Study Completed

Prostatic Neoplasms

Bayer Identifier:

15396

ClinicalTrials.gov Identifier:

NCT02043678

EudraCT Number:

2013-003438-33

EU CT Number:

Not Available

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

Trial summary

Enrollment Goal

806

Trial Dates

March 2014 - February 2024

Phase

Phase 3

Could I Receive a placebo

Products

Xofigo (Radium-223 dichloride, BAY88-8223)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
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Withdrawn		Scottsdale, 85260, United States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.
Time Frame:
From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months
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.
Time Frame:
From randomization until death from any cause, up to 67 months
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.
Time Frame:
From randomization until the date of confirmed radiological progression or death, up to 47 months
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.
Time Frame:
From randomization until the date of pain progression based on pain score, up to 47 months
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.
Time Frame:
From randomization until the date of first cytotoxic chemotherapy, up to 47 months
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.
Time Frame:
From randomization until the date of opiate use, up to 47 months
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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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

Additional Information

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