Clinical trial NCT00554229: A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Hormone Resistant Prostate Cancer With Bone Metastases
Official title: A Phase III Trial to Test the Efficacy of ZD4054(Zibotentan), an Endothelin A Receptor Antagonist, Versus Placebo in Patients With Hormone Resistant Prostate Cancer (HRPC) and Bone Metastasis Who Are Pain Free and Mildly Symptomatic.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Hormone Resistant Prostate Cancer
Endothelin A Receptor Antagonist
Endothelin A
Endothelin A antagonist
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2007-11-06
Enrollment: 896
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Enthuse M1 is a large phase III clinical trial studying the safety and efficacy of ZD4054 (Zibotentan) in patients with hormone resistant prostate cancer and bone metastases.

* This clinical trial will test if the Endothelin A Receptor Antagonist ZD4054 (Zibotentan) can improve survival compared with placebo.
* ZD4054(Zibotentan) is a new type of agent, which is thought to slow tumour growth and spread by blocking Endothelin A receptor activity. This trial will look at the effects of ZD4054 (Zibotentan) in hormone resistant prostate cancer patients with bone metastases.
* All patients participating in this clinical trial will receive existing standard prostate cancer treatments in addition to trial therapy.
* Half the patients will receive ZD4054 (Zibotentan), and half the patients will receive placebo in addition to standard prostate cancer therapy. By participating in this trial there is a 50% chance that patients will receive an agent that may slow the progression of the tumour.
* No patients will be deprived of standard prostate cancer therapy.


Eligibility criteria: Inclusion Criteria:

Patients who answer TRUE to the following criteria may be eligible to participate in this trial.

1. Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has spread to the bone (bone metastases)
2. Increasing Prostate Specific Antigen (PSA) over a one month period
3. No pain, or mild pain from prostate cancer
4. Currently receiving treatment with surgical or medical castration

Exclusion Criteria:

Patients who answer TRUE to the following may NOT eligible to participate in this trial.

1. Currently using opiates based pain killers)
2. Previous treatment with chemotherapy (paclitaxel, docetaxel, and mitoxantrone)
3. Suffering from heart failure or had a myocardial infarction within last 6 months
4. A history of epilepsy or seizures

