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

Phase 3

Completed

Conditions: Prostate Cancer

Interventions: Drug: ZD4054
Drug: Placebo

Registration Number: NCT00554229

Lead Sponsor: AstraZeneca

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 896

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 metastases)
Increasing Prostate Specific Antigen (PSA) over a one month period
No pain, or mild pain from prostate cancer
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.

Currently using opiates based pain killers)
Previous treatment with chemotherapy (paclitaxel, docetaxel, and mitoxantrone)
Suffering from heart failure or had a myocardial infarction within last 6 months
A history of epilepsy or seizures

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ZD4054	ZD4054	ZD4054 10 mg oral tablet once daily
Placebo	Placebo	Matching Placebo, oral tablets once daily

Primary Outcome Measures

Name	Time	Method
Overall Survival	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

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	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	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	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	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	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	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	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	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	PK samples were performed at randomisation, Week 4, Week 8 and Week 12