Back to resultsRe-treatment Safety of Radium-223 Dichloride in Castration-resistant Prostate Cancer With Bone Metastases
Primary Purpose
Prostatic Neoplasms
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Radium-223 dichloride (Xofigo, BAY88-8223)
Sponsored by
About this trial
This is an interventional treatment trial for Prostatic Neoplasms
Eligibility Criteria
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)
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Radium-223 dichloride (Xofigo, BAY88-8223)
Arm Description
Participants received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start
Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01934790
Brief Title
Re-treatment Safety of Radium-223 Dichloride in Castration-resistant Prostate Cancer With Bone Metastases
Official Title
A Re-treatment Safety Study of Radium-223 Dichloride in Subjects With Castration-resistant Prostate Cancer With Bone Metastases Who Received an Initial Course of Six Doses of Radium-223 Dichloride 50 kBq/kg Every Four Weeks
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
December 22, 2013 (Actual)
Primary Completion Date
June 4, 2015 (Actual)
Study Completion Date
April 12, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Radium-223 dichloride (Xofigo, BAY88-8223)
Arm Type
Experimental
Arm Description
Participants received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.
Intervention Type
Drug
Intervention Name(s)
Radium-223 dichloride (Xofigo, BAY88-8223)
Intervention Description
Participants received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (AEs)
Description
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
Title
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Description
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
Title
Number of Participants With Radium-223 Dichloride-related AEs in the Active Follow-up Period
Description
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
Title
Number of Participants With Radium-223 Dichloride-related SAEs in the Active Follow-up Period
Description
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
Title
Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start
Time Frame
Up to 2.5 years
Title
Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start
Time Frame
Up to 2.5 years
Title
Number of Participants Who Discontinued Radium-223 Dichloride Treatment Due to Treatment Emergent AEs or Death
Description
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
Other Pre-specified Outcome Measures:
Title
Radiological Progression Free Survival (rPFS)
Description
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
Title
Time to Radiological Bone Progression
Description
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
Title
Percentage of Participants With Total Alkaline Phosphatase (ALP) Response
Description
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
Title
Time to Total ALP Progression
Description
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
Title
Percent Change in Total ALP
Time Frame
Baseline and Week 12, Week 24
Title
Percentage of Participants With Prostate Specific Antigen (PSA) Response
Description
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
Title
Time to PSA Progression
Description
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
Title
Overall Survival
Description
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
Title
Percentage of Participants With Pain Improvement
Description
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
Title
Time to Pain Progression
Description
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
Title
Time to First Symptomatic Skeletal Event (SSE)
Description
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
Title
SSE-free Survival
Description
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
City
Kuopio
ZIP/Postal Code
70210
Country
Finland
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
City
Kfar Saba
ZIP/Postal Code
4428164
Country
Israel
City
Petah Tikva
ZIP/Postal Code
4941492
Country
Israel
City
Forlì-Cesena
State/Province
Emilia-Romagna
ZIP/Postal Code
47014
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Bergen
ZIP/Postal Code
5021
Country
Norway
City
Lørenskog
ZIP/Postal Code
1478
Country
Norway
City
Córdoba
State/Province
Andalucía
ZIP/Postal Code
14004
Country
Spain
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
City
Málaga
ZIP/Postal Code
29010
Country
Spain
City
Umeå
ZIP/Postal Code
901 85
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
31442327
Citation
Sartor O, Heinrich D, Mariados N, Mendez Vidal MJ, Keizman D, Thellenberg Karlsson C, Peer A, Procopio G, Frank SJ, Pulkkanen K, Rosenbaum E, Severi S, Trigo J, Trandafir L, Wagner V, Li R, Nordquist LT. Re-treatment with radium-223: 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases. Prostate. 2019 Oct;79(14):1683-1691. doi: 10.1002/pros.23893. Epub 2019 Aug 23.
Results Reference
derived
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe.
Learn more about this trial
Re-treatment Safety of Radium-223 Dichloride in Castration-resistant Prostate Cancer With Bone Metastases
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