check_circleStudy Completed

Prostatic Neoplasms

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

Trial purpose

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.

Key Participants Requirements

Sex

Male

Age

18 - N/A
  • - 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
  • - 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.

Trial summary

Enrollment Goal
806
Trial Dates
March 2014 - February 2024
Phase
Phase 3
Could I Receive a placebo
No
Products
Xofigo (Radium-223 dichloride, BAY88-8223)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Kfar Saba, 4428164, Israel
Completed
Haifa, 3109601, Israel
Completed
Petach Tikva, 4941492, Israel
Completed
Jerusalem, 9112001, Israel
Completed
Tel Aviv, 6423906, Israel
Completed
Beer Sheva, 8410101, Israel
Completed
Ramat Gan, 5262000, Israel
Completed
Kuopio, FIN- 70029, Finland
Completed
Seinäjoki, 60220, Finland
Completed
Helsinki, 00029, Finland
Completed
Tampere, 33520, Finland
Completed
Berlin, 12203, Germany
Completed
Sutton, SM2 5PT, United Kingdom
Completed
BRUXELLES - BRUSSEL, 1200, Belgium
Completed
GENT, 9000, Belgium
Completed
EDEGEM, 2650, Belgium
Completed
Romford, RM7 0AG, United Kingdom
Completed
Bebington, CH63 4JY, United Kingdom
Completed
Northwood, HA6 2VR, United Kingdom
Completed
Coventry, CV2 2DX, United Kingdom
Completed
Madrid, 28009, Spain
Completed
Barcelona, 08035, Spain
Completed
Oviedo, 33011, Spain
Completed
Hospitalet de Llobregat, 08907, Spain
Completed
Barcelona, 8036, Spain
Completed
Madrid, 28046, Spain
Completed
Pamplona, 31008, Spain
Completed
Madrid, 28034, Spain
Completed
Madrid, 28033, Spain
Completed
Pamplona, 31008, Spain
Completed
Badalona, 8916, Spain
Completed
Umea, 901 85, Sweden
Completed
New Orleans, 70112, United States
Completed
Bodø, 8092, Norway
Completed
Lørenskog, 1478, Norway
Completed
Oslo, 450, Norway
Completed
Baltimore, 21201, United States
Completed
Detroit, 48202, United States
Withdrawn
Scottsdale, 85260, United States
Withdrawn
Raleigh, 27607, United States
Completed
Seattle, 98109-1023, United States
Completed
Rockville, 20850, United States
Completed
PARIS, 75010, France
Completed
PARIS, 75005, France
Withdrawn
grenoble, 38700, France
Completed
BESANCON, 25030, France
Withdrawn
LILLE CEDEX, 59020, France
Completed
Bordeaux Cedex, 33076, France
Withdrawn
CAEN CEDEX 5, 14076, France
Completed
TOULOUSE CEDEX 9, 31059, France
Completed
Sundsvall, 851 86, Sweden
Completed
Stockholm, 171 76, Sweden
Withdrawn
Aachen, 52074, Germany
Terminated
Ulm, 89075, Germany
Completed
München, 81675, Germany
Completed
Dresden, 1307, Germany
Completed
Marburg, 35033, Germany
Completed
Pittsburgh, 15219, United States
Completed
Gdansk, 80-214, Poland
Completed
Gdynia, 81-519, Poland
Withdrawn
Warszawa, 02-781, Poland
Completed
Gliwice, 44-101, Poland
Completed
Cortona, 52040, Italy
Completed
Genova, 16128, Italy
Completed
Växjö, 351 85, Sweden
Completed
Atlanta, 30322, United States
Withdrawn
Newark, 19718, United States
Completed
ZWOLLE, 8025 AB, Netherlands
Completed
