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

Phase 2
Active, not recruiting
Conditions
Prostate Cancer
Interventions
Drug: Radium dichloride
Diagnostic Test: PET Scan
Registration Number
NCT05133440
Lead Sponsor
Memorial Sloan Kettering Cancer Center
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
12
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Experimental ArmRadium dichlorideParticipants 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. SBRT to the target index lesion(s) should be completed within 30 days after simulation after completion of the 2nd infusion of Radium (Ra-223) dichloride. Specific dose constraints, dosing schedules, and management of SBRT to multiple sites will be at the discretion of the treating Radiation oncologist. The goal is to complete simulation and SBRT within 30 days. Only active or progressive disease is to be treated at the discretion of the treating investigator.
Control Arm:PET ScanParticipants 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. SBRT should begin within 30 days (+/- 7 days) of randomization. Only active or progressive disease is to be treated at the discretion of the treating investigator.
Control Arm:Radium dichlorideParticipants 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. SBRT should begin within 30 days (+/- 7 days) of randomization. Only active or progressive disease is to be treated at the discretion of the treating investigator.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival1 year

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

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (7)

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

🇺🇸

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

🇺🇸

Montvale, New Jersey, United States

University of Colorado (Data Collection Only)

🇺🇸

Aurora, Colorado, United States

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

🇺🇸

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Commack (Limited Protocol Activities)

🇺🇸

Commack, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

🇺🇸

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

🇺🇸

New York, New York, United States

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