A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Hormone Resistant Prostate Cancer With Bone Metastases (ENTHUSE M1)

January 15, 2016 updated by: AstraZeneca

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

896

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

  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 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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ZD4054
ZD4054 10 mg oral tablet once daily
Drug: ZD4054
ZD4054 10 mg oral tablet once daily
Other Names:
  • Zibotentan
PLACEBO_COMPARATOR: Placebo
Matching Placebo, oral tablets once daily
Drug: Placebo
Matching placebo oral tablet once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From date of randomization until date of death, assessed up to 32 months
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 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
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
Time to Use of Opiates
Time Frame: From date of randomization until use of opiates for disease-related symptoms for a duration ≥1 week, assessed up to 31 months
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
Incidence of Skeletal Related Events
Time Frame: From date of randomization until occurrence of a skeletal related event, assessed up to 31 months
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
Bone Metastases Formation
Time Frame: Patients were assessed every 12 weeks
Median time (in months) from randomisation to appearance of ≥4 new bone lesions using the Kaplan-Meier method
Patients were assessed every 12 weeks
Health Related Quality of Life
Time Frame: Patients were assessed at every visit
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
Time to Prostate-specific Antigen (PSA) Progression
Time Frame: Patients were assessed every 12 weeks
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
Time to Pain Progression
Time Frame: Patients were assessed every 12 weeks
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
Time to Initiation of Chemotherapy
Time Frame: Patients were assessed every 12 weeks
Median time (in months) from randomisation to first administration of any chemotherapy using the Kaplan-Meier method
Patients were assessed every 12 weeks
Pharmacokinetic Characteristics of ZD4054
Time Frame: PK samples were performed at randomisation, Week 4, Week 8 and Week 12
PK samples were performed at randomisation, Week 4, Week 8 and Week 12

Collaborators and Investigators

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

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Martin Gleave, MD, FRCSC, FACS, The Prostate Centre at Vancouver General Hospital
  • Principal Investigator: Joel B Nelson, MD, University of Pittsburgh

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

November 1, 2007

Primary Completion (ACTUAL)

July 1, 2010

Study Completion (ACTUAL)

August 1, 2011

Study Registration Dates

First Submitted

November 2, 2007

First Submitted That Met QC Criteria

November 2, 2007

First Posted (ESTIMATE)

November 6, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

February 8, 2016

Last Update Submitted That Met QC Criteria

January 15, 2016

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4320C00014
  • 2007-003227-20 (EUDRACT_NUMBER)

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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