Trial Outcomes & Findings for Re-treatment Safety of Radium-223 Dichloride in Castration-resistant Prostate Cancer With Bone Metastases (NCT NCT01934790)

Overall, 59 participants were screened in 7 countries worldwide, from 22-Dec-2013 (first patient first visit) to 12-Apr-2017 (last patient last visit).

The study was conducted at 16 study centers that screened 59 participants. Of them, 14 were screening failures and the remaining 45 participants were assigned to treatment.

Re-treatment Safety of Radium-223 Dichloride in Castration-resistant Prostate Cancer With Bone Metastases

An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom, or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. A treatment-emergent adverse events (TEAE) is defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of radium-223 dichloride.

TESAE occurred after the start of radium-223 dichloride treatment until 30 days after the last dose and results in death; is life-threatening; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly / birth defect; is another medically important serious event as judged by the investigator; or is an occurrence of leukemia, myelodysplastic syndrome, aplastic anemia, myelofibrosis, and primary bone cancer or any other new primary malignancy, such as acute myeloid leukemia.

An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom, or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study.

Treatment-related SAE is any SAE that, according to the investigator's causality assessment, is possibly or probably related to treatment with radium-223 dichloride.

An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom, or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. A treatment-emergent adverse events (TEAE) is defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of radium-223 dichloride.

Radiological progression-free survival (rPFS) was defined as the time from the treatment start date to the date of radiological disease progression or death from any cause (if death occurred before such progression), as documented by the investigator. Participants not experiencing death or radiological disease progression at the database cutoff for primary completion were censored at the last radiological disease progression assessment.

Time to radiological bone progression was defined as the time (days) from the treatment start date to the date of radiological bone progression (according to the adapted PCWG2 \[Prostate Cancer Clinical Trials Working Group 2\] criteria), as documented by the investigator. Participants not experiencing radiological bone progression at the database cutoff for primary completion were censored at the last radiological bone progression assessment.

Total alkaline phosphatase (ALP) response was defined as ≥ 30% reduction of the blood total ALP level compared with the baseline values. Total ALP response rate was defined as the number of participants with total ALP response divided by the total number of participants evaluable for total ALP response.

Total ALP progression was defined as a ≥ 25% increase above the nadir (lowest baseline or post-baseline) value to at least 1.5 x ULN (upper limit of normal). The time to total ALP progression was defined as the time (days) from the treatment start date to the date of first total ALP progression. Participants not experiencing ALP progression at the database cutoff date, whether or not surviving, were censored at the last ALP laboratory assessment.

Prostate specific antigen (PSA) response was defined as a ≥ 30% reduction of blood PSA level compared with the baseline value, confirmed by a second subsequent PSA value with a ≥ 30% reduction from baseline approximately 4 or more weeks later. Prostate specific antigen response rate was defined as the number of participants with PSA response divided by the total number of participants evaluable for PSA response.

Prostate specific antigen progression was defined as a ≥ 25% increase above the nadir (lowest baseline or post-baseline) value, and an increase in absolute value of ≥ 2 ng/mL above nadir. The time to PSA progression was defined as the time (days) from the treatment start date to the date of first PSA progression. Participants without PSA progression as of the database cutoff for primary completion, whether or not surviving, were censored at the last PSA laboratory assessment.

Overall survival (OS) was defined as the time (days) from the treatment start date to the date of death due to any cause. For participants who were still alive or who were lost to follow-up as of the database cutoff date for the primary completion, OS was censored at the last known alive date on or prior to the database cutoff date.

Pain improvement was defined in evaluable participants (participants with worst pain score \[WPS\] of 4 at baseline) as a 30% and 2-point decrease in WPS over 2 consecutive measurements conducted at least 4 weeks apart, without an increase in pain management. Pain improvement rate was the number of participants with pain improvement, divided by the total number of evaluable participants WPS was the mean of the WPS in the last 24 hours from the preceding 7 days.

Pain progression was defined in participants evaluable for pain progression at baseline, i.e., participants with a WPS of ≤ 7 at the baseline assessment. Pain assessment occurred daily for 1 week, beginning 1 week prior to each visit and including the day of the visit. An evaluable pain assessment interval required completion of a minimum of 4 out of 7 daily questions. Pain progression was defined as the occurrence of either a pain increase or an increase in pain management with respect to baseline, whichever occurred first.

Time to first symptomatic skeletal event (SSE) is the time (days) from the treatment start date to the first SSE on or following the start date. Participants not experiencing an SSE at the database cutoff date for primary completion, whether or not surviving, were censored at the last assessment for SSEs.

The SSE-FS is the time (days) from the treatment start date to the first SSE on or following the start date or death, whichever occurred first. Participants not experiencing death or an SSE at the database cutoff date for primary completion were censored at the last assessment for SSEs.

Participants were counted once during active follow-up for both increases (using the maximum body weight) and decreases (using the minimum body weight).