A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer

Prostate Cancer Clinical Trial

— ENTHUSE M1C  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00617669
• Other study ID #: D4320C00033
• Status: Completed
• Phase: Phase 3
• First received: January 24, 2008
• Last updated: September 4, 2012
• Start date: January 2008
• Est. completion date: July 2011

Study information

• Verified date: April 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1494
• Est. completion date: July 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Docetaxel
intravenous infusion given every three weeks
• ZD4054
10 mg oral once daily dose
• Placebo
placebo oral tablet once daily

Locations

Country	Name	City	State
Argentina	Research Site	Bahia Blanca	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Santa Fe
Australia	Research Site	Ashford	South Australia
Australia	Research Site	Darlinghurst	New South Wales
Australia	Research Site	Footscray	Victoria
Australia	Research Site	Perth	Western Australia
Australia	Research Site	Redcliffe	Queensland
Australia	Research Site	St Leonards	New South Wales
Australia	Research Site	Subiaco	Western Australia
Australia	Research Site	Wodonga	Victoria
Australia	Research Site	Wollongong	New South Wales
Brazil	Research Site	Belo Horizonte	Minas GERMANYais
Brazil	Research Site	Curitiba	Parana/ Brazil
Brazil	Research Site	Fortaleza	Ceara/ LA
Brazil	Research Site	Goiania	Goias/ LA
Brazil	Research Site	Goiania	Goias
Brazil	Research Site	Londrina	PR
Brazil	Research Site	PORTUGALto Alegre	Rio Grande do Sul/ LA
Brazil	Research Site	Ribeirao Preto	Sao Paulo/ LA
Brazil	Research Site	Rio de Janeiro	RJ
Brazil	Research Site	Santo Andre	Sao Paulo
Brazil	Research Site	Sao Paulo
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	London	Ontario
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Winnipeg	Manitoba
Czech Republic	Research Site	Brno	CZECHOSLOVAKIA Republic
Czech Republic	Research Site	Jablonec nad Nisou
Czech Republic	Research Site	Kromeriz
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Prague 2
Czech Republic	Research Site	Prague 6
Czech Republic	Research Site	Usti nad Labem
Finland	Research Site	Helsinki
Finland	Research Site	Joensuu
Finland	Research Site	Seinajoki
France	Research Site	La Roche sur Yon	FRANCEnce
France	Research Site	Marseille	FRANCEnce
France	Research Site	Paris	FRANCEnce
France	Research Site	Paris
France	Research Site	Reims	FRANCEnce
France	Research Site	Saint Herblain
France	Research Site	Villejuif	FRANCEnce
Germany	Research Site	Berlin
Germany	Research Site	Bonn
Germany	Research Site	Dresden
Germany	Research Site	Emmendingen
Germany	Research Site	Hannover	GERMANYmany
Germany	Research Site	Kirchheim-Teck
Germany	Research Site	Leipzig
Germany	Research Site	Luebeck
Germany	Research Site	Muenster
Germany	Research Site	Tuebingen
Germany	Research Site	Wuppertal
Hungary	Research Site	Budapest	HUNGARYary
Hungary	Research Site	Gyor	HUNGARYary
Hungary	Research Site	Miskolc	HUNGARYary
Hungary	Research Site	Ny Regyh Za	HUNGARYary
Hungary	Research Site	Szeged	HUNGARYary
India	Research Site	Bangalore	Karnataka
India	Research Site	Bhopal	Madhya Pradesh
India	Research Site	Bikaner	Rajasthan
India	Research Site	Delhi
India	Research Site	Jaipur	Rajasthan
India	Research Site	Kolkata	West Bengal
India	Research Site	Kolkota	West Bengal
India	Research Site	New Delhi
India	Research Site	Pune	Maharashtra
India	Research Site	Trivandrum	Kerala
India	Research Site	Vellore	Tamil Nadu
Italy	Research Site	Genoa
Italy	Research Site	Lugo (RA)
Italy	Research Site	Rome
Korea, Republic of	Research Site	Cheongju	Chungbuk
Korea, Republic of	Research Site	Ilsandong-gu, Goyang-si	Gyeonggi-do
Korea, Republic of	Research Site	Nowon-gu	Seoul
Korea, Republic of	Research Site	Seodaemun-gu	Seoul
Korea, Republic of	Research Site	Songpa-gu	Seoul
Netherlands	Research Site	Nijmegen
Peru	Research Site	Callao
Peru	Research Site	Cercado	Arequipa
Peru	Research Site	Cercado de Arequipa	Arequipa
Peru	Research Site	Lima
Poland	Research Site	Koscierzyna
Poland	Research Site	Lublin	POLANDand
Poland	Research Site	Swidnica	POLANDand
Poland	Research Site	Warszaa	POLANDand
Poland	Research Site	Wroclaw
Portugal	Research Site	Coimbra	PORTUGALtugal
Portugal	Research Site	PORTUGALto	PORTUGALtugal
Romania	Research Site	Bucharest
Romania	Research Site	Sibiu
Romania	Research Site	Timisoara
Russian Federation	Research Site	Barnaul	RUSSIAsia
Russian Federation	Research Site	Izhevsk	RUSSIAsia
Russian Federation	Research Site	Kursk	RUSSIAsia
Russian Federation	Research Site	Sochi	RUSSIAsia
Russian Federation	Research Site	Voronezh	RUSSIAsia
Serbia	Research Site	Belgrade	SERBIAbia
Serbia	Research Site	Beograd	SERBIAbia
Serbia	Research Site	Nis	SERBIAbia
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Overport	Durban
South Africa	Research Site	Panorama	Cape Town
South Africa	Research Site	PORt Elizabeth
South Africa	Research Site	TyGERberg	Cape Town
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
Switzerland	Research Site	Aarau
Switzerland	Research Site	Locarno
Switzerland	Research Site	Sursee
Taiwan	Research Site	Kaohsiung	TAIWANwan
Taiwan	Research Site	TAIWANpei	TAIWANwan
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Reading	Berkshire
United Kingdom	Research Site	Westgate Road	Newcastle Upon Tyne
United States	Research Site	Canton	Ohio
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Durham	North Carolina
United States	Research Site	Fort Myers	Florida
United States	Research Site	Gainsville	Florida
United States	Research Site	Greenbrae	California
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norwich	Connecticut
United States	Research Site	Ocala	Florida
United States	Research Site	Omaha	Nebraska
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	PORTUGALt St. Lucie	Florida
United States	Research Site	Richmond	Virginia
United States	Research Site	Rockville	Maryland
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Seattle	Washington
United States	Research Site	Washington	District of Columbia
United States	Research Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Czech Republic,  Finland,  France,  Germany,  Hungary,  India,  Italy,  Korea, Republic of,  Netherlands,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Median time (in months) from randomisation until death using the Kaplan-Meier method.	Patients were followed for survival up to 40 months	No
Secondary	Progression Free Survival	Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline	Patients were followed for progression up to 40 months	No
Secondary	Incidence of Skeletal Related Events	Median time (in months) from randomisation until occurrence of a skeletal related event using the Kaplan-Meier method, where skeletal related event is defined as the first occurrence of a pathological fracture, a vertebral compression fracture not related to trauma, prophylactic surgery or radiation for impending fracture or spinal cord compression, or a spinal cord compression.	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)	No
Secondary	Time to Prostate-specific Antigen (PSA) Progression	Median time (in months) from randomisation until first PSA value >50% higher than baseline of at least 5ng/ml seen in at least 2 consecutive PSA values at least 2 weeks apart using the Kaplan-Meier method.	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)	No
Secondary	Time to Pain Progression	Median time (in months) from randomisation until date of first assessment of increased pain using the Kaplan-Meier method, where increased pain event is defined as the first of a patient requiring opiate medication for duration of =1 week for pain due to prostate cancer metastasis, pain due to metastasis that has an increase in the worst pain item of the Brief Pain Inventory (BPI) from baseline to a minimum score of 5 with no decrease in analgesic use, or pain due to metastasis requiring radionuclide therapy, radiation therapy or surgery.	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)	No
Secondary	Pain Response	Number of patients with a pain response, defined as a decrease in brief pain inventory questionnaire (BPI) of at least 2 points from baseline or a decrease in opiate use of 25% from baseline.	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)	No
Secondary	Health Related Quality of Life	Median time (in months) from randomisation until deterioration of Health Related Quality of Life using the Kaplan-Meier method, where deterioration is defined as a change from baseline of less than or equal to -6 points in Total FACT-P score maintained for 2 consecutive visits.	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)	No
Secondary	PSA Response	PSA response defined as >50% decrease in serum PSA values from baseline seen in at least 2 consecutive PSA values at least 2 weeks apart.	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)	No

External Links

•   Cancer Study Locator (US and Canada only)