Prostatic Neoplasms
Conditions
Brief summary
Eligible subjects must have completed 6 doses of treatment of radium-223 dichloride and experienced no radium-223 dichloride-related SAEs (serious adverse events) or CTCAE (Common Terminology Criteria for Adverse Events) Grade 3 or 4 adverse event during or after the initial course of radium-223 dichloride that led to the discontinuation of treatment. 40 Subjects will be enrolled and will receive up to 6 doses of radium-223 dichloride 50 kBq/kg IV every 4 weeks. The subject will be evaluated for AEs (adverse events) and laboratory tests at each visit every 4 weeks, prior to receiving radium-223 dichloride. After the end of treatment visit the subjects will enter the active follow up period. Related AEs and SAEs and Lab tests will be evaluated at each visit every 4 weeks for the first 12 weeks, then every 12 weeks for up to 2 years after the last dose of radium-223 dichloride. After the 2 years of active follow-up, subjects will enter the long-term follow-up period and will be followed via telephone follow-up at 6-month intervals for late toxicities and survival up to 7 years after the last dose of radium-223 dichloride or until death. Joint safety reviews will regularly take place to oversee safety of the subjects conducted at regular intervals. An interim analysis of the safety data will be conducted during the study.
Interventions
DRUGRadium-223 dichloride (Xofigo, BAY88-8223)
Participants received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate at any given point in time during disease history * CRPC (castration-resistant prostate cancer) with clinical or radiologically confirmed bone progression * Treatment with 6 injections of radium-223 dichloride 50 kBq/kg and no evidence of progression to bone (according to Prostate Cancer Clinical Trials Working Group 2 \[PCWG2\] criteria) during the first course of treatment * Signed written informed consent prior to participating in any study related procedures. Willing and able to comply with the protocol, including follow-up visits and examinations
Exclusion criteria
* History of a radium-223 dichloride-related serious adverse event (SAE) or CTCAE Grade 3 or 4 adverse event (AE) during or after the initial course of radium-223 dichloride treatment that led to the discontinuation of treatment * Less than 30 days from the last dose administered in the initial course of radium-223 dichloride treatment * Visceral metastases 1 cm or greater in largest diameter and / or requiring local or systemic therapeutic intervention, as assessed by abdominal and pelvic magnetic resonance imaging (MRI) / computed tomography (CT) scan and / or chest X-ray within 30 days of the start of treatment * Lymphadenopathy with lymph nodes exceeding 6 cm in short-axis diameter and / or requiring local or systemic therapeutic intervention. Enlarged lymph nodes of any size if the lymphadenopathy is thought to be a contributor to concurrent hydronephrosis. * Current central nervous system (CNS) metastases * Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone) * Treatment with chemotherapy after the initial course of radium-223 dichloride treatment * Prior hemibody external radiotherapy * Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, or rhenium-188 * Any other serious illness or medical conditions * Crohn's disease or ulcerative colitis * History of documented bone marrow dysplasia * Unmanageable fecal incontinence * Imminent or established spinal cord compression based on clinical findings and / or MRI that has not yet been treated * Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AEs) | Up to 2.5 years | 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. |
| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | Up to 2.5 years | 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. |
| Number of Participants With Radium-223 Dichloride-related AEs in the Active Follow-up Period | Up to 2 years after last treatment | 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. |
| Number of Participants With Radium-223 Dichloride-related SAEs in the Active Follow-up Period | Up to 2 years after last treatment | 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. |
| Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Up to 2.5 years | — |
| Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Up to 2.5 years | — |
| Number of Participants Who Discontinued Radium-223 Dichloride Treatment Due to Treatment Emergent AEs or Death | Up to 2.5 years | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 2 years after last treatment | 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. |
| Percentage of Participants With Pain Improvement | Up to 2.5 years | 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. |
| Radiological Progression Free Survival (rPFS) | Up to 2 years after last treatment | 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 First Symptomatic Skeletal Event (SSE) | Up to 2 years after last treatment | 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. |
| SSE-free Survival | Up to 2 years after last treatment | 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. |
| Time to Pain Progression | Up to 2.5 years | 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 Radiological Bone Progression | Up to 2 years after last treatment | 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. |
| Percentage of Participants With Total Alkaline Phosphatase (ALP) Response | Up to 2.5 years | 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. |
| Time to Total ALP Progression | Up to 2 years after last treatment | 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. |
| Percent Change in Total ALP | Baseline and Week 12, Week 24 | — |
| Percentage of Participants With Prostate Specific Antigen (PSA) Response | Up to 2.5 years | 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. |
| Time to PSA Progression | Up to 2 years after last treatment | 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. |
Countries
Finland, Israel, Italy, Norway, Spain, Sweden, United States
Participant flow
Recruitment details
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).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) Participants received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Active Follow up | Death | 20 |
