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
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)
2 other identifiers
interventional
806
19 countries
163
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2014
Longer than P75 for phase_3
163 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 21, 2014
CompletedFirst Posted
Study publicly available on registry
January 23, 2014
CompletedStudy Start
First participant enrolled
March 30, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2018
CompletedResults Posted
Study results publicly available
March 5, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
February 8, 2024
CompletedFebruary 19, 2025
January 1, 2025
3.9 years
January 21, 2014
February 12, 2019
January 30, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Symptomatic Skeletal Event Free Survival (SSE-FS)
SSE-FS was defined as time (months) from randomization to the earliest of onset date of skeletal symptoms treated with external beam radiotherapy (EBRT), onset date of pathological bone fracture, onset date of spinal cord compression, procedure date of tumor-related orthopedic surgery, or death from any cause. Participants who died without prior SSE and ≥ 13 weeks after the last SSE assessment are censored at the last SSE assessment date. Participants alive at the survival cut-off date are censored at the last date known to be alive. Participants with multiple events are only counted for the category in which the first event occurred. If multiple SSE (component events) occur on the same date for 1 participant, the participant is only counted into 1 category in the order of: spinal cord compression \> bone fracture \> orthopedic surgery \> EBRT.
From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months
Secondary Outcomes (14)
Overall Survival (OS)
From randomization until death from any cause, up to 67 months
Radiological Progression Free Survival (rPFS)
From randomization until the date of confirmed radiological progression or death, up to 47 months
Time to Pain Progression
From randomization until the date of pain progression based on pain score, up to 47 months
Time to Cytotoxic Chemotherapy
From randomization until the date of first cytotoxic chemotherapy, up to 47 months
Time to Opiate Use for Cancer Pain
From randomization until the date of opiate use, up to 47 months
- +9 more secondary outcomes
Study Arms (2)
Radium-223 dichloride + Abi/Pred
EXPERIMENTALParticipants 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 + Abi/Pred
PLACEBO COMPARATORParticipants 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)
Interventions
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
Intravenous injection ( IV-slow bolus), every 4 weeks for 6 cycles
1000 mg once daily, oral, with best supportive care
5 mg twice daily, oral, with best supportive care
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
- Janssen Research & Development, LLCcollaborator
Study Sites (163)
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Anchorage, Alaska, 99503, United States
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Tucson, Arizona, 85718, United States
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Oceanside, California, 92056, United States
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Denver, Colorado, 80211, United States
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Washington D.C., District of Columbia, 20007-2113, United States
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Fort Myers, Florida, 33901, United States
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Atlanta, Georgia, 30322, United States
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Jeffersonville, Indiana, 47130, United States
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New Orleans, Louisiana, 70112, United States
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Baltimore, Maryland, 21201, United States
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Rockville, Maryland, 20850, United States
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Towson, Maryland, 21204, United States
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Boston, Massachusetts, 02114-2696, United States
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Burlington, Massachusetts, 1805, United States
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Detroit, Michigan, 48202, United States
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Traverse City, Michigan, 49684, United States
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St Louis, Missouri, 63110, United States
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Omaha, Nebraska, 68130, United States
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Las Vegas, Nevada, 89169, United States
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Hackensack, New Jersey, 7601, United States
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Poughkeepsie, New York, 12601, United States
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Syracuse, New York, 13210, United States
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Bala-Cynwyd, Pennsylvania, 19004, United States
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Pittsburgh, Pennsylvania, 15215, United States
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Pittsburgh, Pennsylvania, 15240, United States
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Norfolk, Virginia, 23502, United States
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Seattle, Washington, 98109-1023, United States
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Spokane, Washington, 99208-1129, United States
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Wheeling, West Virginia, 26003, United States
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St Leonards, New South Wales, 2065, Australia
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Sydney, New South Wales, 2010, Australia
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Adelaide, South Australia, 5000, Australia
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East Bentleigh, Victoria, 3165, Australia
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Fitzroy, Victoria, 3065, Australia
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Heidelberg, Victoria, 3084, Australia
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East Melbourne, 3002, Australia
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Randwick, 2031, Australia
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Brussels, 1070, Belgium
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Bruxelles - Brussel, 1200, Belgium
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Edegem, 2650, Belgium
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Ghent, 9000, Belgium
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Belo Horizonte, Minas Gerais, 30130-090, Brazil
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Porto Alegre, Rio Grande do Sul, 90020-090, Brazil
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Barretos/SP, São Paulo, 14784-400, Brazil
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São Paulo, São Paulo, 01246-000, Brazil
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São Paulo, 01409-000, Brazil
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Calgary, Alberta, T2N 4N2, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Winnipeg, Manitoba, R3A 1R9, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Montreal, Quebec, H2L 4M1, Canada
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Québec, Quebec, G1R 2J6, Canada
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Helsinki, FIN-00260, Finland
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Kuopio, FIN- 70029, Finland
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Seinäjoki, 60220, Finland
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Tampere, 33520, Finland
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Besançon, 25030, France
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Bordeaux, 33076, France
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Paris, 75005, France
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Paris, 75010, France
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Poitiers, 86021, France
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Saint-Herblain, 44800, France
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Toulouse, 31059, France
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Ulm, Baden-Wurttemberg, 89075, Germany
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München, Bavaria, 81675, Germany
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Marburg, Hesse, 35033, Germany
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Münster, North Rhine-Westphalia, 48149, Germany
