Description:
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.
Title
- Brief Title: RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers
- Official Title: A Phase II Randomized Trial of RAdium-223 and SABR Versus SABR for oligomEtastatic Prostate caNcerS (RAVENS)
Clinical Trial IDs
- ORG STUDY ID:
J18147
- SECONDARY ID:
IRB00188450
- NCT ID:
NCT04037358
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Radium-223 | | Radium-223 and SABR |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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 | |
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.
| Maximum Eligible Age: | 100 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression-free survival |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Toxicity as assessed by number of participants who experience adverse events |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Number of participants who receive at least one fraction of SABR and Radium-223 who experience adverse events as defined by CTCAE v4.0 after first treatment of SABR and Radium-223. |
| Measure: | Local control at 12 months |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Time from starting treatment until local relapse is documented |
| Measure: | Time to locoregional progression |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Time from starting treatment until local and/or regional relapse is documented |
| Measure: | Time to distant progression |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Time from starting treatment until distant relapse is documented |
| Measure: | Time to new metastasis |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | ADT-free survival |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Time from randomization until initiation of androgen-deprivation therapy (ADT). |
| Measure: | Quality of Life as assessed by Pain Severity and Pain Interference using the Brief Pain Inventory |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Last Updated
May 7, 2021