AMSTERDAM, 1105 AZ, Netherlands
Completed
Fitzroy, 3065, Australia
Completed
Sydney, 2010, Australia
Completed
Adelaide, 5000, Australia
Withdrawn
Birmingham, 35294-7201, United States
Completed
Ottawa, K1H 8L6, Canada
Completed
Belo Horizonte, 30130-090, Brazil
Completed
Boston, 02114-2696, United States
Completed
São Paulo, 01246-000, Brazil
Completed
Zerifin, 7030000, Israel
Completed
East Melbourne, 3002, Australia
Completed
Leeds, LS9 7TF, United Kingdom
Completed
Belfast, BT9 7AB, United Kingdom
Completed
Guildford, GU2 7XX, United Kingdom
Completed
Milano, 20133, Italy
Withdrawn
Bari, 70124, Italy
Completed
Trento, 38100, Italy
Completed
Vancouver, V5Z 4E6, Canada
Completed
Québec, G1R 2J6, Canada
Withdrawn
Lund, 222 42, Sweden
Completed
Fort Myers, 33905, United States
Withdrawn
Indianapolis, 46202, United States
Withdrawn
Bethesda, 20889-5600, United States
Withdrawn
Palermo, 90146, Italy
Completed
Roma, 152, Italy
Completed
Cagliari, 9125, Italy
Completed
NIJMEGEN, 6525 GA, Netherlands
Withdrawn
AMSTERDAM, 1081 HV, Netherlands
Completed
Obninsk, 249036, Russia
Completed
Washington, 20007-2113, United States
Completed
Barretos/SP, 14784-400, Brazil
Completed
Singapore, 168583, Singapore
Completed
Singapore, 258499, Singapore
Completed
Singapore, 119074, Singapore
Withdrawn
Erlangen, 91054, Germany
Withdrawn
Mainz, 55101, Germany
Completed
Jena, 07747, Germany
Withdrawn
Bremen, 28277, Germany
Withdrawn
Hannover, 30625, Germany
Completed
Porto Alegre, 90020-090, Brazil
Withdrawn
Shreveport, 71103, United States
Completed
Wheeling, 26003, United States
Completed
Spokane, 99208-1129, United States
Completed
Burlington, 1805, United States
Completed
Hackensack, 7601, United States
Completed
Traverse City, 49684, United States
Completed
Modena, 41100, Italy
Withdrawn
Brescia, 25123, Italy
Completed
Roma, 00189, Italy
Completed
Linköping, 581 85, Sweden
Withdrawn
Singapore, 169608, Singapore
Withdrawn
Myrtle Beach, 29577, United States
Completed
Tucson, 85704, United States
Completed
Winnipeg, R3A 1R9, Canada
Completed
Omaha, 68130, United States
Completed
Oceanside, 92056, United States
Completed
Toronto, M4N 3M5, Canada
Completed
Montreal, H2L 4M1, Canada
Withdrawn
Scottsdale, 85251, United States
Withdrawn
Miami, 33136, United States
Completed
Sayama, 589-8511, Japan
Completed
Koto-ku, 135-8550, Japan
Completed
Bunkyo-Ku, 113-0022, Japan
Completed
Sapporo, 003-0804, Japan
Completed
Chiba, 260-8717, Japan
Completed
Shinjuku-ku, 160-8582, Japan
Completed
Kashiwa, 277-8577, Japan
Withdrawn
Suita, 565-0871, Japan
Completed
Sendai, 980-8574, Japan
Completed
Kanazawa, 920-8641, Japan
Completed
Bunkyo-ku, 113-8431, Japan
Completed
Hamamatsu, 431-3192, Japan
Completed
Yokohama, 236-0004, Japan
Completed
Edinburgh, EH4 2XU, United Kingdom
Completed
Hamilton, L8V 5C2, Canada
Completed
Sao Paulo, 01308-050, Brazil
Completed
Pittsburgh, 15240, United States
Withdrawn
New Haven, 06510, United States
Completed
Las Vegas, 89169, United States
Withdrawn
Philadelphia, 19104, United States
Completed
Norfolk, 23502, United States
