A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Hormone Resistant Prostate Cancer With Bone Metastases

Prostate Cancer Clinical Trial

— ENTHUSE M1  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00554229
• Other study ID #: D4320C00014
• Secondary ID: 2007-003227-20
• Status: Completed
• Phase: Phase 3
• First received: November 2, 2007
• Last updated: January 15, 2016
• Start date: November 2007
• Est. completion date: August 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 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.

Other known NCT identifiers

• NCT00707395

Recruitment information / eligibility

• Status: Completed
• Enrollment: 896
• Est. completion date: August 2011
• Est. primary completion date: July 2010
• 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.

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

Study Design

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ZD4054
ZD4054 10 mg oral tablet once daily
• Placebo
Matching placebo oral tablet once daily

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires	Buenos Aires Province
Argentina	Research Site	Santa Fe	Santa Fe Province
Australia	Research Site	Ashford	South Australia
Australia	Research Site	Hornsby	New South Wales
Australia	Research Site	Redcliffe	Queensland
Australia	Research Site	St Leonards	New South Wales
Australia	Research Site	Subiaco	Western Australia
Austria	Research Site	Graz
Austria	Research Site	Wels
Belgium	Research Site	Brussels
Belgium	Research Site	Gent
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Brazil	Research Site	Belo Horizonte	Minas Gerais
Brazil	Research Site	Curitiba	Parana
Brazil	Research Site	Fortaleza	Ceara
Brazil	Research Site	Goiania	Goias
Brazil	Research Site	Porto Alegre	Rio Grande do Sul
Brazil	Research Site	Ribeirao Preto	Sao Paulo
Brazil	Research Site	Santo Andre	Sao Paulo
Brazil	Research Site	Sao Paulo
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Granby	Quebec
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Kentville	Nova Scotia
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	Laval	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	North York	Ontario
Canada	Research Site	Oakville	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Point-Claire	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Haidian District	Beijing
China	Research Site	Nanjing	Jiangsu
China	Research Site	Pudong New Area	Shanghai
China	Research Site	Shanghai	Shanghai
China	Research Site	Wuhan	Hubei
China	Research Site	Xi Cheng District	Beijing
China	Research Site	Xi'an	Shanxi
China	Research Site	Xicheng District	Beijing
China	Research Site	Xuhui District	Shanghai
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Prague 4	Prague
Czech Republic	Research Site	Prague 6	Prague
Czech Republic	Research Site	Usti nad Labem
Denmark	Research Site	Aalborg
Denmark	Research Site	Aarhus
Denmark	Research Site	Herlev
Denmark	Research Site	Kobenhavn
Finland	Research Site	Joensuu
Finland	Research Site	Kajaanintie
Finland	Research Site	Tampere
France	Research Site	Montpellier
France	Research Site	Paris
France	Research Site	Poitiers Cedex
France	Research Site	Suresnes
France	Research Site	Toulouse
France	Research Site	Villejuif
Germany	Research Site	Augsburg
Germany	Research Site	Bad Gegeberg
Germany	Research Site	Berlin
Germany	Research Site	Emmendingen
Germany	Research Site	Kirchheim	Teck
Germany	Research Site	Leipzig
Germany	Research Site	Luebeck
Germany	Research Site	Mannheim
Germany	Research Site	Muenchen
Germany	Research Site	Planegg	Muenchen
Germany	Research Site	Reutlingen
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Shatin
Hong Kong	Research Site	Tuen Mun
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	Szeged
India	Research Site	Bhopal	Madhya Pradesh
India	Research Site	Bikaner	Rajasthan
India	Research Site	Chandigarh	Punjab
India	Research Site	Gujarat
India	Research Site	Jaipur	Rajasthan
India	Research Site	Kolkota	West Bengal
India	Research Site	Ludhiana	Punjab
India	Research Site	Mumbai	Maharashtra
India	Research Site	New Delhi
India	Research Site	Rohini	Delhi
India	Research Site	Trivandrum	Kerala
Italy	Research Site	Milan
Italy	Research Site	Rome
Japan	Research Site	Asahi-City	Chiba
Japan	Research Site	Bunkyo-ku	Tokyo
Japan	Research Site	Chiba-City	Chiba
Japan	Research Site	Fuchu_city	Tokyo
Japan	Research Site	Fukuoka-City	Fukuoka
Japan	Research Site	Hamamatsu-city	Shizuoka
Japan	Research Site	Itabashi-Ku	Tokyo
Japan	Research Site	Kita-gun	Kagawa
Japan	Research Site	Kobe-City	Hyogo
Japan	Research Site	Kyoto-City	Kyoto
Japan	Research Site	Maebashi-City	Gunma
Japan	Research Site	Matsuyama-City	Ehime
Japan	Research Site	Meguro-ku	Tokyo
Japan	Research Site	Mitaka-City	Tokyo
Japan	Research Site	Nagasaki
Japan	Research Site	Narashino-city	Chiba
Japan	Research Site	Oita-City	Oita
Japan	Research Site	Osaka-City	Osaka
Japan	Research Site	Osaka-Sayama-City	Osaka
Japan	Research Site	Otake-City	Hiroshima
Japan	Research Site	Sagamihara-City	Kanagawa
Japan	Research Site	Sapporo-City	Hokkaido
