Prostate Cancer
Conditions
Keywords
Hormone Resistant Prostate Cancer, Endothelin A Receptor Antagonist, Endothelin A, Endothelin A antagonist
Brief summary
Enthuse M0 is a large phase III clinical trial studying the efficacy of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC). This clinical trial will test if the Endothelin A Receptor Antagonist ZD4054 (Zibotentan) can improve progression-free survival and overall survival against a background of existing prostate cancer treatments. ZD4054 (Zibotentan) is a new type of agent, which is thought to slow tumour growth and spread by blocking Endothelin receptor activity. This trial will look at the effects of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC) patients who have had rising PSA after surgical or medical castration but have no evidence of metastases. All patients participating in this clinical trial will receive existing 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.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients who answer TRUE to the following criteria may be eligible to participate in this study. * Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has NOT spread to the other parts of the body (metastases). Patients with lymph node involvement may be eligible if specified criteria is met. * 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 may NOT be eligible to participate in this study. * Currently using opiate based pain killers for cancer related pain * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of randomization until date of death, assessed up to 33 months | Number of participants who have died at early analysis data cut off (DCO) |
| Progression Free Survival | Participants were followed up for progression every 4 weeks for the first 16 weeks then every 16 weeks | Number of participants who have a progression event at the early analysis DCO, 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 |
Secondary
| Measure | Time frame |
|---|---|
| Health Related Quality of Life | Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks |
| Time to Prostate-specific Antigen (PSA) Progression | Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks |
| Time to Symptomatic Progression | Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Hungary, India, Ireland, Israel, Italy, Japan, Latvia, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Romania, Russia, Serbia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
2577 patients with hormone-resistant prostate cancer patients and bone metastasis were recruited between 15th January 2008 and 3rd May 2011
Pre-assignment details
1156 of the 2577 enrolled patients were not randomised to treatment groups as they failed screening
Participants by arm
| Arm | Count |
|---|---|
| ZD4054 ZD4054 10 mg oral tablet once daily | 705 |
| Placebo Placebo oral tablet once daily | 716 |
| Total | 1,421 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 164 | 44 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Other termination reason | 493 | 613 |
| Overall Study | Protocol Violation | 4 | 11 |
| Overall Study | Withdrawal by Subject | 42 | 46 |
Baseline characteristics
| Characteristic | ZD4054 | Placebo | Total |
|---|---|---|---|
| Age Continuous Overall | 72.4 years STANDARD_DEVIATION 7.8 | 72.5 years STANDARD_DEVIATION 7.8 | 72.45 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 705 Participants | 716 Participants | 1421 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 531 / 703 | 392 / 712 |
| serious Total, serious adverse events | 148 / 703 | 138 / 712 |
Outcome results
Primary
Overall Survival
Number of participants who have died at early analysis data cut off (DCO)
Time frame: From date of randomization until date of death, assessed up to 33 months
Population: The analysis population only includes patients recruited by the time of the early analysis (1 October 2010)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 | Overall Survival | 40 Participants |
| Placebo | Overall Survival | 39 Participants |
Primary
Progression Free Survival
Number of participants who have a progression event at the early analysis DCO, 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
Time frame: Participants were followed up for progression every 4 weeks for the first 16 weeks then every 16 weeks
Population: The analysis population only includes patients recruited by the time of the early analysis (1 October 2010)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 | Progression Free Survival | 131 Participants |
| Placebo | Progression Free Survival | 162 Participants |
Secondary
Health Related Quality of Life
Time frame: Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks
Secondary
Time to Prostate-specific Antigen (PSA) Progression
Time frame: Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks
Secondary
Time to Symptomatic Progression
Time frame: Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks