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

Primary Purpose

Prostate Cancer

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Docetaxel

ZD4054

Placebo

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Hormone Resistant Prostate Cancer, Endothelin A Receptor Antagonist, Endothelin A, Endothelin A antagonist

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Placebo + Docetaxel

ZD4054 + Docetaxel

Arm Description

placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks

ZD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks

Outcomes

Primary Outcome Measures

Overall Survival

Median time (in months) from randomisation until death using the Kaplan-Meier method.

Secondary Outcome Measures

Progression Free Survival

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

Incidence of Skeletal Related Events

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.

Time to Prostate-specific Antigen (PSA) Progression

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.

Time to Pain Progression

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.

Pain Response

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.

Health Related Quality of Life

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.

PSA Response

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.

Full Information

NCT ID

NCT00617669

First Posted

January 24, 2008

Last Updated

September 4, 2012

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT00617669

Brief Title

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

Acronym

ENTHUSE M1C

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 Type

Interventional

2. Study Status

Record Verification Date

April 2012

Overall Recruitment Status

Completed

Study Start Date

January 2008 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

Hormone Resistant Prostate Cancer, Endothelin A Receptor Antagonist, Endothelin A, Endothelin A antagonist

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

1494 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo + Docetaxel

Arm Type

Active Comparator

Arm Description

placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks

Arm Title

ZD4054 + Docetaxel

Arm Type

Experimental

Arm Description

ZD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Taxotere®

Intervention Description

intravenous infusion given every three weeks

Intervention Type

Drug

Intervention Name(s)

ZD4054

Other Intervention Name(s)

Zibotentan

Intervention Description

10 mg oral once daily dose

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo oral tablet once daily

Primary Outcome Measure Information:

Title

Overall Survival

Description

Median time (in months) from randomisation until death using the Kaplan-Meier method.

Time Frame

Patients were followed for survival up to 40 months

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

Time Frame

Patients were followed for progression up to 40 months

Title

Incidence of Skeletal Related Events

Description

Time Frame