Metastases, Neoplasm, Prostatic Neoplasms
Conditions
Keywords
prostate cancer, Metastatic prostate cancer, bone metastases
Brief summary
The primary purpose of this study is to determine the safest dose of ZD4054 (Zibotentan)in men with prostate cancer
Interventions
DRUGZD4054 10 mg
1 x 10 mg oral tablets once daily
DRUGZD4054 15 mg
1 x 10 mg + 2 x 2.5 mg oral tablets once daily
DRUGZD4054 22.5 mg
2 x 10 mg + 2 x 2.5 mg oral tablets once daily
Sponsors
AstraZeneca
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men 18 years & older * Confirmed diagnosis of prostate cancer with bone metastases
Exclusion criteria
* No more than 2 prior chemotherapy regimens * No radiation, chemotherapy or bisphosphonates in the past 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) | Baseline to Day 29. | DLT is defined as experiencing Common Toxicity Criteria (CTC) grade 3 or 4 headache with onset within 24 h of receiving ZD4054, CTC grade 2 rhinitis leading to the withdrawal of the subject, or other CTC grade 3 or 4 toxicity that was considered to be related to ZD4054 treatment. The numbers of patients with a DLT are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Prostate Specific Antigen (PSA) | Baseline to Day 15. | Percentage change in total Prostate Specific Antigen (PSA) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100 |
| Change in Serum Concentration of Bone Alkaline Phosphatase (ALP) | Baseline to Day 15. | Percentage change in serum concentration of Bone Alkaline Phosphatase (ALP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100 |
| Total Prostate Specific Antigen (PSA) Concentration | Baseline to Day 15. | Total Prostate Specific Antigen (PSA) concentration at Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). |
| Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx) | Baseline to Day 15. | Percentage change in serum concentration of C-Terminal Telopeptide of Type I Collagen (CTx) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100 |
| Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) | Baseline to Day 15. | Percentage change in urine concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) (nmol BCE/mmol Creatinine) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100 |
| Change in Serum Concentration of Procollagen Type I N Propeptide (PINP) | Baseline to Day 15. | Percentage change in serum concentration of Procollagen Type I N Propeptide (PINP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100 |
Countries
United States
Participant flow
Recruitment details
22 male patients with metastatic prostate cancer and rising Prostate Specific Antigen (PSA) levels were recruited from 11th June 2003 (last subject completed on 31st October 2005). This study was conducted in 2 centres in the United States.
Pre-assignment details
6 of the 22 screened patients were not entered into the study as they did not fulfill the study eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| ZD4054 10 mg ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily | 3 |
| ZD4054 15 mg ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily | 10 |
| ZD4054 22.5 mg ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily | 3 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1: Dose Escalation Period | Adverse Event | 0 | 1 | 2 |
| Period 1: Dose Escalation Period | Disease progression | 0 | 1 | 0 |
| Period 1: Dose Escalation Period | Erroneously reported discont. criteria | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | ZD4054 10 mg | ZD4054 15 mg | ZD4054 22.5 mg | Total |
|---|---|---|---|---|
| Age Continuous Overall | 72.3 Years STANDARD_DEVIATION 3.21 | 64.6 Years STANDARD_DEVIATION 9.72 | 66.3 Years STANDARD_DEVIATION 8.08 | 66.4 Years STANDARD_DEVIATION 8.72 |
| Height | 177.33 Centimeters (cm) STANDARD_DEVIATION 4.51 | 177.10 Centimeters (cm) STANDARD_DEVIATION 8.02 | 176.33 Centimeters (cm) STANDARD_DEVIATION 5.03 | 177 Centimeters (cm) STANDARD_DEVIATION 6.69 |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 3 Participants | 9 Participants | 3 Participants | 15 Participants |
| Race/Ethnicity, Customized Oriental | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 3 Participants | 16 Participants |
| Weight | 87.33 Kilograms (kg) STANDARD_DEVIATION 19.035 | 107.8 Kilograms (kg) STANDARD_DEVIATION 21.06 | 103.00 Kilograms (kg) STANDARD_DEVIATION 35.595 | 103.06 Kilograms (kg) STANDARD_DEVIATION 23.405 |
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 | 3 / 3 | 10 / 10 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 2 / 10 | 2 / 3 |
Outcome results
Primary
Dose Limiting Toxicities (DLTs)
DLT is defined as experiencing Common Toxicity Criteria (CTC) grade 3 or 4 headache with onset within 24 h of receiving ZD4054, CTC grade 2 rhinitis leading to the withdrawal of the subject, or other CTC grade 3 or 4 toxicity that was considered to be related to ZD4054 treatment. The numbers of patients with a DLT are reported.
