Clinical trial NCT00617669: A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer
Official title: A Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 (Zibotentan) in Combination With Docetaxel in Comparison With Docetaxel in Patients With Metastatic Hormone-resistant Prostate Cancer
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: 2008-02-18
Enrollment: 1494
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 M1C is a large phase III clinical trial studying the safety and efficacy of ZD4054 (Zibotentan) in combination with docetaxel (Taxotere) in patients with metastatic hormone resistant prostate cancer (HRPC).

This clinical trial will test if the Endothelin A Receptor Antagonist ZD4054 (Zibotentan) can further improve survival compared with docetaxel alone.

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 compared with docetaxel.

All patients participating in this clinical trial will receive docetaxel chemotherapy, which is a commonly used chemotherapy to treat prostate cancer in addition to other existing prostate cancer therapies.

Half the patients will receive ZD4054 (Zibotentan), and half the patients will receive placebo in addition to docetaxel and other prostate cancer therapy. By participating in this trial there is a 50% chance that patients will receive an agent that may further 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.

* Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has spread to the bone (bone metastasis)
* Increasing Prostate Specific Antigen (PSA), collected within one year of enrollment
* Currently receiving treatment with surgical or medical castration

Exclusion Criteria:

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

* Previous treatment with chemotherapy (paclitaxel, docetaxel, and mitoxantrone). Prior targeted cancer therapies are permitted if received during a previous clinical trial.
* Suffering from heart failure or had a myocardial infarction within last 6 months
* A history of epilepsy or seizures

Primary outcomes:
measure: Overall Survival
timeFrame: Patients were followed for survival up to 40 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Patients were followed for progression up to 40 months
measure: Incidence of Skeletal Related Events
timeFrame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
measure: Time to Pain Progression
timeFrame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
measure: Pain Response
timeFrame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
measure: Health Related Quality of Life
timeFrame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
measure: PSA Response
timeFrame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Norwich
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Gainsville
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: PORTUGALt St. Lucie
country: United States
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state: Florida
city: Rockville
country: United States
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state: Maryland
city: Minneapolis
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state: Minnesota
city: Lincoln
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state: Nebraska
city: Omaha
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state: Nebraska
city: Chapel Hill
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state: North Carolina
city: Durham
country: United States
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state: North Carolina
city: Winston-Salem
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state: North Carolina
city: Canton
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state: Ohio
city: Cincinnati
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city: Pittsburgh
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state: Pennsylvania
city: Charleston
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state: South Carolina
city: Chattanooga
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city: Nashville
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city: San Antonio
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state: Texas
city: Richmond
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city: Seattle
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city: Milwaukee
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state: Wisconsin
city: Bahia Blanca
country: Argentina
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state: Buenos Aires
city: Buenos Aires
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state: New South Wales
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city: Redcliffe
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city: Ashford
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state: CZECHOSLOVAKIA Republic
city: Jablonec nad Nisou
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city: Prague 2
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city: Prague 6
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city: Usti nad Labem
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state: FRANCEnce
city: Paris
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city: Saint Herblain
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city: Hannover
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state: GERMANYmany
city: Berlin
country: Germany
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city: Bonn
country: Germany
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city: Dresden
country: Germany
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city: Emmendingen
country: Germany
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city: Kirchheim-Teck
country: Germany
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city: Leipzig
country: Germany
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city: Luebeck
country: Germany
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city: Muenster
country: Germany
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city: Tuebingen
country: Germany
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city: Wuppertal
country: Germany
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city: Budapest
country: Hungary
facility: Research Site
state: HUNGARYary
city: Gyor
country: Hungary
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city: Miskolc
country: Hungary
facility: Research Site
state: HUNGARYary
city: Ny Regyh Za
country: Hungary
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state: HUNGARYary
city: Szeged
country: Hungary
facility: Research Site
state: HUNGARYary
city: Bangalore
country: India
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state: Karnataka
city: Trivandrum
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state: Kerala
city: Bhopal
country: India
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state: Madhya Pradesh
city: Pune
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state: Maharashtra
city: Bikaner
country: India
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state: Rajasthan
city: Jaipur
country: India
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state: Rajasthan
city: Vellore
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state: Tamil Nadu
city: Kolkata
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state: West Bengal
city: Kolkota
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country: India
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city: Genoa
country: Italy
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city: Lugo (RA)
country: Italy
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city: Rome
country: Italy
facility: Research Site
city: Cheongju
country: Korea, Republic of
facility: Research Site
state: Chungbuk
city: Ilsandong-gu, Goyang-si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Nowon-gu
country: Korea, Republic of
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state: Seoul
city: Seodaemun-gu
country: Korea, Republic of
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city: Songpa-gu
country: Korea, Republic of
facility: Research Site
state: Seoul
city: Nijmegen
country: Netherlands
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city: Cercado de Arequipa
country: Peru
facility: Research Site
state: Arequipa
city: Cercado
country: Peru
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state: Arequipa
city: Callao
country: Peru
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city: Lima
country: Peru
facility: Research Site
city: Lublin
country: Poland
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state: POLANDand
city: Swidnica
country: Poland
facility: Research Site
state: POLANDand
city: Warszaa
country: Poland
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state: POLANDand
city: Koscierzyna
country: Poland
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city: Wroclaw
country: Poland
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
state: PORTUGALtugal
city: PORTUGALto
country: Portugal
facility: Research Site
state: PORTUGALtugal
city: Bucharest
country: Romania
facility: Research Site
city: Sibiu
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Barnaul
country: Russian Federation
facility: Research Site
state: RUSSIAsia
city: Izhevsk
country: Russian Federation
facility: Research Site
state: RUSSIAsia
city: Kursk
country: Russian Federation
facility: Research Site
state: RUSSIAsia
city: Sochi
country: Russian Federation
facility: Research Site
state: RUSSIAsia
city: Voronezh
country: Russian Federation
facility: Research Site
state: RUSSIAsia
city: Belgrade
country: Serbia
facility: Research Site
state: SERBIAbia
city: Beograd
country: Serbia
facility: Research Site
state: SERBIAbia
city: Nis
country: Serbia
facility: Research Site
state: SERBIAbia
city: Panorama
country: South Africa
facility: Research Site
state: Cape Town
city: TyGERberg
country: South Africa
facility: Research Site
state: Cape Town
city: Overport
country: South Africa
facility: Research Site
state: Durban
city: Bloemfontein
country: South Africa
facility: Research Site
city: PORt Elizabeth
country: South Africa
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Aarau
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
state: TAIWANwan
city: TAIWANpei
country: Taiwan
facility: Research Site
state: TAIWANwan
city: Reading
country: United Kingdom
facility: Research Site
state: Berkshire
city: Westgate Road
country: United Kingdom
facility: Research Site
state: Newcastle Upon Tyne
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Karim Fizazi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Judd W Moul, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fizazi K, Higano CS, Nelson JB, Gleave M, Miller K, Morris T, Nathan FE, McIntosh S, Pemberton K, Moul JW. Phase III, randomized, placebo-controlled study of docetaxel in combination with zibotentan in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2013 May 10;31(14):1740-7. doi: 10.1200/JCO.2012.46.4149. Epub 2013 Apr 8.