Completed
Milano, 20141, Italy
Completed
Kumamoto, 860-0008, Japan
Completed
Okayama-city, 700-8558, Japan
Completed
Newcastle Upon Tyne, NE4 6BE, United Kingdom
Withdrawn
Dallas, 75246, United States
Completed
Münster, 48149, Germany
Completed
Moscow, 115478, Russia
Withdrawn
Long Beach, 90806, United States
Completed
Calgary, T2N 4N2, Canada
Completed
Kita-gun, 761-0793, Japan
Completed
Sydney, 2031, Australia
Completed
Bruxelles, 1070, Belgium
Withdrawn
Nedlands, 6009, Australia
Completed
Fukuoka, 812-8582, Japan
Completed
Matsuyama, 791-0280, Japan
Completed
Yokohama, 241-8515, Japan
Completed
Miyazaki, 889-1692, Japan
Withdrawn
Woodville South, 5011, Australia
Completed
Hirosaki, 036-8563, Japan
Completed
Heidelberg, 3084, Australia
Completed
St Leonards, 2065, Australia
Completed
Matsumoto, 390-8621, Japan
Completed
Ube, 755-8505, Japan
Completed
Nagasaki, 852-8501, Japan
Completed
Nagoya, 466-8560, Japan
Withdrawn
Nagoya, 460-0001, Japan
Completed
Fukuoka, 811-1395, Japan
Completed
Poznan, 61-485, Poland
Completed
Kurashiki, 701-0192, Japan
Withdrawn
Bologna, 40138, Italy
Completed
London, NW3 2QG, United Kingdom
Completed
Kobe, 650-0047, Japan
Completed
Chiba-shi, 260-8677, Japan
Completed
Bala Cynwyd, 19004, United States
Withdrawn
San Diego, 92123, United States
Completed
Saint Louis, 63110, United States
Completed
Tsukuba, 305-8576, Japan
Completed
East Bentleigh, 3165, Australia
Withdrawn
West Columbia, 29169, United States
Completed
Towson, 21204, United States
Completed
Poughkeepsie, 12601, United States
Withdrawn
Detroit, 48201, United States
Withdrawn
Omaha, 68130, United States
Withdrawn
Scottsdale, 85251, United States
Withdrawn
Seattle, 98101-2756, United States
Withdrawn
Torrance, 90505, United States
Completed
Jeffersonville, 47130, United States
Withdrawn
Middleburg Heights, 44130, United States
Completed
Denver, 80211, United States
Withdrawn
Meridian, 83642, United States
Completed
POITIERS, 86021, France
Completed
Anchorage, 99503, United States
Withdrawn
Shreveport, 71106, United States
Withdrawn
Aventura, 33180, United States
Withdrawn
Cincinnati, 45212, United States
Withdrawn
Springfield, 97477, United States
Completed
Syracuse, 13210, United States
Withdrawn
Troy, 48084, United States
Withdrawn
Los Angeles, 90095, United States
Withdrawn
Homewood, 35209, United States
Withdrawn
Edison, 8837, United States
Withdrawn
Virginia Beach, 23462, United States
Withdrawn
Salt Lake City, 84106, United States
Withdrawn
Honolulu, 96813, United States
Completed
Sevilla, 41071, Spain
Completed
Madrid, 28050, Spain
Completed
Malaga, 29010, Spain
Completed
Saint-Herblain, 44800, France
Withdrawn
Dallas, 75390, United States
Withdrawn
New York, 10032, United States
Withdrawn
Rochester, 14642, United States
Withdrawn
Chicago, 60612, United States
Withdrawn
Lowell, 01854, United States
Withdrawn
Falls Church, 22031, United States
Withdrawn
Lebanon, 03756, United States
Withdrawn
Sheffield, S10 2SJ, United Kingdom
Completed
Tucson, 85704, United States
Completed
Afula, 1834111, Israel