Japan	Research Site	Sendai-City	Miyagi
Japan	Research Site	Shinjuku-ku	Tokyo
Japan	Research Site	Suita-City	Osaka
Japan	Research Site	Sunto-gun	Shizuoka
Japan	Research Site	Tsukuba-City	Ibaraki
Japan	Research Site	Wako-City	Saitama
Korea, Republic of	Research Site	Gangnam-gu	Seoul
Korea, Republic of	Research Site	Heungduk-gu Cheongju	Chungbuk
Korea, Republic of	Research Site	Seo-gu	Pusan
Korea, Republic of	Research Site	Seongnam-si	Gyeonggi-do
Korea, Republic of	Research Site	Songpa-gu	Seoul
Mexico	Research Site	Distrito Federal Ciudad
Mexico	Research Site	Metepec	Estado de Mexico
Mexico	Research Site	Mexico City
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Eindhoven
Netherlands	Research Site	Groningen
Netherlands	Research Site	Nijmegen
Poland	Research Site	Bialystok
Poland	Research Site	Koscierzyna
Poland	Research Site	Krakow
Poland	Research Site	Rzeszow
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Portugal	Research Site	Coimbra
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kursk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Sochi
Russian Federation	Research Site	St. Petersgurg
Russian Federation	Research Site	Stary Oskol	Belgorodskaya region
Russian Federation	Research Site	Voronezh
Serbia	Research Site	Belgrade
Serbia	Research Site	Nis
Serbia	Research Site	Novi Sad
Singapore	Research Site	Singapore
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Pietermaritzburg
South Africa	Research Site	Port Elizabeth
South Africa	Research Site	Tygerberg	Cape Town
Sweden	Research Site	Goteborg
Sweden	Research Site	Gothenburg
Sweden	Research Site	Stockholm
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Locarno
Switzerland	Research Site	Sursee
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
United Kingdom	Research Site	Cambridge	Cambridgeshire
United Kingdom	Research Site	Huddersfield	Yorkshire
United Kingdom	Research Site	London
United Kingdom	Research Site	Maidstone	Kent
United Kingdom	Research Site	Reading	Berkshire
United States	Research Site	Burlington	Vermont
United States	Research Site	Canton	Ohio
United States	Research Site	Des Moines	Iowa
United States	Research Site	Gainsville	Florida
United States	Research Site	Greenbrae	California
United States	Research Site	Los Angeles	California
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norfolk	Virginia
United States	Research Site	Norwich	Connecticut
United States	Research Site	Palm Springs	California
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port St.Lucie	Florida
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Mateo	California
United States	Research Site	Seattle	Washington
United States	Research Site	Tucson	Arizona
United States	Research Site	Washington	District of Columbia
United States	Research Site	Wheeling	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Russian Federation,  Serbia,  Singapore,  South Africa,  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	From date of randomization until date of death, assessed up to 32 months	No
Secondary	Progression Free Survival	Median time (in months) from randomisation until clinical progression of disease, where 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, using the Kaplan-Meier method	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	No
Secondary	Time to Use of Opiates	Median time (in months) from randomisation until use of opiates for disease-related symptoms for a duration =1 week using the Kaplan-Meier method	From date of randomization until use of opiates for disease-related symptoms for a duration =1 week, assessed up to 31 months	No
Secondary	Incidence of Skeletal Related Events	Median time (in months) from randomisation until occurrence of a skeletal related event, 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, using the Kaplan-Meier method.	From date of randomization until occurrence of a skeletal related event, assessed up to 31 months	No
Secondary	Bone Metastases Formation	Median time (in months) from randomisation to appearance of =4 new bone lesions using the Kaplan-Meier method	Patients were assessed every 12 weeks	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.	Patients were assessed at every visit	No
Secondary	Time to Prostate-specific Antigen (PSA) Progression	Median time (in months) from randomisation to 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.	Patients were assessed every 12 weeks	No
Secondary	Time to Pain Progression	Median time (in months) from randomisation to first assessment of an increased pain event, 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.	Patients were assessed every 12 weeks	No
Secondary	Time to Initiation of Chemotherapy	Median time (in months) from randomisation to first administration of any chemotherapy using the Kaplan-Meier method	Patients were assessed every 12 weeks	No
Secondary	Pharmacokinetic Characteristics of ZD4054		PK samples were performed at randomisation, Week 4, Week 8 and Week 12	No

External Links

•   Cancer Study Locator (US and Canada only)