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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00554229
First received: November 2, 2007
Last updated: August 29, 2012
Last verified: April 2012
  Purpose

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.

Condition Intervention Phase
Prostate Cancer
Drug: ZD4054
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From date of randomization until date of death, assessed up to 32 months ] [ Designated as safety issue: No ]
    Median time (in months) from randomisation until death using the Kaplan-Meier method


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 896
Study Start Date: November 2007
Study Completion Date: August 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ZD4054
ZD4054 10 mg oral tablet once daily
Drug: ZD4054
ZD4054 10 mg oral tablet once daily
Other Name: Zibotentan
Placebo Comparator: Placebo
Matching Placebo, oral tablets once daily
Drug: Placebo
Matching placebo oral tablet once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00554229

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Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00554229     History of Changes
Obsolete Identifiers: NCT00707395
Other Study ID Numbers: D4320C00014, 2007-003227-20
Study First Received: November 2, 2007
Results First Received: April 26, 2012
Last Updated: August 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Hormone Resistant Prostate Cancer
Endothelin A Receptor Antagonist
Endothelin A
Endothelin A antagonist

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014