We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01934790
Recruitment Status : Completed
First Posted : September 4, 2013
Results First Posted : September 29, 2016
Last Update Posted : March 26, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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.


Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 22, 2013
Actual Primary Completion Date : June 4, 2015
Actual Study Completion Date : April 12, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: 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.
Drug: 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.




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (AEs) [ Time Frame: 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.

  2. Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: 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.

  3. Number of Participants With Radium-223 Dichloride-related AEs in the Active Follow-up Period [ Time Frame: 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.

  4. Number of Participants With Radium-223 Dichloride-related SAEs in the Active Follow-up Period [ Time Frame: 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.

  5. Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start [ Time Frame: Up to 2.5 years ]
  6. Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start [ Time Frame: Up to 2.5 years ]
  7. Number of Participants Who Discontinued Radium-223 Dichloride Treatment Due to Treatment Emergent AEs or Death [ Time Frame: 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 Outcome Measures:
  1. Radiological Progression Free Survival (rPFS) [ Time Frame: 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.

  2. Time to Radiological Bone Progression [ Time Frame: 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.

  3. Percentage of Participants With Total Alkaline Phosphatase (ALP) Response [ Time Frame: 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.

  4. Time to Total ALP Progression [ Time Frame: 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.

  5. Percent Change in Total ALP [ Time Frame: Baseline and Week 12, Week 24 ]
  6. Percentage of Participants With Prostate Specific Antigen (PSA) Response [ Time Frame: 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.

  7. Time to PSA Progression [ Time Frame: 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.

  8. Overall Survival [ Time Frame: 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.

  9. Percentage of Participants With Pain Improvement [ Time Frame: 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.

  10. Time to Pain Progression [ Time Frame: 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.

  11. Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: 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.

  12. SSE-free Survival [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01934790


Locations
Layout table for location information
United States, Louisiana
New Orleans, Louisiana, United States, 70112
United States, Nebraska
Omaha, Nebraska, United States, 68130
United States, New York
Syracuse, New York, United States, 13210
Finland
Kuopio, Finland, 70210
Israel
Haifa, Israel, 3109601
Jerusalem, Israel, 9112001
Kfar Saba, Israel, 4428164
Petah Tikva, Israel, 4941492
Italy
Forlì-Cesena, Emilia-Romagna, Italy, 47014
Milano, Lombardia, Italy, 20133
Norway
Bergen, Norway, 5021
Lørenskog, Norway, 1478
Spain
Córdoba, Andalucía, Spain, 14004
Barcelona, Spain, 08025
Málaga, Spain, 29010
Sweden
Umeå, Sweden, 901 85
Sponsors and Collaborators
Bayer
Investigators
Layout table for investigator information
Study Director: Bayer Study Director Bayer
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01934790    
Other Study ID Numbers: 16506
2013-003046-17 ( EudraCT Number )
First Posted: September 4, 2013    Key Record Dates
Results First Posted: September 29, 2016
Last Update Posted: March 26, 2018
Last Verified: March 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Radium Ra 223 dichloride
Antineoplastic Agents