Primary outcomes:
measure: Overall Survival
timeFrame: From date of randomization until date of death, assessed up to 32 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 31 months
measure: Time to Use of Opiates
timeFrame: From date of randomization until use of opiates for disease-related symptoms for a duration ≥1 week, assessed up to 31 months
measure: Incidence of Skeletal Related Events
timeFrame: From date of randomization until occurrence of a skeletal related event, assessed up to 31 months
measure: Bone Metastases Formation
timeFrame: Patients were assessed every 12 weeks
measure: Health Related Quality of Life
timeFrame: Patients were assessed at every visit
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: Patients were assessed every 12 weeks
measure: Time to Pain Progression
timeFrame: Patients were assessed every 12 weeks
measure: Time to Initiation of Chemotherapy
timeFrame: Patients were assessed every 12 weeks
measure: Pharmacokinetic Characteristics of ZD4054
timeFrame: PK samples were performed at randomisation, Week 4, Week 8 and Week 12
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Greenbrae
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Palm Springs
country: United States
facility: Research Site
state: California
city: San Mateo
country: United States
facility: Research Site
state: California
city: Norwich
country: United States
facility: Research Site
state: Connecticut
city: Washington
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facility: Research Site
state: District of Columbia
city: Gainsville
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facility: Research Site
state: Florida
city: Port St.Lucie
country: United States
facility: Research Site
state: Florida
city: Des Moines
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facility: Research Site
state: Iowa
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
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state: Tennessee
city: Salt Lake City
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state: Utah
city: Burlington
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facility: Research Site
state: Vermont
city: Norfolk
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facility: Research Site
state: Virginia
city: Seattle
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state: Washington
city: Wheeling
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state: West Virginia
city: Milwaukee
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state: Wisconsin
city: Buenos Aires
country: Argentina
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state: Buenos Aires Province
city: Santa Fe
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city: Hornsby
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state: New South Wales
city: St Leonards
country: Australia
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state: New South Wales
city: Redcliffe
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state: Queensland
city: Ashford
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state: South Australia
city: Subiaco
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state: Western Australia
city: Graz
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city: Wels
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city: Brussels
country: Belgium
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city: Gent
country: Belgium
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city: Kortrijk
country: Belgium
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city: Leuven
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city: Fortaleza
country: Brazil
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state: Ceara
city: Goiania
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state: Goias
city: Belo Horizonte
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state: Minas Gerais
city: Curitiba
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city: Porto Alegre
country: Brazil
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state: Rio Grande do Sul
city: Ribeirao Preto
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city: Santo Andre
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state: Sao Paulo
city: Sao Paulo
country: Brazil
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city: Calgary
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state: Alberta
city: Edmonton
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state: Alberta
city: Vancouver
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state: British Columbia
city: Kentville
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city: Barrie
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state: Ontario
city: Burlington
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state: Ontario
city: Hamilton
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city: Kitchener
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city: London
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city: Mississauga
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city: North York
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city: Oakville
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city: Ottawa
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city: Toronto
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city: Laval
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city: Montreal
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city: Point-Claire
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state: Quebec
city: Quebec City
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state: Quebec
city: Quebec
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city: Haidian District
country: China
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state: Beijing
city: Xi Cheng District
country: China
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state: Beijing
city: Xicheng District
country: China
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state: Beijing
city: Wuhan
country: China
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state: Hubei
city: Nanjing
country: China
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state: Jiangsu
city: Pudong New Area
country: China
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state: Shanghai
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Xuhui District
country: China
facility: Research Site
state: Shanghai
city: Xi'an
country: China
facility: Research Site
state: Shanxi
city: Prague 4
country: Czech Republic
facility: Research Site
state: Prague
city: Prague 6
country: Czech Republic
facility: Research Site
state: Prague
city: Brno
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city: Olomouc
country: Czech Republic
facility: Research Site
city: Usti nad Labem
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city: Aalborg
country: Denmark
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city: Aarhus
country: Denmark
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city: Herlev
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city: Kobenhavn
country: Denmark
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city: Joensuu
country: Finland
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city: Kajaanintie
country: Finland
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city: Tampere
country: Finland
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city: Montpellier
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country: France
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city: Poitiers Cedex
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city: Suresnes
country: France
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city: Toulouse
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city: Villejuif
country: France
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city: Planegg
country: Germany
facility: Research Site
state: Muenchen
city: Kirchheim
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state: Teck
city: Augsburg
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city: Bad Gegeberg
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city: Berlin
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city: Emmendingen
country: Germany
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city: Leipzig
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city: Luebeck
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city: Mannheim
country: Germany
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city: Muenchen
country: Germany
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city: Reutlingen
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city: Hong Kong
country: Hong Kong
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country: Hungary
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city: Rohini
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city: Mumbai
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city: Ludhiana
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city: Kolkota
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city: Milan
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city: Asahi-City
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state: Chiba
city: Chiba-City
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state: Chiba
city: Narashino-city
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state: Chiba
city: Matsuyama-City
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state: Ehime
city: Fukuoka-City
country: Japan
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state: Fukuoka
city: Maebashi-City
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state: Gunma
city: Otake-City
country: Japan
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state: Hiroshima
city: Sapporo-City
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state: Hokkaido
city: Kobe-City
country: Japan
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state: Hyogo
city: Tsukuba-City
country: Japan
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state: Ibaraki
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state: Kagawa
city: Sagamihara-City
country: Japan
facility: Research Site
state: Kanagawa
city: Kyoto-City
country: Japan
facility: Research Site
state: Kyoto
city: Sendai-City
country: Japan
facility: Research Site
state: Miyagi
city: Oita-City
country: Japan
facility: Research Site
state: Oita
city: Osaka-City
country: Japan
facility: Research Site
state: Osaka
city: Osaka-Sayama-City
country: Japan
facility: Research Site
state: Osaka
city: Suita-City
country: Japan
facility: Research Site
state: Osaka
city: Wako-City
country: Japan
facility: Research Site
state: Saitama
city: Hamamatsu-city
country: Japan
facility: Research Site
state: Shizuoka
city: Sunto-gun
country: Japan
facility: Research Site
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Research Site
state: Tokyo
city: Fuchu_city
country: Japan
facility: Research Site
state: Tokyo
city: Itabashi-Ku
country: Japan
facility: Research Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Research Site
state: Tokyo
city: Mitaka-City
country: Japan
facility: Research Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Research Site
state: Tokyo
city: Nagasaki
country: Japan
facility: Research Site
city: Heungduk-gu Cheongju
country: Korea, Republic of
facility: Research Site
state: Chungbuk
city: Seongnam-si
country: Korea, Republic of
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state: Gyeonggi-do
city: Seo-gu
country: Korea, Republic of
facility: Research Site
state: Pusan
city: Gangnam-gu
country: Korea, Republic of
facility: Research Site
state: Seoul
city: Songpa-gu
country: Korea, Republic of
facility: Research Site
state: Seoul
city: Metepec
country: Mexico
facility: Research Site
state: Estado de Mexico
city: Distrito Federal Ciudad
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
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city: Eindhoven
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
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city: Bialystok
country: Poland
facility: Research Site
city: Koscierzyna
country: Poland
facility: Research Site
city: Krakow
country: Poland
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city: Rzeszow
country: Poland
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city: Warszawa
country: Poland
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city: Wroclaw
country: Poland
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city: Coimbra
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Stary Oskol
country: Russian Federation
facility: Research Site
state: Belgorodskaya region
city: Barnaul
country: Russian Federation
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Kursk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Sochi
country: Russian Federation
facility: Research Site
city: St. Petersgurg
country: Russian Federation
facility: Research Site
city: Voronezh
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Novi Sad
country: Serbia
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Tygerberg
country: South Africa
facility: Research Site
state: Cape Town
city: Bloemfontein
country: South Africa
facility: Research Site
city: Pietermaritzburg
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Goteborg
country: Sweden
facility: Research Site
city: Gothenburg
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Locarno
country: Switzerland
facility: Research Site
city: Sursee
country: Switzerland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
state: Berkshire
city: Cambridge
country: United Kingdom
facility: Research Site
state: Cambridgeshire
city: Maidstone
country: United Kingdom
facility: Research Site
state: Kent
city: Huddersfield
country: United Kingdom
facility: Research Site
state: Yorkshire
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: The Prostate Centre at Vancouver General Hospital
name: Martin Gleave, MD, FRCSC, FACS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Joel B Nelson, MD
role: PRINCIPAL_INVESTIGATOR
References: