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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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 - Median time (in months) from randomisation until death using the Kaplan-Meier method.
Timepoint [1] 0 0
Patients were followed for survival up to 40 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Patients were followed for progression up to 40 months
Secondary outcome [2] 0 0
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.
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 - 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.
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 - 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.
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 - 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.
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 - 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.
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 - 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.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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Research Site - Redcliffe
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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
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- Wodonga
Recruitment postcode(s) [8] 0 0
- Perth
Recruitment postcode(s) [9] 0 0
- Subiaco
Recruitment outside Australia
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California
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Wisconsin
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Argentina
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Buenos Aires
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Santa Fe
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Helsinki
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Durban
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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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Stockholm
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Berkshire
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Newcastle Upon Tyne
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London
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United Kingdom
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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/show/NCT00617669
Trial related presentations / publications
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
Other publications