Radium-223 Dichloride (BAY88-8223) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients With Bone Metastases

Inclusion Criteria:

- Age ≥ 18 years

- Histologically or cytologically confirmed prostate cancer

- Patients diagnosed with symptomatic progressive bone predominant metastatic
CRPC/HRPC with at least 2 skeletal metastases on imaging with no lung, liver, and/or
brain metastasis (lymph node only metastasis is allowed)

- Symptomatic is defined as either

- Regular (not occasional) use of analgesic medication for cancer related bone
pain (≥ level 1; World Health Organization [WHO] ladder for cancer pain), or

- Treatment with external beam radiation therapy (EBRT) for bone pain (the EBRT
should be within the last 12 weeks before treatment)

- Progressive disease is defined either by:

- The appearance of new bone lesions. If progression is based on new lesion(s) on
imaging only without an increase in prostate specific antigen (PSA), then PSA
values from 3 assessments within the last 6 months must be provided; OR

- In the absence of new bone lesions, 2 subsequent increases in serum PSA over
previous reference value, which should not be more than 6 months before
screening, each measured at least 1 week apart with the last PSA ≥ 5 ng/mL.
(The reference value time point 1, is defined as the last PSA measured before
increases are documented, with subsequent values obtained a minimum of 1 week
apart. If the PSA at time point 3 is greater than the PSA at time point 2, then
eligibility has been met. If the PSA at time point 3 is not greater than the
PSA at time point 2 but, the PSA value at time point 4 and/or time point 5 is
greater than the PSA at time point 2, the patient is eligible assuming that
other criteria are met).

- No intention to use cytotoxic chemotherapy within the next 6 months

- Life expectancy ≥ 6 months

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2

- Adequate hematological, liver, and renal function

- Absolute neutrophil count (ANC) ≥ 1.5 x10^9/L

- Platelet count ≥ 100 x10^9/L

- Hemoglobin ≥ 10.0 g/dL (100 g/L; 6.2 mmol/L)

- 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 > 25 g/L *Any bone imaging techniques as per institutional standard of
care

Exclusion Criteria:

- Treatment with an investigational drug within previous 4 weeks, or planned during
the treatment period or follow-up

- Eligible for first course of docetaxel, i.e., patients who are fit enough, willing,
and who are located where treatment with docetaxel is available

- Treatment with cytotoxic chemotherapy within previous 4 weeks prior to screening, or
failure to recover from adverse events (AEs) due to cytotoxic chemotherapy
administered more than 4 weeks previous prior to screening (however, ongoing
neuropathy is permitted)

- Prior hemibody external radiotherapy is excluded. Patients who received other types
of prior external radiotherapy are allowed provided that the bone marrow function is
assessed and meets the protocol requirements for hemoglobin, absolute neutrophil
count, and platelets

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

- Other malignancy treated within the last 3 years (except non melanoma skin cancer or
low-grade superficial bladder cancer)

- Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) (or
other imaging modality based on institutional standard of care)

- Presence of brain metastases

- Lymphadenopathy exceeding 6 cm in short-axis diameter

- Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent
hydronephrosis.

- Imminent spinal cord compression based on clinical findings and/or magnetic
resonance imaging (MRI). Patients with history of spinal cord compression should
have completely recovered.

- Any other serious illness or medical condition, such as but not limited to:

- Any infection ≥ National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI-CTCAE) version 4.03 Grade 2

- Cardiac Failure New York Heart Association (NYHA) Class III or IV

- Crohn's disease or ulcerative colitis

- Bone marrow dysplasia

- Fecal incontinence