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A Randomized Phase IIa Efficacy and Safety Study of Radium-223 Dichloride With Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (CRPC)

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ClinicalTrials.gov Identifier: NCT02034552
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : July 2, 2017
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 30, 2013
Actual Primary Completion Date : July 15, 2016
Actual Study Completion Date : June 26, 2018


Arm Intervention/treatment
Experimental: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: 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 Drug: 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

Drug: 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

Drug: Prednisone
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 Drug: 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

Drug: 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 Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Radiological Progression-free Survival (rPFS) [ Time Frame: From randomization to radiological disease progression or death from any cause, up to 30 months ]
  2. Time to Radiological Bone Progression by Treatment Group [ Time Frame: From randomization to radiological bone progression up to 30 months ]
  3. Symptomatic Skeletal Event-free Survival (SSE-FS) [ Time Frame: From randomization to the earlier SSE or death, up to 30 months ]
  4. Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: From randomization to first SSE or death, up to 30 months ]
  5. Overall Survival (OS) [ Time Frame: From randomization to the date of radiological disease progression, up to 7.5 years ]


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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
  • 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

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): NCT02034552


  Show 19 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02034552     History of Changes
Other Study ID Numbers: 16544
First Posted: January 13, 2014    Key Record Dates
Results First Posted: July 2, 2017
Last Update Posted: October 26, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Radium Ra 223 dichloride
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors