- ICH GCP
- US Clinical Trials Registry
- 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)
July 4, 2019 updated by: Bayer
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
68
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Arizona
-
Scottsdale, Arizona, United States, 85251
-
Tucson, Arizona, United States, 85704
-
-
California
-
Los Angeles, California, United States, 90033
-
-
Connecticut
-
New Haven, Connecticut, United States, 06520
-
-
Delaware
-
Newark, Delaware, United States, 19713
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20007
-
-
Florida
-
Plantation, Florida, United States, 33324
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
-
-
Louisiana
-
New Orleans, Louisiana, United States, 70112
-
Shreveport, Louisiana, United States, 71103
-
-
Maryland
-
Rockville, Maryland, United States, 20850
-
-
Michigan
-
Detroit, Michigan, United States, 48201
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
-
-
Nebraska
-
Omaha, Nebraska, United States, 68130
-
-
New York
-
Bronx, New York, United States, 10467-2490
-
Syracuse, New York, United States, 13210
-
-
Oregon
-
Springfield, Oregon, United States, 97477
-
-
Texas
-
Houston, Texas, United States, 77027
-
-
Washington
-
Seattle, Washington, United States, 98109
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Radium-223 dichloride (Xofigo, BAY88-8223)
|
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus
|
Experimental: Radium-223 with abiraterone&prednisone
|
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus
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 5 mg capsule taken orally twice daily for up to two years following last dose of radium-223 dichloride
|
Experimental: Radium-223 with enzalutamide
|
Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus
Enzalutamide 160 mg (four 40 mg capsules) taken orally once daily for up to two years following last dose of radium-223 dichloride
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient Bone Scan Response Rate
Time Frame: At 24 weeks
|
Radiological bone scan response based on change from baseline of digitized technetium-99 bone scans using computer-aided detection software.
Responder (R): 30% or greater resolution of the BSLA compared to baseline.
Stable Disease (SD): Not meeting the criteria for R, PD, or UE.
Progressive Disease (PD): Two or more new areas of radiotracer uptake attributable to metastatic disease in regions of bone that had not previously shown radiotracer uptake or greater than 30% increase from baseline in BSLA attributable to metastatic disease.
Unable to Evaluate (UE): Assigned if bone scan results cannot be interpreted due to inconsistent image acquisition parameters compared to the reference scan, incomplete imaging, or other similar technical deficiencies.
|
At 24 weeks
|
Bone Scan Lesion Area
Time Frame: At 24 weeks
|
Bone scan lesion area was defined as the sum of the pixel areas (cm2) of the set of the whole body technetium-99 bone scan imaging pixels identified as bone lesion.
|
At 24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Radiological Progression Free Survival
Time Frame: From randomization to radiological disease progression or death from any cause (about 30.82 months )
|
From randomization to radiological disease progression or death from any cause (about 30.82 months )
|
Time to Radiological Progression
Time Frame: From the randomization date to the date of radiological disease progression (about 30.82months)
|
From the randomization date to the date of radiological disease progression (about 30.82months)
|
Time to Radiological Bone Progression
Time Frame: From the randomization date to the date of radiological bone progression (about 30.82 months)
|
From the randomization date to the date of radiological bone progression (about 30.82 months)
|
Time to First Symptomatic Skeletal Event
Time Frame: From the randomization date to the first SSE on or following the randomization date (about 30.82 months)
|
From the randomization date to the first SSE on or following the randomization date (about 30.82 months)
|
Symptomatic Skeletal Event-free Survival
Time Frame: From the randomization date to the first SSE on or following the randomization date or death, whichever occurred first (about 32.39 months)
|
From the randomization date to the first SSE on or following the randomization date or death, whichever occurred first (about 32.39 months)
|
Overall Survival
Time Frame: From the randomization date to the date of death due to any cause (about 42.94 months)
|
From the randomization date to the date of death due to any cause (about 42.94 months)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 7, 2014
Primary Completion (Actual)
July 15, 2016
Study Completion (Actual)
June 26, 2018
Study Registration Dates
First Submitted
December 16, 2013
First Submitted That Met QC Criteria
January 10, 2014
First Posted (Estimate)
January 13, 2014
Study Record Updates
Last Update Posted (Actual)
July 23, 2019
Last Update Submitted That Met QC Criteria
July 4, 2019
Last Verified
July 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Steroid Synthesis Inhibitors
- Prednisone
- Abiraterone Acetate
- Radium Ra 223 dichloride
Other Study ID Numbers
- 16544
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostatic Neoplasms
-
Technische Universität DresdenRecruitingOligometastatic Disease | Prostatic Cancer, Castration-ResistantGermany
-
Australian and New Zealand Urogenital and Prostate...Peter MacCallum Cancer Centre, AustraliaRecruitingCastration Resistant Prostatic CancerAustralia
-
British Columbia Cancer AgencySanofi; Ozmosis Research Inc.UnknownMetastatic Castration-Resistant Prostatic CancerCanada, Australia
-
Janssen Research & Development, LLCCompletedCastration-Resistant Prostatic NeoplasmsCanada, Belgium, United States, Spain, Netherlands, Italy, Russian Federation
-
Universität des SaarlandesRecruitingProstate Cancer Metastatic | Advanced Prostate Carcinoma | Castration Resistant Prostatic CancerGermany
-
Yinghao SunNot yet recruitingCastration-Resistant Prostatic Cancer
-
Institut Claudius RegaudWithdrawnProstatic Cancer, Castration-ResistantFrance
-
University Hospital, GrenobleTerminatedCastration-resistant Prostate CancerFrance
-
Michael Graham PhD, MDUniversity of Iowa; Holden Comprehensive Cancer CenterActive, not recruitingProstate Cancer | Prostatic Neoplasms, Castration-Resistant | Prostatic Neoplasm | Prostatic Cancer Recurrent | Prostatic Cancer MetastaticUnited States
-
Rio de Janeiro State UniversityCompletedProstatic Cancer | Prostatic NeoplasmBrazil
Clinical Trials on Radium-223 dichloride (Xofigo, BAY88-8223)
-
BayerActive, not recruitingMetastatic Castration-resistant Prostate CancerUnited States, Austria, Czechia, Israel, Italy, Germany, United Kingdom, France, Mexico, Belgium, Canada, Colombia, Greece, Luxembourg, Netherlands, Spain, Denmark, Sweden, Argentina, Portugal
-
BayerCompletedProstate CancerUnited States
-
BayerCompletedMetastatic Castration Resistant Prostate Cancer (mCRPC)United States
-
BayerCompletedProstatic NeoplasmsChina, Singapore, Taiwan, Korea, Republic of
-
BayerCompletedBone Metastatic Castration-resistant Prostate CancerGermany, Netherlands, Denmark
-
BayerCompletedProstatic Neoplasms, Castration-ResistantUnited States