Radium Ra 223 Dichloride, Hormone Therapy and Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Prostate Cancer

PRIMARY OBJECTIVES:

I. To assess the time to treatment failure (TTF) in patients who initiated the protocol
regimen of androgen deprivation therapy (ADT) with stereotactic body radiation therapy (SBRT)
and radium Ra 223 dichloride and received at least one dose with radium Ra 223 dichloride.

SECONDARY OBJECTIVES:

I. To assess the safety of adding radium Ra 223 dichloride to SBRT and ADT in patients with
oligometastatic castration sensitive prostate cancer.

II. To assess the prostate-specific antigen (PSA) and overall response rate (ORR) after 6
cycles of radium Ra 223 dichloride (cycle 8 day 1).

III. To assess the progression-free survival (PFS) in patients with oligometastatic
castration sensitive prostate cancer who initiated the protocol regimen of ADT with SBRT and
radium Ra 223 dichloride and received at least one dose of radium Ra 223 dichloride.

IV. To assess time to bone specific PFS in patients with oligometastatic castration sensitive
prostate cancer who initiated the protocol regimen of ADT with SBRT and radium Ra 223
dichloride and received at least one dose of radium Ra 223 dichloride.

V. To assess overall survival, complete response rate, duration of response, and duration of
overall complete response and duration of stable disease in patients with oligometastatic
castration sensitive prostate cancer who initiated the protocol regimen of ADT with SBRT and
radium Ra 223 dichloride.

VI. To assess long-term toxicities during 5-year follow-up in patients with oligometastatic
castration sensitive prostate cancer who initiated the protocol regimen of ADT with SBRT and
radium Ra 223 dichloride and received at least one dose of radium Ra 223 dichloride.

TERTIARY OBJECTIVES:

I. To perform exploratory analysis of primary or metastatic tumor mutation patterns in this
study population at baseline.

II. To identify immune system factors in the blood that change during the course of
ADT-radiotherapy for metastatic prostate cancer.

III. To describe the rate of normalization of the total alkaline phosphatase level (defined
as a return to a value within the normal range) at the end of protocol therapy in patients
oligometastatic castration sensitive prostate cancer with total alkaline phosphatase values
above the upper limit of the normal range at baseline.

OUTLINE:

Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate
or goserelin acetate, or degarelix for up to 32 weeks. Patients also undergo 3-5 fractions of
SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223
dichloride intravenously (IV) over 1 minute on day 1 of courses 2-7. Treatment repeats every
28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

Inclusion Criteria:

- Documented informed consent of participant and/or legally authorized representative

- Agreement to provide archival primary or metastatic tumor tissue if available

- Eastern Cooperative Oncology Group (ECOG) =< 2

- Life expectancy > 12 months

- Histologic diagnosis of prostate adenocarcinoma

* Pure small cell carcinoma will be excluded; however, component of neuroendocrine
/small cell differentiation will be allowed provided that adenocarcinoma constitutes
majority of the tissue specimen

- Stage M1

* Metastatic disease can be documented by bone scan or computed tomography (CT) scan
or magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT or the
combination of these tests

- Up to 4 metastatic lesions:

- Must have at least 1 bone lesion AND each non-visceral lesion should be less than
5 cm

- Visceral lesions will be limited to one lung lesion (< 2 cm) or one lymph node;
no liver lesions allowed; lymph nodes allowed provided they are not in a field of
prior radiation, and if amenable to SBRT (to be reviewed by principal
investigator [PI])

- Two lesions can be in close proximity (i.e. within 5 cm of each other) if they meet
radiation SBRT normal tissue toxicity requirements

- If have untreated primary prostate cancer: must undergo debulking prostatectomy

- If had prior definitive radiation therapy to the prostate: no evidence of locally
persistent or recurrent prostate cancer on digital rectal exam (DRE) and imaging
studies (CT or MRI); retreatment to local residual-recurrent disease will result in
potential eligibility to be reviewed by PI on a case-by-case basis

- Does not have castration resistant disease

* Castration resistance defined as progression of disease despite serum testosterone
level of < 50 ng/dL

- PSA >= 0.2 prior to start of androgen deprivation treatment

- Initiated 28 (+ 7) days of androgen deprivation therapy (ADT) prior to day 1 of
protocol therapy

* Only luteinizing hormone-releasing hormone (LHRH) agonist/antagonist treatment is
considered ADT, bicalutamide or other antiandrogens used alone do not count

- May have received prior hormonal therapy in the context of definitive treatment of a
primary tumor

* Patients may have had one prior systemic non-chemotherapeutic treatment (i.e.
immunotherapy, receptor tyrosine kinase inhibitor, antiangiogenic agent,
differentiating agent) for recurrent or metastatic disease

- Must have refused standard of care chemotherapy for metastatic disease

- Recovered from all acute side-effects (except alopecia) related to previous systemic
therapy

- Absolute neutrophil count (ANC) >= 1,500/mm^3 (to be performed within 14 days prior to
day 1 of protocol therapy)

* NOTE: growth factor support is not permitted to normalize baseline ANC parameters,
however subsequent growth factor administration is permitted as standard supportive
care

- Platelets >= 100,000/mm^3 (to be performed within 14 days prior to day 1 of protocol
therapy)

* NOTE: transfusion of blood products are not allowed to normalize baseline blood
parameters, however subsequent transfusions are allowed per standard supportive care
guidelines

- Hemoglobin (HgB) >= 9.0 g/dL (to be performed within 14 days prior to day 1 of
protocol therapy)

* NOTE: transfusion of blood products are not allowed to normalize baseline blood
parameters, however subsequent transfusions are allowed per standard supportive care
guidelines

- Total serum bilirubin =< 2 x upper limit of normal (ULN) (to be performed within 14
days prior to day 1 of protocol therapy)

- Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 14 days prior to
day 1 of protocol therapy)

- Alanine aminotransferase (ALT) =< 2.5 x ULN (to be performed within 14 days prior to
day 1 of protocol therapy)

- Creatinine =< 2.5 mg/dL (to be performed within 14 days prior to day 1 of protocol
therapy)

Exclusion Criteria:

- Prior radium Ra 223 dichloride

- Prior or concomitant chemotherapy for metastatic or recurrent disease with the
following exceptions:

- Prior chemotherapy for local primary disease is permitted

- Bisphosphonates or receptor activator of nuclear factor kappa-Β (RANK) ligand
inhibitors are allowed at doses and schedule consistent with the treatment or
prevention of osteoporosis

- Prior radiation treatment for metastatic disease

- Concomitant radiation treatment to primary prostate site

- Orchiectomy

- Unstable medical comorbidities (i.e. uncontrolled cardiac comorbidities)

- Metastases that in the judgment of investigator-radiologist are not amenable to SBRT

- History of brain metastases or who currently have treated or untreated brain
metastases

- Uncontrolled human immunodeficiency virus (HIV) infection

- Any other condition that would, in the investigator's judgement, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures

- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)