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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00554229
Recruitment Status : Completed
First Posted : November 6, 2007
Results First Posted : May 31, 2012
Last Update Posted : February 8, 2016
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE November 2, 2007
First Posted Date  ICMJE November 6, 2007
Results First Submitted Date  ICMJE April 26, 2012
Results First Posted Date  ICMJE May 31, 2012
Last Update Posted Date February 8, 2016
Study Start Date  ICMJE November 2007
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2012)
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2007)
Overall survival [ Time Frame: study visits and assessments every 4 weeks for first 12 weeks then every 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2012)
  • 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
  • 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
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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
  • Pharmacokinetic Characteristics of ZD4054 [ Time Frame: PK samples were performed at randomisation, Week 4, Week 8 and Week 12 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2007)
  • Progression free survival [ Time Frame: study visits and assessments every 4 weeks for first 12 weeks then every 12 weeks ]
  • Tolerability and safety profile of ZD4054 [ Time Frame: Assessed at each visit ]
  • Time to use of opiates
  • Incidence of skeletal related events [ Time Frame: Assessed at each visit ]
  • Bone metastases formation
  • Health Related Quality of Life [ Time Frame: Assessed every visit ]
  • Time to prostate-specific antigen (PSA) progression
  • Time to pain progression
  • Time to initiation of chemotherapy
  • Pharmacokinetic characteristics of ZD4054 [ Time Frame: Assessed at each visit ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Hormone Resistant Prostate Cancer With Bone Metastases
Official Title  ICMJE 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.
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: ZD4054
    ZD4054 10 mg oral tablet once daily
    Other Name: Zibotentan
  • Drug: Placebo
    Matching placebo oral tablet once daily
Study Arms  ICMJE
  • Experimental: ZD4054
    ZD4054 10 mg oral tablet once daily
    Intervention: Drug: ZD4054
  • Placebo Comparator: Placebo
    Matching Placebo, oral tablets once daily
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 29, 2012)
896
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2007)
580
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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,   United States
Removed Location Countries Former Serbia and Montenegro
 
Administrative Information
NCT Number  ICMJE NCT00554229
Other Study ID Numbers  ICMJE D4320C00014
2007-003227-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party AstraZeneca
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Martin Gleave, MD, FRCSC, FACS The Prostate Centre at Vancouver General Hospital
Principal Investigator: Joel B Nelson, MD University of Pittsburgh
PRS Account AstraZeneca
Verification Date April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP