A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer (ENTHUSE M1C)

September 4, 2012 updated by: AstraZeneca

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1494

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Placebo + Docetaxel
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
Drug: Docetaxel
intravenous infusion given every three weeks
Other Names:
  • Taxotere®
Drug: Placebo
placebo oral tablet once daily
Experimental: ZD4054 + Docetaxel
ZD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
Drug: Docetaxel
intravenous infusion given every three weeks
Other Names:
  • Taxotere®
Drug: ZD4054
10 mg oral once daily dose
Other Names:
  • Zibotentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Patients were followed for survival up to 40 months
Median time (in months) from randomisation until death using the Kaplan-Meier method.
Patients were followed for survival up to 40 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: Patients were followed for progression up to 40 months
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
Incidence of Skeletal Related Events
Time Frame: 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)
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)
Time to Prostate-specific Antigen (PSA) Progression
Time Frame: 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)
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)
Time to Pain Progression
Time Frame: 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)
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)
Pain Response
Time Frame: 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)
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)
Health Related Quality of Life
Time Frame: 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)
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)
PSA Response
Time Frame: 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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Karim Fizazi, MD, PhD, Gustave Roussy, Cancer Campus, Grand Paris
  • Principal Investigator: Judd W Moul, MD, FACS, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

January 24, 2008

First Submitted That Met QC Criteria

February 6, 2008

First Posted (Estimate)

February 18, 2008

Study Record Updates

Last Update Posted (Estimate)

September 10, 2012

Last Update Submitted That Met QC Criteria

September 4, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4320C00033

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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