A Study of Stereotactic Body Radiation Therapy and Radium (Ra-223) Dichloride in Prostate Cancer That Has Spread to the Bones

Study Overview
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Brief Summary
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Participants will either receive treatment with standard SBRT and the study drug Radium (Ra-223) dichloride, or standard SBRT alone.

Official Title
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SAXON-PC: A Phase II Randomized Trial of Stereotactic Body Radiation Therapy (SBRT) And Radium (Ra-223) Dichloride for Oligorecurrent, Non-castrate Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Radium dichloride
* Diagnostic Test: PET Scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven prostate adenocarcinoma ≥ 18 years old Primary prostate tumor must have been treated with prior prostatectomy or definitive radiotherapy Men with prior salvage radiotherapy to the prostate bed and/or locoregional lymph nodes are eligible assuming normalization of testosterone Negative multi-parametric MRI and/or negative biopsy of the prostate (or prostate bed) within 60 days of enrollment Pre-enrollment imaging (any bone imaging modality per institutional standard of care) demonstrates oligometastatic disease with 1-3 discrete metastatic lesions of the bone performed within 60 days of study enrollment; screening PSMA PET confirming 1-3 sites of oligometastatic disease performed within 60 days of enrollment. All bony oligometastatic sites must be deemed appropriate to receive 3 fraction SBRT to a dose of 9 Gy x 3 at best judgment of treating radiation oncologist Prostate specific antigen (PSA) ≥ 0.5 ng/mL but ≤ 50 ng/mL Patients may have had prior androgen deprivation therapy (ADT) but must have normal testosterone levels (>100 ng/dL) at time of enrollment; patients with baseline low testosterone but no ADT exposure are eligible Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Subjects who have not had surgical removal of their prostate and have a partner of child bearing potential must agree to use condoms beginning at the signing of the consent until at least 6 months after the last dose of study drug. Because of the potential side effect on spermatogenesis associated with radiation, female partners of childbearing potential must agree to use a highly effective contraceptive method during and for 6 months after completing treatment. Examples of highly effective contraception options for women include implantable uterine devices (hormonal or non-hormonal), oral, patch and parenteral contraceptives (when taken as prescribed). Adequate hematological, liver and renal function Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 10.0 g/dL Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN Creatinine ≤ 1.5 x ULN with normal creatinine clearance Albumin > 25 g/L Patient willing and able to comply with the protocol, including follow-up visits and examination Exclusion Criteria: Pathological findings consistent with small cell and/or neuroendocrine carcinoma of the prostate or any other histology Any metastatic site >5 cm in maximum diameter Patients with documented castration resistant prostate cancer (CRPC) Patients with any form of conventional, metabolic or molecular imaging (including PET imaging with PSMA, fluciclovine and/or FDG tracers) within 60 days of enrollment that demonstrate more than 3 discrete metastatic lesions Patients with evidence of nonpelvic lymph nodal or any visceral metastases Patients with evidence of progressing locoregional lymph nodes (prior lymphadenectomy or definitive/salvage RT to the pelvic lymph nodes is acceptable assuming no evidence of progression) Patients with documented or suspected impending significant spinal cord compression defined as epidural spinal cord compression (ESCC) grade 2 or higher using the Bilsky scale Patients with parenchymal brain metastases Patient received any other investigational therapeutic agents or other anticancer therapeutics within 4 weeks prior to randomization Major surgery within 30 days prior to start of study drug Any prior systemic therapy with radionuclide agents (e.g., strontium-89, samarium-153, rhenium-186, rhenium-188 or Radium (Ra-223) dichloride) for the treatment of bony metastases Fecal incontinence History of another malignancy within the previous 3 years except for the following: adequately treated basal cell or squamous cell skin cancer Any other serious illness or medical condition, such as but not limited to: Any infection greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 5.0 Grade 2 New York Heart Association (NYHA) Class III or IV heart failure Crohn's disease or ulcerative colitis Bone marrow dysplasia or myelodysplastic syndrome

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Participants will receive two cycles of Radium (Ra-223) dichloride at 55 kBq/kg or 0.00149 mCi/kg or 1.49 uCi/kg every 4 weeks followed 2-3 weeks later by SBRT at a dose of 9 Gy per fraction for 3 fractions (total dose of 27 Gy) to all sites of radiographically apparent metastatic disease. | Drug: Radium dichloride<br>* Two cycles of Radium (Ra-223) dichloride at 55 kBq/kg or 0.00149 mCi/kg or 1.49 uCi/kg every 4 weeks followed 2-3 weeks later by SBRT at a dose of 9 Gy per fraction for 3 fractions (total dose of 27 Gy) to all sites of radiographically apparent metastatic disease. SBRT fractions can be administered every day or every other day per institutional practice. An additional 4 cycles of Radium (Ra-223) dichloride at 55 kBq/kg or 0.00149 mCi/kg or 1.49 uCi/kg every 4 weeks will then be administered, resuming 2-3 weeks after completion of the final fraction of SBRT.<br>* Other names: Ra-223;|
| Active Comparator: Control Arm:<br>Participants will receive SBRT at a dose of 9 Gy per fraction for 3 fractions (total dose of 27 Gy) to all sites of radiographically apparent metastatic disease. SBRT fractions can be administered every day or every other day per institutional practice. | Drug: Radium dichloride<br>* Two cycles of Radium (Ra-223) dichloride at 55 kBq/kg or 0.00149 mCi/kg or 1.49 uCi/kg every 4 weeks followed 2-3 weeks later by SBRT at a dose of 9 Gy per fraction for 3 fractions (total dose of 27 Gy) to all sites of radiographically apparent metastatic disease. SBRT fractions can be administered every day or every other day per institutional practice. An additional 4 cycles of Radium (Ra-223) dichloride at 55 kBq/kg or 0.00149 mCi/kg or 1.49 uCi/kg every 4 weeks will then be administered, resuming 2-3 weeks after completion of the final fraction of SBRT.<br>* Other names: Ra-223;Diagnostic Test: PET Scan<br>* For both arms, the NaF PET will be used to identify discrete osseous lesions which will become index lesions for the study. The simulation scan (either baseline or after 2 cycles of Ra-223) will be used to generate a suitable SBRT radiation plan, per standard practice. If the index lesions are no longer visible after two cycles of Ra-223, we still intend to consolidate the area with radiation. If the lesions are initially radio-occult on the CT and only visible on the NaF PET, we will fuse the pre-treatment NaF PET/CT to the simulation CT after 2 cycles of Ra-223 to delineate the SBRT treatment volumes.<br>* Other names: NaF PET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | The primary outcome is to compare rates of composite PFS between the two treatment arms using bone scan imaging. A patient will be considered to have disease progression if any of the following events occur from the time of protocol randomization to date of last follow-up: a) PSA biochemical progression OR b) Radiographical progression OR c) clinical progression OR d) start of ADT OR e) death from any cause | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, SBRT, Non-castrate Resistant Prostate Cancer, Oligorecurrent Prostate Cancer, SAXON-PC, 21-213, Memorial Sloan Kettering Cancer Center