Primary Outcome

  • 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.
    date_rangeTime Frame:
    From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months
    enhanced_encryption
    Safety Issue:
    Yes

Secondary Outcome

  • Overall Survival (OS)
    OS was defined as the time (months) from the date of randomization to the date of death due to any cause. Participants alive at the survival cut-off date were censored at the last date known to be alive.
    date_rangeTime Frame:
    From randomization until death from any cause, up to 67 months
    enhanced_encryption
    Safety Issue:
    Yes
  • Radiological Progression Free Survival (rPFS)
    rPFS was defined as the time (months) from the date of randomization to the date of confirmed radiological progression or death (if death occurred before progression) based on independent assessment.
    date_rangeTime Frame:
    From randomization until the date of confirmed radiological progression or death, up to 47 months
    enhanced_encryption
    Safety Issue:
    Yes
  • Time to Pain Progression
    Time to pain progression was defined as the interval from randomization to the first date a participant experienced pain progression assessed by Brief Pain Inventory-Short Form and defined as: an increase of 2 or more points in the average worst pain score (WPS) from baseline observed at 2 consecutive evaluations ≥4 weeks apart or initiation of short- or long-acting opioid use for pain for participants with WPS 0 at baseline; an increase of 2 or more points in the average WPS from baseline observed at 2 consecutive evaluations ≥4 weeks apart and an average WPS of ≥4 OR initiation of short- or long-acting opioid use for pain for participants with WPS 1 to 3 at baseline. Participants without pain progression at end of study are censored at the last date known to have not progressed: last evaluation date for pain scores or last visit when recorded opiate use, whichever is last. Participants with no on-study assessment or no baseline assessment are censored at the date of randomization.
    date_rangeTime Frame:
    From randomization until the date of pain progression based on pain score, up to 47 months
    enhanced_encryption
    Safety Issue:
    Yes
  • Time to Cytotoxic Chemotherapy
    Time to cytotoxic chemotherapy is time (months) from randomization to the earliest date of the first cytotoxic chemotherapy. Participants who have not started cytotoxic chemotherapy during the study were censored at the last assessment date.
    date_rangeTime Frame:
    From randomization until the date of first cytotoxic chemotherapy, up to 47 months
    enhanced_encryption
    Safety Issue:
    Yes
  • Time to Opiate Use for Cancer Pain
    Time to opiate use for cancer pain was defined as the interval from the date of randomization to the date of opiate use.
    date_rangeTime Frame:
    From randomization until the date of opiate use, up to 47 months
    enhanced_encryption
    Safety Issue:
    Yes
  • Number of participants with treatment-emergent adverse events
    An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was life-threatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. A treatment-emergent AEs (TEAEs) or serious TEAEs was defined as any event that started on or after the first dose of the study treatment and during the treatment period and was not a continuation of a pretreatment event or started before the first dose and worsened after the first dose or the treatment period. Drug-related TEAEs or serious TEAEs were those with "reasonable causal relationship" to the study treatment decided by the investigators.
    date_rangeTime Frame:
    From start of study treatment until the end of the treatment period, up to 110 months
  • Number of participants with radium-223/placebo-related treatment-emergent adverse events per maximum intensity
    An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. A treatment-emergent AEs (TEAEs) or serious TEAEs was defined as any event that started on or after the first dose of the study treatment and during the treatment period and was not a continuation of a pretreatment event or started before the first dose and worsened after the first dose or the treatment period. Radium-223/placebo-related TEAEs or serious TEAEs were those with "reasonable causal relationship" to radium-223 or placebo decided by the investigators.
    date_rangeTime Frame:
    From start of study treatment until the end of the treatment period, up to 110 months
  • Number of participants with any treatment-emergent additional primary malignancies
    Treatment-emergent additional primary malignancies were adverse events identified as additional primary malignancies that occurred after start of study treatment until the end of the treatment period.
    date_rangeTime Frame:
    From start of study treatment until the end of the treatment period, up to 110 months
  • Number of participants with treatment-emergent bone fractures
    Treatment-emergent fractures were adverse events identified as fractures that occurred after start of study treatment until the end of the treatment period. All bone fractures and bone-associated events (e.g., osteoporosis) were reported as either AEs, or SAEs if the criteria of SAE were met, regardless of the investigator’s causality assessment.
    date_rangeTime Frame:
    From start of study treatment until the end of the treatment period, up to 110 months
  • Number of participants with post-treatment adverse events
    An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs that started after the treatment period were defined as post-treatment AEs. Drug-related AEs were those with "reasonable causal relationship" to the study treatment decided by the investigators.
    date_rangeTime Frame:
    After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up
  • Number of participants with any study drug-related post-treatment adverse events per maximum intensity
    An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs that started after the treatment period were defined as post-treatment AEs. Drug-related AEs were those with "reasonable causal relationship" to the study treatment decided by the investigators.
    date_rangeTime Frame:
    After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up
  • Number of participants with post-treatment additional primary malignancies
    Post-treatment additional primary malignancies were adverse events identified as additional primary malignancies that started after the treatment period.
    date_rangeTime Frame:
    After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up
  • Number of participants with post-treatment chemotherapy-related blood and lymphatic system disorders
    Post-treatment blood and lymphatic system disorders were adverse events identified as blood and lymphatic system disorders that occurred after the end of the treatment period until participant died, was lost to follow-up, withdrew informed consent, actively objected to collection of further data, or was transitioned to the extended safety follow-up study.
    date_rangeTime Frame:
    After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up
  • Number of participants with post-treatment bone fractures
    Post-treatment fractures were adverse events identified as fractures that occured after the end of the treatment period until participant died, was lost to follow-up, withdrew informed consent, actively objected to collection of further data, or was transitioned to the extended safety follow-up study. All bone fractures and bone-associated events (e.g., osteoporosis), were reported as either AEs, or SAEs if the criteria of SAE were met, regardless of the investigator’s causality assessment.
    date_rangeTime Frame:
    After the treatment period, up to 48.5 months in active follow-up and 74.9 months in long-term follow-up

Trial design

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)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
2