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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00617669




Registration number
NCT00617669
Ethics application status
Date submitted
24/01/2008
Date registered
18/02/2008
Date last updated
10/09/2012

Titles & IDs
Public title
A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer
Scientific 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
Secondary ID [1] 0 0
D4320C00033
Universal Trial Number (UTN)
Trial acronym
ENTHUSE M1C
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Docetaxel
Treatment: Drugs - ZD4054
Treatment: Drugs - Placebo

Active comparator: Placebo + Docetaxel - placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks

Experimental: ZD4054 + Docetaxel - ZD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks


Treatment: Drugs: Docetaxel
intravenous infusion given every three weeks

Treatment: Drugs: ZD4054
10 mg oral once daily dose

Treatment: Drugs: Placebo
placebo oral tablet once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Patients were followed for survival up to 40 months
Secondary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
Patients were followed for progression up to 40 months
Secondary outcome [2] 0 0
Incidence of Skeletal Related Events
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Time to Prostate-specific Antigen (PSA) Progression
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Time to Pain Progression
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Pain Response
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Health Related Quality of Life
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
PSA Response
Timepoint [7] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2011
Sample size
Target
Accrual to date
Final
1494
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Darlinghurst
Recruitment hospital [2] 0 0
Research Site - St Leonards
Recruitment hospital [3] 0 0
Research Site - Wollongong
Recruitment hospital [4] 0 0
Research Site - Redcliffe
Recruitment hospital [5] 0 0
Research Site - Ashford
Recruitment hospital [6] 0 0
Research Site - Footscray
Recruitment hospital [7] 0 0
Research Site - Wodonga
Recruitment hospital [8] 0 0
Research Site - Perth
Recruitment hospital [9] 0 0
Research Site - Subiaco
Recruitment postcode(s) [1] 0 0
- Darlinghurst
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- St Leonards
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- Wollongong
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- Redcliffe
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- Ashford
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- Footscray
Recruitment postcode(s) [7] 0 0
- Wodonga
Recruitment postcode(s) [8] 0 0
- Perth
Recruitment postcode(s) [9] 0 0
- Subiaco
Recruitment outside Australia
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United States of America
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California
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Connecticut
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Nebraska
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North Carolina
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CZECHOSLOVAKIA Republic
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Jablonec nad Nisou
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Olomouc
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Helsinki
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Muenster
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Wuppertal
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Serbia
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Cape Town
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Durban
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Bloemfontein
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PORt Elizabeth
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Spain
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Madrid
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Valencia
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Sweden
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Stockholm
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Uppsala
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Locarno
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Sursee
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Taiwan
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United Kingdom
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Berkshire
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Newcastle Upon Tyne
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London
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00617669
Trial related presentations / publications
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. Erratum In: J Clin Oncol. 2014 Oct 20;32(30):3461. Fizazi, Karim S [Corrected to Fizazi, Karim].
Public notes

Contacts
Principal investigator
Name 0 0
Karim Fizazi, MD, PhD
Address 0 0
Gustave Roussy, Cancer Campus, Grand Paris
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00617669