium-223 and SABR | Experimental | First radium-223 infusion will be within two weeks of SABR |
|
| SABR | Active Comparator | SABR(1-5 fractions) will be administered for all men |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radium-223 | Drug | Radium-223 plus SABR will be within two weeks. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 24 months |
| Rate of Local Control at 12 Months |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Ana Kiess, M.D. | Johns Hopkins SKCCC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40334149 | Result | 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. | |
| 32487038 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Radium-223 and SABR | First radium-223 infusion will be within two weeks of SABR Radium-223: Radium-223 plus SABR will be within two weeks. stereotactic ablative radiotherapy (SABR): SABR 1-5 fractions |
| FG001 | SABR | SABR(1-5 fractions) will be administered for all men stereotactic ablative radiotherapy (SABR): SABR 1-5 fractions |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who completed the study
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| ID | Title | Description |
|---|---|---|
| BG000 | Radium-223 and SABR | First radium-223 infusion will be within two weeks of SABR Radium-223: Radium-223 plus SABR will be within two weeks. stereotactic ablative radiotherapy (SABR): SABR 1-5 fractions |
| BG001 | SABR |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Median | 95% Confidence Interval | Months | Up to 24 months |
|
From the time of enrollment to 1 year or until progression of disease (up to 2 years)
CTCAE (4.0) Grade 3 or higher adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Radium-223 and SABR | First radium-223 infusion will be within two weeks of SABR Radium-223: Radium-223 plus SABR will be within two weeks. stereotactic ablative radiotherapy (SABR): SABR 1-5 fractions |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
Treatment and follow-up occurred during the COVID-19 pandemic, leading to assessment biases associated with telemedicine encounters. This study was conducted before routine use of molecular imaging (not mandated) to corroborate disease burden detected on conventional imaging. The study size is small and limits the prognostic correlates observed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ana P. Kiess | Johns Hopkins University School of Medicine | 443-287-7528 | akiess1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 7, 2025 | Jul 24, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000615150 | Radium-223 |
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RAdium-223 and SABR Versus SABR (Stereotactic Ablative Radiotherapy)
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| stereotactic ablative radiotherapy (SABR) |
| Radiation |
SABR 1-5 fractions |
|
Percentage of participants achieving local control at 12 months |
| Up to 12 months |
| Time to Locoregional Progression | Time from starting treatment until local and/or regional relapse is documented | 12 months |
| Time to Distant Progression | Time from starting treatment until distant relapse is documented | Up to 24 months |
| 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. | Up to 24 months |
| 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. | Up to 24 months |
| 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. | Baseline, Day 360 |
| 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. | Baseline, Day 360 |
| 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. | 12 months |
| 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 | 12 Months |
| Derived |
| 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. |
SABR(1-5 fractions) will be administered for all men
stereotactic ablative radiotherapy (SABR): SABR 1-5 fractions
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| International Society of Urological Pathology (ISUP) Group Grade | ISUP grade group is a 5-tier system that categorizes the aggressiveness of prostate cancer. Grade Group 1 (lease aggressive) to Grade Group 5 (most aggressive). The ISUP group grade is based on corresponding Gleason scores. Grade group 1: (Gleason score <=6); Grade Group 2: (Gleason score 3+4 = 7); Grade Group 3: (Gleason score 4+3 = 7); Grade Group 4: (Gleason score 4+4 = 8. 3+5 = 8, or 5+3 = 8); Grade Group 5: (Gleason score 9 or 10) | Count of Participants | Participants |
|
| Initial Management/Treatment | Count of Participants | Participants |
|
| Previous Hormone Therapy | Count of Participants | Participants |
|
| Baseline PSA, ng/mL | Mean | Standard Deviation | ng/mL |
|
| Initial Imaging Type | Count of Participants | Participants |
|
| Initial Lesion | Count of Participants | Participants |
|
| Total Lesion Number | Count of Participants | Participants |
|
| Bone Lesions Number | Count of Participants | Participants |
|
| Bone Lesions Type | Count of Participants | Participants |
|
| Extra-pelvic lymph nodes | Count of Participants | Participants |
|
| OG001 | SABR | SABR(1-5 fractions) will be administered for all men stereotactic ablative radiotherapy (SABR): SABR 1-5 fractions |
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | Up to 24 months |
|
|
|
| Secondary | Rate of Local Control at 12 Months | Percentage of participants achieving local control at 12 months | One patient in the SABR arm never received imaging (data not collected) afterward due to loss of follow up/died for other reasons, so that patient will be censored out or excluded. | Posted | Mean | 95% Confidence Interval | percentage of participants | Up to 12 months |
|
|
|
| Secondary | Time to Locoregional Progression | Time from starting treatment until local and/or regional relapse is documented | There were no locoregional progression events at the site of SBRT during the time patients were on study. | Posted | 12 months |
|
|
| Secondary | Time to Distant Progression | Time from starting treatment until distant relapse is documented | Posted | Median | 95% Confidence Interval | Months | Up to 24 months |
|
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | Months | Up to 24 months |
|
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | Months | Up to 24 months |
|
|
|
| Secondary | 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. | Participants with missing data, and further 2 participants were not assessed due to disease progression for SBRT group and SBRT+Ra223 group, respectively. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, Day 360 |
|
|
|
| Secondary | 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. | Participants with missing data, and further 2 participants were not assessed due to disease progression for SBRT group and SBRT+Ra223 group, respectively. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, Day 360 |
|
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | Months | 12 months |
|
|
|
| Secondary | 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 | Posted | Median | 95% Confidence Interval | Months | 12 Months |
|
|
|
| 0 |
| 31 |
| 0 |
| 31 |
| 30 |
| 31 |
| EG001 | SABR | SABR(1-5 fractions) will be administered for all men stereotactic ablative radiotherapy (SABR): SABR 1-5 fractions | 0 | 33 | 0 | 33 | 33 | 33 |
| Anemia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Bloating | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Anal Hemorrhage | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Esophagitis | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Lymphocute cound decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Bruising | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment | Decreased appetite |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Erectile Dysfunction | Reproductive system and breast disorders | CTCAE (5.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment | Loose bowel Movements |
|
| Compression Fracture | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
|
| Neutrophl count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Urinary Urgency | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Any Adverse Event | General disorders | CTCAE (4.0) | Non-systematic Assessment | Number of patients whose worst AE was grade 1-2, 3 and total. |
|
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| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| Lymphocyte Count Decrease |
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| Insomnia |
|
| Musculoskeletal Pain |
|
| Day 360 BPI Score |
|
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