Overview

This trial is active, not recruiting.

Condition prostatic neoplasms
Treatments radium-223 dichloride (xofigo,bay88-8223), abiraterone acetate, prednisone, enzalutamide
Phase phase 2
Target androgen receptor
Sponsor Bayer
Start date December 2013
End date July 2016
Trial size 63 participants
Trial identifier NCT02034552, 16544

Summary

The primary objective in this study is to evaluate bone scan response at Week 24 based on the quantified technetium-99 bone scan lesion area (BSLA). The safety of radium-223 dichloride in combination with abiraterone acetate or enzalutamide will be investigated. The study will evaluate radiological progression free survival, overall survival, and skeletal events. This study will also explore the clinical utility of different imaging modalities (whole body quantified technetium-99 bone scan, DW-MRI and NaF PET-CT scan) and will have a separate central radiological review for applicable secondary and exploratory imaging endpoints. All subjects will be randomized as assigned randomly by the IXRS system in a 1:1:1 ratio into one of the treatment arms: radium-223 dichloride alone, 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks for up to 6 doses; radium-223 dichloride, 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks up to 6 doses together with abiraterone acetate 1,000 mg daily and prednisone 5 mg bid; radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks up to 6 doses together with enzalutamide 160 mg daily.The study will consist of screening, treatment and follow-up periods. Study will continue until disease progression as determined by investigator, or when patient meets criteria for withdrawal from study. Subjects in treatment arms with abiraterone/prednisone or enzalutamide will have the option to continue taking oral study therapy until the end of the study (2 years from the last dose of radium-223 dichloride) if the investigator deems the subject may benefit and there is no clinical or radiological progression. Subjects who discontinue all study treatment prior to 2 years from last radium-223 dichloride treatment will enter active follow-up. During the active follow-up period, the subject will have a safety visit at the clinic every 12 weeks from the EOT for up to 2 years from the last dose of radium-223 dichloride. Beyond 2 years from last radium-223 dichloride treatment,subjects will enter long-term follow-up and will be followed via phone contact at intervals to assess for safety (hematological toxicity and new primary malignancies) and overall survival. A separate long-term safety follow-up study protocol is planned. Once implemented, the study subjects surviving after the end of the active follow-up will be transitioned to this separate long-term safety follow-up protocol.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
radium-223 dichloride (xofigo,bay88-8223)
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses intravenous slow bolus
(Experimental)
radium-223 dichloride (xofigo,bay88-8223)
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses intravenous slow bolus
abiraterone acetate
Abiraterone acetate 1000 mg (4 x 250 mg tablets) taken orally once daily for up to two years following last dose of radium-223 dichloride
prednisone
Prednisone 5 mg capsule taken orally twice daily for up to two years following last dose of radium-223 dichloride
(Experimental)
radium-223 dichloride (xofigo,bay88-8223)
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses intravenous slow bolus
enzalutamide
Enzalutamide 160 mg (four 40 mg capsules) taken orally once daily for up to two years following last dose of radium-223 dichloride

Primary Outcomes

Measure
Patient Bone Scan Response
time frame: At 24 weeks

Secondary Outcomes

Measure
radiological progression-free survival (rPFS)
time frame: from randomization to radiological disease progression or death from any cause, up to 30 months
symptomatic skeletal event-free survival (SSE-FS)
time frame: From randomization to the earlier SSE or death, up to 30 months
Time to first symptomatic skeletal event(SSE)
time frame: From randomization to first SSE or death, up to 30 months
Overall Survival (OS)
time frame: From randomization to the date of radiological disease progression, up to 7.5 years
time to radiological bone progression by treatment group
time frame: time to radiological bone progression up to 30 months
Number of participants with treatment-emergent adverse events as a measure of safety and tolerability
time frame: Up to 30 months
Number of participants with serious adverse events as a measure of safety and tolerability
time frame: Up to 7.5 years

Eligibility Criteria

Male participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically confirmed adenocarcinoma of the prostate - Known castration-resistant disease - Serum PSA ≥2 ng/mL (μg/L) - Multiple skeletal metastases (≥2 hot spots) on bone scan - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2. - Life expectancy ≥6 months - Adequate hematologic, hepatic, and renal function Exclusion Criteria: - History of visceral metastasis, or visceral metastases - Malignant lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter - Medical condition that would make prednisone (corticosteroid) use contraindicated - Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone bid - Treatment with more than one chemotherapy agent for prostate cancer - Prior systemic radiotherapy and hemibody external radiotherapy - History of pituitary or adrenal dysfunction - Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone) - Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy - History of seizures (taking/not taking anticonvulsants), arteriovenous malformation in the brain, head trauma with loss of consciousness - Central nervous system (CNS) metastases

Additional Information

Official title A Randomized Open-label Phase IIa Study Evaluating Quantified Bone Scan Response Following Treatment With Radium-223 Dichloride Alone or in Combination With Abiraterone Acetate or Enzalutamide in Subjects With Castration-resistant Prostate Cancer Who Have Bone Metastases
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Bayer.