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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02043678




Registration number
NCT02043678
Ethics application status
Date submitted
21/01/2014
Date registered
23/01/2014
Date last updated
26/02/2024

Titles & IDs
Public title
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
Scientific 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)
Secondary ID [1] 0 0
2013-003438-33
Secondary ID [2] 0 0
15396
Universal Trial Number (UTN)
Trial acronym
ERA 223
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Radium-223 dichloride (Xofigo, BAY88-8223)
Treatment: Drugs - Matching placebo (normal saline)
Treatment: Drugs - Abiraterone
Treatment: Drugs - Prednisone/Prednisolone

Experimental: Radium-223 dichloride + Abi/Pred - Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology \[NIST\] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met)

Placebo comparator: Placebo + Abi/Pred - Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met)


Treatment: Drugs: Radium-223 dichloride (Xofigo, BAY88-8223)
50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of NIST update) body weight, intravenous injection (IV-slow bolus), every 4 weeks for 6 cycles

Treatment: Drugs: Matching placebo (normal saline)
Intravenous injection ( IV-slow bolus), every 4 weeks for 6 cycles

Treatment: Drugs: Abiraterone
1000 mg once daily, oral, with best supportive care

Treatment: Drugs: Prednisone/Prednisolone
5 mg twice daily, oral, with best supportive care
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Symptomatic Skeletal Event Free Survival (SSE-FS)
Timepoint [1] 0 0
From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization until death from any cause, up to 67 months
Secondary outcome [2] 0 0
Radiological Progression Free Survival (rPFS)
Timepoint [2] 0 0
From randomization until the date of confirmed radiological progression or death, up to 47 months
Secondary outcome [3] 0 0
Time to Pain Progression
Timepoint [3] 0 0
From randomization until the date of pain progression based on pain score, up to 47 months
Secondary outcome [4] 0 0
Time to Cytotoxic Chemotherapy
Timepoint [4] 0 0
From randomization until the date of first cytotoxic chemotherapy, up to 47 months
Secondary outcome [5] 0 0
Time to Opiate Use for Cancer Pain
Timepoint [5] 0 0
From randomization until the date of opiate use, up to 47 months
Secondary outcome [6] 0 0
Number of Participants With Treatment-emergent Adverse Events
Timepoint [6] 0 0
From start of study treatment until the end of the treatment period, up to 65 months
Secondary outcome [7] 0 0
Number of Subjects With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity
Timepoint [7] 0 0
From start of study treatment until the end of the treatment period, up to 65 months
Secondary outcome [8] 0 0
Number of Participants With Any Treatment-emergent Additional Primary Malignancies
Timepoint [8] 0 0
From start of study treatment until 4 weeks after last study treatment, up to 65 months
Secondary outcome [9] 0 0
Number of Participants With Treatment-emergent Bone Fractures
Timepoint [9] 0 0
From start of study treatment until 4 weeks after last study treatment, up to 65 months
Secondary outcome [10] 0 0
Number of Participants With Post-treatment Adverse Events
Timepoint [10] 0 0
After the treatment period, up to 46 months
Secondary outcome [11] 0 0
Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity
Timepoint [11] 0 0
After the treatment period, up to 46 months
Secondary outcome [12] 0 0
Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders
Timepoint [12] 0 0
After the treatment period, up to 46 months
Secondary outcome [13] 0 0
Number of Participants With Post-treatment Bone Fractures
Timepoint [13] 0 0
After the treatment period, up to 46 months

Eligibility
Key inclusion criteria
* Histologically confirmed adenocarcinoma of the prostate
* Male subjects of age = 18 years
* Prostate cancer progression documented by prostate specific antigen (PSA) 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 progression after discontinuing the anti-androgen prior to enrollment
* Maintenance of medical castration or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L)
* Eastern Cooperative Oncology Group performance status (ECOG PS) score 0 or 1
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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 twice daily
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/02/2024
Sample size
Target
Accrual to date
Final
806
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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- St Leonards
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- Adelaide
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- East Bentleigh
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- Fitzroy
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- Heidelberg
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- Darlinghurst
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- East Melbourne
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- Randwick
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2065 - St Leonards
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5000 - Adelaide
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3165 - East Bentleigh
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3065 - Fitzroy
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3084 - Heidelberg
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2010 - Darlinghurst
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3002 - East Melbourne
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2031 - Randwick
Recruitment outside Australia
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Romford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Janssen Research & Development, LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02043678
Trial related presentations / publications
Smith M, Parker C, Saad F, Miller K, Tombal B, Ng QS, Boegemann M, Matveev V, Piulats JM, Zucca LE, Karyakin O, Kimura G, Matsubara N, Nahas WC, Nole F, Rosenbaum E, Heidenreich A, Kakehi Y, Zhang A, Krissel H, Teufel M, Shen J, Wagner V, Higano C. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):408-419. doi: 10.1016/S1470-2045(18)30860-X. Epub 2019 Feb 6. Erratum In: Lancet Oncol. 2019 Oct;20(10):e559. doi: 10.1016/S1470-2045(19)30587-X.
Shore N, Higano CS, George DJ, Sternberg CN, Saad F, Tombal B, Miller K, Kalinovsky J, Jiao X, Tangirala K, Sartor O. Concurrent or layered treatment with radium-223 and enzalutamide or abiraterone/prednisone: real-world clinical outcomes in patients with metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2020 Dec;23(4):680-688. doi: 10.1038/s41391-020-0236-0. Epub 2020 May 13.
Matsubara N, Kimura G, Uemura H, Uemura H, Nakamura M, Nagamori S, Mizokami A, Kikukawa H, Hosono M, Kinuya S, Krissel H, Siegel J, Kakehi Y. A randomized, double-blind, comparison of radium-223 and placebo, in combination with abiraterone acetate and prednisolone, in castration-resistant metastatic prostate cancer: subgroup analysis of Japanese patients in the ERA 223 study. Int J Clin Oncol. 2020 Apr;25(4):720-731. doi: 10.1007/s10147-019-01589-6. Epub 2019 Dec 10.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02043678