| Active Follow up | Other reason | 1 |
| Active Follow up | Physician Decision | 2 |
| Active Follow up | Progressive disease | 1 |
| Treatment | Adverse Event | 3 |
| Treatment | Clinical progression | 6 |
| Treatment | Radiological progression | 4 |
| Treatment | Study drug never administered | 1 |
| Treatment | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Radium-223 Dichloride (Xofigo, BAY88-8223) |
|---|---|
| Age, Continuous | 71 Years |
| Age, Customized < 65 years | 13 Participants |
| Age, Customized >=65 years | 31 Participants |
| Baseline Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score 0 | 14 Participants |
| Baseline Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score 1 | 27 Participants |
| Baseline Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score 2 | 3 Participants |
| Number of bone lesions 1-5 | 18 Participants |
| Number of bone lesions > 20, not a superscan | 6 Participants |
| Number of bone lesions 6-20 | 15 Participants |
| Number of bone lesions Superscan | 5 Participants |
| Prostate specific antigen (PSA) - mean value | 211.59 microgram per liter STANDARD_DEVIATION 452.84 |
| Prostate specific antigen (PSA) - median value | 67.66 microgram per liter |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 44 Participants |
| Time from initial diagnosis | 80.34 Months |
| Time from initial diagnosis of bone metastasis | 43.12 Months |
| Time since initial treatment with radium-223 dichloride | 6.05 Months |
| Total alkaline phosphatase (ALP) - mean value | 122.60 Unit per liter STANDARD_DEVIATION 118.49 |
| Total alkaline phosphatase (ALP) - median value | 85 Unit per liter |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 44 |
| serious Total, serious adverse events | 13 / 44 |
Outcome results
Primary
Number of Participants Who Discontinued Radium-223 Dichloride Treatment Due to Treatment Emergent AEs or Death
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.
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants Who Discontinued Radium-223 Dichloride Treatment Due to Treatment Emergent AEs or Death | 2 Participants |
Primary
Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Alanine Aminotransferase (U/L) - High | 2 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Alkaline Phosphatase (U/L) - High | 14 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Aspartate Aminotransferase (U/L) - High | 6 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Bilirubin (mg/dL) - High | 1 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Creatinine (mg/dL) - High | 7 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Sodium (mmol/L) - High | 6 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Alanine Aminotransferase (U/L) - Low | 4 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Albumin (g/dL) - Low | 10 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Aspartate Aminotransferase (U/L) - Low | 1 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Bilirubin (mg/dL) - Low | 4 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Creatinine (mg/dL) - Low | 7 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start | Sodium (mmol/L) - Low | 14 Participants |
Primary
Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Eosinophils (GIGA/L) - High | 1 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Ery. Mean Corpuscular HGB Conc. (g/dL) - High | 1 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Ery. Mean Corpuscular Hemoglobin (pg) - High | 16 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Leukocytes (GIGA/L) - High | 5 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Monocytes (GIGA/L) - High | 7 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Neutrophils (GIGA/L) - High | 9 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Platelets (GIGA/L) - High | 1 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Basophils (GIGA/L) - Low | 2 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Eosinophils (GIGA/L) - Low | 7 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Ery. Mean Corpuscular HGB Conc. (g/dL) - Low | 17 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Ery. Mean Corpuscular Hemoglobin (pg) - Low | 4 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Ery. Mean Corpuscular Volume (fL) | 3 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Erythrocytes (T/L) - Low | 43 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Hematocrit (%) - Low | 43 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Hemoglobin (g/dL) - Low | 43 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Leukocytes (GIGA/L) - Low | 21 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Lymphocytes (GIGA/L) - Low | 36 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Monocytes (GIGA/L) - Low | 2 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Neutrophils (GIGA/L) - Low | 10 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Platelets (GIGA/L) - Low | 11 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start | Ery. Mean Corpuscular Volume (fL) - High | 22 Participants |
Primary
Number of Participants With Radium-223 Dichloride-related AEs in the Active Follow-up Period
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.
Time frame: Up to 2 years after last treatment
Population: Active Follow-up Analysis Set: participants who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Radium-223 Dichloride-related AEs in the Active Follow-up Period | 1 Participants |
Primary
Number of Participants With Radium-223 Dichloride-related SAEs in the Active Follow-up Period
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.
Time frame: Up to 2 years after last treatment
Population: Active Follow-up Analysis Set: participants who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Radium-223 Dichloride-related SAEs in the Active Follow-up Period | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (AEs)
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.
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Treatment-emergent Adverse Events (AEs) | 41 Participants |
Primary
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
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.
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 13 Participants |
Post Hoc
Number of Deaths During Study Treatment or Follow-up Period
Time frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Deaths During Study Treatment or Follow-up Period | During Active follow-up Period | 23 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Deaths During Study Treatment or Follow-up Period | During Long-term follow-up Period | 4 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Deaths During Study Treatment or Follow-up Period | During Treatment Period | 1 Participants |
Post Hoc
Number of Participants With Body Weight Changes During the Follow-up Period
Participants were counted once during active follow-up for both increases (using the maximum body weight) and decreases (using the minimum body weight).
Time frame: Up to 2 years after last treatment
Population: Active Follow-up Analysis Set: participants who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Body Weight Changes During the Follow-up Period | Increases < 5% | 23 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Body Weight Changes During the Follow-up Period | Increases 5-10% | 4 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Body Weight Changes During the Follow-up Period | Increases > 10% | 0 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Body Weight Changes During the Follow-up Period | Decreases < 5% | 13 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Body Weight Changes During the Follow-up Period | Decreases 5-10% | 9 Participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Body Weight Changes During the Follow-up Period | Decreases > 10% | 5 Participants |
Post Hoc
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score Worsened to >=3 During the Follow-up Period
Time frame: Up to 2 years after last treatment
Population: Active Follow-up Analysis Set: participants who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score Worsened to >=3 During the Follow-up Period | 4 Participants |
Post Hoc
Number of Participants With New Primary Malignancies During Study Treatment or Follow-up Period
Time frame: Up to 2 years after last treatment
Population: Active Follow-up Analysis Set: participants who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With New Primary Malignancies During Study Treatment or Follow-up Period | 1 Participants |
Post Hoc
Number of Participants With New SSE Related AEs During the Follow-up Period
Time frame: Up to 2 years after last treatment
Population: Active Follow-up Analysis Set: participants who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With New SSE Related AEs During the Follow-up Period | 0 Participants |
Post Hoc
Number of Participants With Significant Meaningful Changes for Clinical Laboratory NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Toxicity Grades During the Follow-up Period
Time frame: Up to 2 years after last treatment
Population: Active Follow-up Analysis Set: participants who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Number of Participants With Significant Meaningful Changes for Clinical Laboratory NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Toxicity Grades During the Follow-up Period | 0 Participants |
Other Pre-specified
Overall Survival
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.
Time frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Overall Survival | 24.4 Months |
Other Pre-specified
Percentage of Participants With Pain Improvement
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.
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Pain Improvement | 12 Week | 0 Percentage of participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Pain Improvement | 24 Week | 0 Percentage of participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Pain Improvement | Anytime | 8.3 Percentage of participants |
Other Pre-specified
Percentage of Participants With Prostate Specific Antigen (PSA) Response
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.
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Prostate Specific Antigen (PSA) Response | 12 Week | 6.3 Percentage of participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Prostate Specific Antigen (PSA) Response | Anytime | 9.1 Percentage of participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Prostate Specific Antigen (PSA) Response | 24 Week | 0 Percentage of participants |
Other Pre-specified
Percentage of Participants With Total Alkaline Phosphatase (ALP) Response
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.
Time frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Total Alkaline Phosphatase (ALP) Response | 24 Week | 30.6 Percentage of participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Total Alkaline Phosphatase (ALP) Response | 12 Week | 39.4 Percentage of participants |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percentage of Participants With Total Alkaline Phosphatase (ALP) Response | Anytime | 43.2 Percentage of participants |
Other Pre-specified
Percent Change in Total ALP
Time frame: Baseline and Week 12, Week 24
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percent Change in Total ALP | Week 12 | -17.1 Percent change | Standard Deviation 32.74 |
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Percent Change in Total ALP | Week 24 | -15.0 Percent change | Standard Deviation 35.1 |
Other Pre-specified
Radiological Progression Free Survival (rPFS)
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 frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Radiological Progression Free Survival (rPFS) | 9.9 Months |
Other Pre-specified
SSE-free Survival
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.
Time frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | SSE-free Survival | 12.8 Months |
Other Pre-specified
Time to First Symptomatic Skeletal Event (SSE)
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.
Time frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Time to First Symptomatic Skeletal Event (SSE) | 16.7 Months |
Other Pre-specified
Time to Pain Progression
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 frame: Up to 2.5 years
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Time to Pain Progression | NA Months |
Other Pre-specified
Time to PSA Progression
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.
Time frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Time to PSA Progression | 2.2 Months |
Other Pre-specified
Time to Radiological Bone Progression
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.
Time frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Time to Radiological Bone Progression | NA Months |
Other Pre-specified
Time to Total ALP Progression
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.
Time frame: Up to 2 years after last treatment
Population: Safety Analysis Set (SAF): all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 Dichloride (Xofigo, BAY88-8223) | Time to Total ALP Progression | NA Months |