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

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ClinicalTrials.gov Identifier: NCT00617669
Recruitment Status : Completed
First Posted : February 18, 2008
Results First Posted : May 31, 2012
Last Update Posted : September 10, 2012
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.


Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Docetaxel Drug: ZD4054 Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1494 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official 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
Study Start Date : January 2008
Actual Primary Completion Date : May 2011
Actual Study Completion Date : July 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

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 Name: 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 Name: Taxotere®

Drug: ZD4054
10 mg oral once daily dose
Other Name: Zibotentan




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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.

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00617669


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Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Karim Fizazi, MD, PhD Gustave Roussy, Cancer Campus, Grand Paris
Principal Investigator: Judd W Moul, MD, FACS Duke University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00617669     History of Changes
Other Study ID Numbers: D4320C00033
First Posted: February 18, 2008    Key Record Dates
Results First Posted: May 31, 2012
Last Update Posted: September 10, 2012
Last Verified: April 2012

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

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Hormones
Endothelin A Receptor Antagonists
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Endothelin Receptor Antagonists