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Dresden, Saxony, 1307, Germany
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Jena, Thuringia, 7747, Germany
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Berlin, 12203, Germany
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Afula, 1834111, Israel
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Beersheba, 8410101, Israel
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Haifa, 3109601, Israel
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Jerusalem, 9112001, Israel
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Kfar Saba, 4428164, Israel
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Petah Tikva, 4941492, Israel
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Ramat Gan, 5262000, Israel
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Tel Aviv, 6423906, Israel
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Ẕerifin, 7030000, Israel
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Modena, Emilia-Romagna, 41100, Italy
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Rome, Lazio, 152, Italy
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Rome, Lazio, 189, Italy
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Genoa, Liguria, 16128, Italy
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Milan, Lombardy, 20133, Italy
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Milan, Lombardy, 20141, Italy
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Cagliari, Sardinia, 9125, Italy
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Trento, Trentino-Alto Adige, 38100, Italy
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Cortona, Tuscany, 52040, Italy
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Nagoya, Aichi-ken, 466-8560, Japan
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Hirosaki, Aomori, 036-8563, Japan
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Chiba, Chiba, 260-8677, Japan
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Kashiwa, Chiba, 277-8577, Japan
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Matsuyama, Ehime, 791-0280, Japan
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Sapporo, Hokkaido, 003-0804, Japan
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Kobe, Hyōgo, 650-0047, Japan
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Tsukuba, Ibaraki, 305-8576, Japan
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Kanazawa, Ishikawa-ken, 920-8641, Japan
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Kita-gun, Kagawa-ken, 761-0793, Japan
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Yokohama, Kanagawa, 236-0004, Japan
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Yokohama, Kanagawa, 241-8515, Japan
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Sendai, Miyagi, 980-8574, Japan
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Matsumoto, Nagano, 390-8621, Japan
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Kurashiki, Okayama-ken, 701-0192, Japan
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Okayama, Okayama-ken, 700-8558, Japan
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Sayama, Osaka, 589-8511, Japan
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Hamamatsu, Shizuoka, 431-3192, Japan
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Bunkyo-Ku, Tokyo, 113-0022, Japan
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Bunkyo-ku, Tokyo, 113-8431, Japan
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Koto-ku, Tokyo, 135-8550, Japan
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Shinjuku-ku, Tokyo, 160-8582, Japan
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Ube, Yamaguchi, 755-8505, Japan
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Chiba, 260-8717, Japan
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Fukuoka, 811-1395, Japan
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Fukuoka, 812-8582, Japan
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Kumamoto, 860-0008, Japan
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Miyazaki, 889-1692, Japan
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Nagasaki, 852-8501, Japan
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Amsterdam, 1105 AZ, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Zwolle, 8025 AB, Netherlands
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Bodø, 8092, Norway
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Lørenskog, 1478, Norway
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Oslo, 450, Norway
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Gdansk, 80-214, Poland
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Gdynia, 81-519, Poland
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Gliwice, 44-101, Poland
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Poznan, 61-485, Poland
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Moscow, 115478, Russia
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Obninsk, 249036, Russia
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Singapore, 119074, Singapore
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Singapore, 168583, Singapore
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Singapore, 258499, Singapore
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Badalona, Barcelona, 8916, Spain
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L'Hospitalet de Llobregat, Barcelona, 08907, Spain
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Málaga, Málaga, 29010, Spain
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Oviedo, Principality of Asturias, 33011, Spain
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Barcelona, 08035, Spain
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Barcelona, 8036, Spain
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Madrid, 28009, Spain
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Madrid, 28033, Spain
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Madrid, 28034, Spain
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Madrid, 28046, Spain
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Madrid, 28050, Spain
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Pamplona, 31008, Spain
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Seville, 41071, Spain
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Linköping, 581 85, Sweden
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Stockholm, 171 76, Sweden
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Sundsvall, 851 86, Sweden
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Umeå, 901 85, Sweden
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Vaxjo, 351 85, Sweden
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Edinburgh, Lothian, EH4 2XU, United Kingdom
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Bebington, Merseyside, CH63 4JY, United Kingdom
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Northwood, Middlesex, HA6 2VR, United Kingdom
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Guildford, Surrey, GU2 7XX, United Kingdom
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Sutton, Surrey, SM2 5PT, United Kingdom
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Newcastle upon Tyne, Tyne and Wear, NE4 6BE, United Kingdom
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Coventry, West Midlands, CV2 2DX, United Kingdom
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Belfast, BT9 7AB, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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London, NW3 2QG, United Kingdom
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Romford, RM7 0AG, United Kingdom
Related Publications (3)
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.
PMID: 30738780RESULTShore 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.
PMID: 32404868DERIVEDMatsubara 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.
PMID: 31823152DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
2 participants randomized to the placebo treatment group unintentionally received 1 radium-223 dichloride dose during the treatment period. These 2 participants are summarized in the radium-223 dichloride treatment group in the safety analysis; while were analyzed as randomized, i.e., in the placebo arm for the efficacy analysis.
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- Bayer
Study Officials
- STUDY DIRECTOR
Bayer Study Director
Bayer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 21, 2014
First Posted
January 23, 2014
Study Start
March 30, 2014
Primary Completion
February 15, 2018
Study Completion
February 8, 2024
Last Updated
February 19, 2025
Results First Posted
March 5, 2019
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will not share
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.