Clinical trial NCT02034552: A Randomized Phase IIa Efficacy and Safety Study of Radium-223 Dichloride With Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (CRPC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostatic Neoplasms
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-01-13
Enrollment: 68
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 \[diffusion-weighted magnetic resonance imaging\] and NaF \[sodium fluoride\] PET-CT \[positron emission tomography-computed tomography\] 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 (interactive voice / web response system) 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 \[National Institute of Standards and Technology\] 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 (twice daily); 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 (end of treatment) 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.


Eligibility criteria: 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

Primary outcomes:
measure: Patient Bone Scan Response Rate
timeFrame: At 24 weeks
measure: Bone Scan Lesion Area
timeFrame: At 24 weeks
Secondary outcomes:
measure: Radiological Progression Free Survival
timeFrame: From randomization to radiological disease progression or death from any cause (about 30.82 months )
measure: Time to Radiological Progression
timeFrame: From the randomization date to the date of radiological disease progression (about 30.82months)
measure: Time to Radiological Bone Progression
timeFrame: From the randomization date to the date of radiological bone progression (about 30.82 months)
measure: Time to First Symptomatic Skeletal Event
timeFrame: From the randomization date to the first SSE on or following the randomization date (about 30.82 months)
measure: Symptomatic Skeletal Event-free Survival
timeFrame: From the randomization date to the first SSE on or following the randomization date or death, whichever occurred first (about 32.39 months)
measure: Overall Survival
timeFrame: From the randomization date to the date of death due to any cause (about 42.94 months)
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Newark
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Plantation
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Rockville
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Bronx
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Springfield
country: United States
state: Oregon
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Petrylak DP, Vaishampayan UN, Patel KR, Higano CS, Albany C, Dawson NA, Mehlhaff BA, Quinn DI, Nordquist LT, Wagner VJ, Siegel J, Trandafir L, Sartor O. A randomized phase IIa study of quantified bone scan response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride alone or in combination with abiraterone acetate/prednisone or enzalutamide. ESMO Open. 2021 Apr;6(2):100082. doi: 10.1016/j.esmoop.2021.100082. Epub 2021 Mar 19.