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Radium-223 Dichloride and Abiraterone Acetate Compared to Placebo and Abiraterone Acetate for Men With Cancer of the Prostate When Medical or Surgical Castration Does Not Work and When the Cancer Has Spread to the Bone, Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms (ERA 223)

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ClinicalTrials.gov Identifier: NCT02043678
Recruitment Status : Active, not recruiting
First Posted : January 23, 2014
Last Update Posted : April 5, 2018
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer

Brief Summary:
To determine if the addition of radium-223 dichloride to standard treatment is able to prolong life and to delay events specific for prostate cancer which has spread to the bone, such as painful fractures or bone pain which needs to be treated with an X-ray machine.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Matching placebo (normal saline) Drug: Abiraterone Drug: Prednisone/Prednisolone Phase 3

Detailed Description:
This study is a phase III multinational, multicenter,randomized, double blind, placebo controlled, study with a randomization allocation ratio of 1:1 (radium-223 dichloride plus abiraterone acetate plus prednisone/prednisolone: placebo plus abiraterone acetate plus prednisone/prednisolone).The study period will consist of screening/randomization, treatment, active follow-up with clinic visits, active follow-up without clinic visits, and long-term follow-up phases. In this study, subjects will receive study treatment (radium-223 dichloride or placebo in addition to abiraterone acetate plus prednisone/prednisolone for the first 6 cycles followed by abiraterone acetate plus prednisone/prednisolone thereafter) until an on-study symptomatic skeletal event (SSE) occurs (or other withdrawal criteria are met). Follow-up will continue for up to 7 years or until the subject dies, is lost to followup, or withdraws informed consent and actively objects to collection of further data.This study will be conducted at approximately 150 investigative study centers and approximately 800 subjects will be enrolled.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 806 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Abiraterone Acetate and Prednisone/Prednisolone in the Treatment of Asymptomatic or Mildly Symptomatic Chemotherapy-naïve Subjects With Bone Predominant Metastatic Castration-resistant Prostate Cancer(CRPC)
Actual Study Start Date : March 30, 2014
Estimated Primary Completion Date : May 15, 2018
Estimated Study Completion Date : December 23, 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Radium-223 dichloride
Radium-223 dichloride +abiraterone+prednisone/prednisolone All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily), oral prednisone/prednisolone (5 mg twice daily), with best supportive care
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
50 kBq/kg body weight, intravenous injection (IV-slow bolus), every 4 weeks for 6 cycles.(nominal change to 55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update)
Drug: Abiraterone
All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily),with best supportive care
Drug: Prednisone/Prednisolone
All study subjects will receive treatment with oral prednisone/prednisolone (5 mg twice daily), with best supportive care
Placebo Comparator: Placebo
Placebo+abiraterone+prednisone/prednisolone All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily), oral prednisone/prednisolone (5 mg twice daily), with best supportive care
Drug: Matching placebo (normal saline)
Intravenous injection ( IV-slow bolus), every 4 weeks for 6 cycles
Drug: Abiraterone
All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily),with best supportive care
Drug: Prednisone/Prednisolone
All study subjects will receive treatment with oral prednisone/prednisolone (5 mg twice daily), with best supportive care



Primary Outcome Measures :
  1. Symptomatic skeletal event free survival (SSE-FS). [ Time Frame: At 4 years ]

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: At 4 years for interim and at 6 years for final. ]
  2. Time to opiate use for cancer pain [ Time Frame: At 4 years ]
  3. Time to pain progression [ Time Frame: At 4 years ]
  4. Time to cytotoxic chemotherapy [ Time Frame: At 4 years ]
  5. Radiological progression free survival (rPFS) [ Time Frame: At 4 years ]
  6. Number of participants with adverse events as a measure of safety and tolerability. [ Time Frame: Up to 4 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate
  • Male subjects of age ≥ 18 years
  • Prostate cancer progression documented by prostate specific antigen according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
  • Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis.
  • Asymptomatic or mildly symptomatic prostate cancer.
  • Subjects who received combined androgen blockade with an anti-androgen must have shown PSA(prostate specific antigen) progression after discontinuing the anti-androgen prior to enrollment.
  • Medical or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

Exclusion Criteria:

  • Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine
  • Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone bid.
  • Pathological finding consistent with small cell carcinoma of the prostate
  • History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations
  • History of or known brain metastasis.
  • Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.
  • Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization
  • Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered
  • Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime during the 4- week period prior to randomization.

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): NCT02043678


  Show 169 Study Locations
Sponsors and Collaborators
Bayer
Janssen Research & Development, LLC
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02043678     History of Changes
Other Study ID Numbers: 15396
2013-003438-33 ( EudraCT Number )
First Posted: January 23, 2014    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: March 2018

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

Keywords provided by Bayer:
Phase III
Radium-223 dichloride
Abiraterone acetate
Combination therapy
Chemotherapy-naive
Bone metastasis
Castration-resistant prostate cancer (CRPC)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisone
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
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
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents