A Study of Alpharadin With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC)

DLT was defined as - Absolute neutrophil count grade greater than or equal to (>=) 4 (Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0: less than [<] 0.5 × 109 per Liter) lasting longer than 7 days without fever despite granulocyte colony-stimulating factor (G-CSF) support). Platelet count Grade >= 4 (CTCAE, v4.0: < 25× 109/L) lasting longer than 7 days. Diarrhea Grade >= 3 (CTAE, v4.0: increase of >= 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care in activities of daily living) in spite of optimal use of antidiarrheal medication. Vomiting or constipation Grade >= 4 (CTCAE, v4.0: life-threatening consequences; urgent intervention indicated). Febrile neutropenia Grade >= 3 (CTCAE, v4.0).

Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in patient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Any physical examination finding that was classified by the investigator as a clinically significant change (compared with previous examination) was considered an AE, documented on the eCRF, and followed until the outcome was known. The below physical examination findings were recorded and reported. GDASC = General disorders and administration site conditions MND = Metabolism and nutrition disorders SSTD= Skin and subcutaneous tissue disorders MCTD = Musculoskeletal and connective tissue disorders IPPC = Injury, poisoning and procedural complications RTMD = Respiratory, thoracic and mediastinal disorders NBMU = Neoplasms benign, malignant and unspecified (include cysts and polyps) In the below table.

Long-term radiation toxicity included incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukemia, myelodysplastic syndrome, and aplastic anemia).

Weighted mean area under the curve for the below bone turnover biomarkers were evaluated, ICTP = pyridinoline cross-linked carboxyterminal telopeptide P1NP = N-terminal peptide of procollagen type 1 uCTX-1 = urine C-telopeptide 1

Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least 1 week apart.

CTCs were measured to follow the evolution of the level of CTCs after treatment.

Time to first radiologic or clinical progression is determined by one of the following:

• For soft tissue lesions, the determination is based on Response Evaluation Criteria in Solid Tumors 1.1.
• For bone disease, the determination is based on Prostate Cancer Working Cohort 2 (PCWG2) definitions, which require the appearance of at least 2 new lesions with a confirmatory bone scan at least 6 or more weeks later. For clinical progression, the investigators followed the recommendations of the PCWG25 and used their clinical judgment to determine clinical progression.

PFS defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (radiological or clinical, whichever was earlier) or death (if death occurred before progression was documented). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.

The overall survival (OS) time in days was calculated as number of days since the day of first dose of study medication until the date of death.

The subject completed the full BPI (short form) paper questionnaire, and clinical staff completed the analgesic log. The test consists of 10 questions addressing severity, location, chronicity, and amount of relief. In question 3, subjects with pain are asked to evaluate the severity of pain at worst in the past 24 hours in a 0 to 10 scale, with 0 indicating no pain, and 10 indicating the worst pain.