Clinical trial NCT04037358: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Department of Defense Congressionally Directed Medical Research Program
name: Bayer
First posted: 2019-07-30
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RAdium-223 and SABR Versus SABR (Stereotactic Ablative Radiotherapy)
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 12 months
Secondary outcomes:
measure: Toxicity as assessed by number of participants who experience adverse events
timeFrame: 12 months
measure: Local control at 12 months
timeFrame: 12 months
measure: Time to locoregional progression
timeFrame: 12 months
measure: Time to distant progression
timeFrame: 12 months
measure: Time to new metastasis
timeFrame: 12 months
measure: ADT-free survival
timeFrame: 12 months
measure: Quality of Life as assessed by Pain Severity and Pain Interference using the Brief Pain Inventory
timeFrame: 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
Study officials:
affiliation: Johns Hopkins SKCCC
name: Ana Kiess, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.