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

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

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

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