Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone

Inclusion Criteria:

- Asymptomatic or symptomatic hormone naïve men with testosterone levels ≥100 ng/dL with
previously treated localized prostate cancer who now have rising PSA's and five or
fewer bone metastases.

- Subjects who have been previously treated with definitive and/or adjuvant/salvage
radiotherapy to the primary site and/or regional lymph nodes with concurrent ADT are
allowed if the last hormone therapy delivered > 6 months prior. Subjects who have had
fewer than 6 weeks of bicalutamide monotherapy for any reason within the 6 months
prior to enrollment are eligible for the study, providing they have been off of the
drug for at least 30 days prior to enrollment.

- Histologic confirmation of Prostate Adenocarcinoma diagnosis.

- Age ≥ 18 years.

- Life expectancy of at least 2 years.

- Acceptable hematology and serum biochemistry screening values:

- White Blood Cell Count (WBC) ≥ 3,000/mm3

- Absolute Neutrophil Count (ANC) ≥ 1,500/mm3

- Platelet (PLT) count ≥ 100,000/mm3

- Hemoglobin (HGB) ≥ 10 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

- Albumin > 2.5 mg/dL

- Willing and able to comply with the protocol, including follow-up visits and
examinations.

- Karnofsky Performance Score >60 or ECOG equivalent.

- Radiographic confirmation of oligometastatic diagnosis via Bone Scan validated by
either CT scan or MRI or PET/CT with Fluciclovine within the past 90 days.

- 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 ICF
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

- Able to provide informed consent and willing to sign an approved consent form that
conforms to federal and institutional guidelines.

Exclusion Criteria:

- Men with known brain or visceral metastases (except regional lymph nodes as defined by
section 5.2.5) defined by CT or MRI Imaging of the abdomen or pelvis.

- Men who have had LHRH agonist or antagonist hormone therapy in the prior six months.

- Men with >5 bony metastases.

- Men with baseline serum Testosterone <100 ng/dL.

- Men with new or progressing lymphadenopathy clearly consistent with prostate
metastasis on imaging or proven by pathologic biopsy at any time three months or later
following their initial definitive therapy.

- Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or
lymphomatous/hematogenous malignancy unless continually disease free for a minimum of
3 years. All patients with in situ carcinoma are eligible for this study (for example,
carcinoma in situ of the oral cavity is eligible) except patients with carcinoma of
the bladder (including in situ bladder cancer or superficial bladder cancer).

- Use of finasteride within 30 days prior to therapy PSA should not be obtained prior to
30 days after stopping finasteride.

- Use of dutasteride within 90 days prior to therapy. PSA should not be obtained prior
to 90 days after stopping dutasteride.

- Previous or concurrent cytotoxic chemotherapy for prostate cancer.

- Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153,
rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony
metastases.

- Men who will receive radical prostatectomy to the primary site.

- Imminent spinal cord compression based on clinical findings and/or magnetic resonance
imaging (MRI). Spinal Cord compression will be defined as 360 degree circumferential
obliteration of T2 cerebrospinal fluid signal around the spinal cord. Treatment should
be completed for spinal cord compression.

- Severe, active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for liver function and coagulation
parameters are not required for entry into this protocol. (Patients on Coumadin
or other blood thinning agents are eligible for this study.)

- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;
note, however, that HIV testing is not required for entry into this protocol. The
need to exclude patients with AIDS from this protocol is necessary because the
treatments involved in this protocol may be significantly immunosuppressive.

- Cardiac failure New York Heart Association (NYHA) III or IV Crohn's disease or
ulcerative colitis.

- Bone marrow dysplasia.

- Fecal incontinence.

- Any condition which, in the investigator's opinion, makes the subject unsuitable for
trial participation.