Prostate Cancer
Conditions
Keywords
rising PSA, bone metastases, Clinical study, pain-free or mildly symptomatic
Brief summary
This study is being carried out to see if ZD4054 (Zibotentan) is effective in treating prostate cancer and spread of cancer to the bone, and if so, how it compares with placebo (sugar pill). The study will also provide further information on the safety of ZD4054 (Zibotentan).
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Surgically or medically castrated * Bone metastasis * Rising PSA
Exclusion criteria
* Opiate use * Prior chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | Follow-up for progression/death was 4-weekly for 2 years after first dose and 3-monthly thereafter. 'Final analysis' results are given - the most recent formal analysis (data cut-off 18th December 2008). | Median time (in days) from randomisation until disease progression, 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 or death using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Death | Follow-up for progression/death was 4-weekly for 2 years after first dose and 3-monthly thereafter. After progression survival was assessed 6-monthly. 'Final analysis' results are given - the most recent formal analysis (data cut-off 18th December 2008). | Median time (in days) from randomisation until death using the Kaplan-Meier method. |
| Change in Total Prostate Specific Antigen (PSA) Over Time | Baseline to 12 weeks. 'Initial analysis' results are given - the most recent formal analysis (data cut-off 10th April 2006). | Percentage change in total Prostate Specific Antigen (PSA) (ng/mL) from baseline to 12 weeks. |
| Objective Response Rate (ORR) | For patients with measurable disease at baseline, Response Evaluation Criteria in Solid Tumours (RECIST) scans were 12-weekly from randomisation. 'Initial analysis' results are given - the most recent formal analysis (data cut-off 10th April 2006). | Using the Response Evaluation Criteria in Solid Tumours (RECIST), an objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR), which is subsequently confirmed as per RECIST. Objective Response Rate (ORR) is defined as the percentage of patients with OR. |
| Change in Number of Bone Metastases Over Time | Baseline to last available post-baseline scan prior to discontinuation, up to maximum of 1164 days. | Percentage change in the number of bone metastases from baseline to last available post-baseline scan prior to discontinuation. |
Countries
Australia, Belgium, Canada, Denmark, Finland, France, Indonesia, Netherlands, Norway, Poland, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
447 patients with prostate cancer who had bone metastases with no pain or mild symptoms of pain and a rising serum Prostate Specific Antigen (PSA), despite a serum testosterone of \<= 2.4 nmol/L (70 ng/dL), were recruited between 14th July 2004 and 10th January 2006.
Pre-assignment details
135 of the 447 enrolled patients were not randomised to treatments groups: 126 failed screening and 9 did not meet one or more of the study inclusion or exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo oral tablet once daily, with best supportive care | 107 |
| ZD4054 10 mg ZD4054 10 mg oral tablet once daily, with best supportive care | 107 |
| ZD4054 15 mg ZD4054 15 mg oral tablet once daily, with best supportive care | 98 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Consent expired | 7 | 10 | 9 |
| Overall Study | Continuing on study off treatment | 14 | 13 | 16 |
| Overall Study | Eligibility criteria not fulfilled | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Reasons not specified | 2 | 1 | 1 |
| Overall Study | Study-specific discontinuation criteria | 75 | 74 | 62 |
| Overall Study | Withdrawal by Subject | 7 | 7 | 6 |
Baseline characteristics
| Characteristic | Placebo | ZD4054 10 mg | ZD4054 15 mg | Total |
|---|---|---|---|---|
| Age Continuous | 71 years STANDARD_DEVIATION 9 | 70 years STANDARD_DEVIATION 8 | 69 years STANDARD_DEVIATION 8 | 70 years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized African-American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 106 Participants | 107 Participants | 93 Participants | 306 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not a specific ethnic group | 99 Participants | 95 Participants | 87 Participants | 281 Participants |
| Race/Ethnicity, Customized Oriental | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 107 Participants | 107 Participants | 98 Participants | 312 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 93 / 107 | 86 / 107 | 87 / 98 |
| serious Total, serious adverse events | 26 / 107 | 18 / 107 | 16 / 98 |
Outcome results
Primary
Time to Progression (TTP)
Median time (in days) from randomisation until disease progression, 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 or death using the Kaplan-Meier method.
Time frame: Follow-up for progression/death was 4-weekly for 2 years after first dose and 3-monthly thereafter. 'Final analysis' results are given - the most recent formal analysis (data cut-off 18th December 2008).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Progression (TTP) | 111 Days |
| ZD4054 10 mg | Time to Progression (TTP) | 138 Days |
| ZD4054 15 mg | Time to Progression (TTP) | 113 Days |
Secondary
Change in Number of Bone Metastases Over Time
Percentage change in the number of bone metastases from baseline to last available post-baseline scan prior to discontinuation.
Time frame: Baseline to last available post-baseline scan prior to discontinuation, up to maximum of 1164 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Number of Bone Metastases Over Time | 187.1 Percentage Change | Standard Deviation 212.6 |
| ZD4054 10 mg | Change in Number of Bone Metastases Over Time | 113.4 Percentage Change | Standard Deviation 195.6 |
| ZD4054 15 mg | Change in Number of Bone Metastases Over Time | 189 Percentage Change | Standard Deviation 245.2 |
Secondary
Change in Total Prostate Specific Antigen (PSA) Over Time
Percentage change in total Prostate Specific Antigen (PSA) (ng/mL) from baseline to 12 weeks.
Time frame: Baseline to 12 weeks. 'Initial analysis' results are given - the most recent formal analysis (data cut-off 10th April 2006).
Population: The analysis population only includes patients with baseline and Week 12 PSA measurements
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Total Prostate Specific Antigen (PSA) Over Time | 110.4 Percentage Change in PSA | Standard Deviation 179.16 |
| ZD4054 10 mg | Change in Total Prostate Specific Antigen (PSA) Over Time | 131.6 Percentage Change in PSA | Standard Deviation 454.35 |
| ZD4054 15 mg | Change in Total Prostate Specific Antigen (PSA) Over Time | 69.34 Percentage Change in PSA | Standard Deviation 99.14 |
Secondary
Objective Response Rate (ORR)
Using the Response Evaluation Criteria in Solid Tumours (RECIST), an objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR), which is subsequently confirmed as per RECIST. Objective Response Rate (ORR) is defined as the percentage of patients with OR.
Time frame: For patients with measurable disease at baseline, Response Evaluation Criteria in Solid Tumours (RECIST) scans were 12-weekly from randomisation. 'Initial analysis' results are given - the most recent formal analysis (data cut-off 10th April 2006).
Population: Only patients with measurable disease at the baseline were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Objective Response Rate (ORR) | 0 percentage of participants |
| ZD4054 10 mg | Objective Response Rate (ORR) | 0 percentage of participants |
| ZD4054 15 mg | Objective Response Rate (ORR) | 0 percentage of participants |
Secondary
Time to Death
Median time (in days) from randomisation until death using the Kaplan-Meier method.
Time frame: Follow-up for progression/death was 4-weekly for 2 years after first dose and 3-monthly thereafter. After progression survival was assessed 6-monthly. 'Final analysis' results are given - the most recent formal analysis (data cut-off 18th December 2008).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Death | 596 Days |
| ZD4054 10 mg | Time to Death | 706 Days |
| ZD4054 15 mg | Time to Death | 717 Days |