Time frame: Baseline to Day 29.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054 10 mg | Dose Limiting Toxicities (DLTs) | 0 Participants |
| ZD4054 15 mg | Dose Limiting Toxicities (DLTs) | 0 Participants |
| ZD4054 22.5 mg | Dose Limiting Toxicities (DLTs) | 2 Participants |
Secondary
Change in Serum Concentration of Bone Alkaline Phosphatase (ALP)
Percentage change in serum concentration of Bone Alkaline Phosphatase (ALP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100
Time frame: Baseline to Day 15.
Population: The analysis population includes only patients dosed with ZD4054
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ZD4054 10 mg | Change in Serum Concentration of Bone Alkaline Phosphatase (ALP) | -6.161 Percentage Change | Standard Deviation 9.616 |
| ZD4054 15 mg | Change in Serum Concentration of Bone Alkaline Phosphatase (ALP) | -9.197 Percentage Change | Standard Deviation 12.22 |
| ZD4054 22.5 mg | Change in Serum Concentration of Bone Alkaline Phosphatase (ALP) | -9.182 Percentage Change | Standard Deviation 10.644 |
Secondary
Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx)
Percentage change in serum concentration of C-Terminal Telopeptide of Type I Collagen (CTx) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100
Time frame: Baseline to Day 15.
Population: The analysis population includes only patients dosed with ZD4054
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ZD4054 10 mg | Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx) | -13.832 Percentage Change | Standard Deviation 19.003 |
| ZD4054 15 mg | Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx) | 44.855 Percentage Change | Standard Deviation 94.876 |
| ZD4054 22.5 mg | Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx) | 20.386 Percentage Change | Standard Deviation 31.094 |
Secondary
Change in Serum Concentration of Procollagen Type I N Propeptide (PINP)
Percentage change in serum concentration of Procollagen Type I N Propeptide (PINP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100
Time frame: Baseline to Day 15.
Population: The analysis population includes only patients dosed with ZD4054
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ZD4054 10 mg | Change in Serum Concentration of Procollagen Type I N Propeptide (PINP) | 7.865 Percentage Change | Standard Deviation 14.625 |
| ZD4054 15 mg | Change in Serum Concentration of Procollagen Type I N Propeptide (PINP) | 20.681 Percentage Change | Standard Deviation 44.217 |
| ZD4054 22.5 mg | Change in Serum Concentration of Procollagen Type I N Propeptide (PINP) | 113.012 Percentage Change | Standard Deviation 51.302 |
Secondary
Change in Total Prostate Specific Antigen (PSA)
Percentage change in total Prostate Specific Antigen (PSA) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100
Time frame: Baseline to Day 15.
Population: The analysis population includes only patients dosed with ZD4054
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ZD4054 10 mg | Change in Total Prostate Specific Antigen (PSA) | 2.235 Percentage Change | Standard Deviation 15.445 |
| ZD4054 15 mg | Change in Total Prostate Specific Antigen (PSA) | 10.986 Percentage Change | Standard Deviation 21.345 |
| ZD4054 22.5 mg | Change in Total Prostate Specific Antigen (PSA) | 18.404 Percentage Change | Standard Deviation 30.132 |
Secondary
Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx)
Percentage change in urine concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) (nmol BCE/mmol Creatinine) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = \[(measure at Day 15 - measure at baseline)/measure at baseline\]\*100
Time frame: Baseline to Day 15.
Population: The analysis population includes only patients dosed with ZD4054
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ZD4054 10 mg | Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) | -25.213 Percentage Change | Standard Deviation 15.389 |
| ZD4054 15 mg | Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) | 2.154 Percentage Change | Standard Deviation 41.9 |
| ZD4054 22.5 mg | Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) | -5.942 Percentage Change | Standard Deviation 34.344 |
Secondary
Total Prostate Specific Antigen (PSA) Concentration
Total Prostate Specific Antigen (PSA) concentration at Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2).
Time frame: Baseline to Day 15.
Population: All dosed patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ZD4054 10 mg | Total Prostate Specific Antigen (PSA) Concentration | 98.454 ng/ml |
| ZD4054 15 mg | Total Prostate Specific Antigen (PSA) Concentration | 62.366 ng/ml |
| ZD4054 22.5 mg | Total Prostate Specific Antigen (PSA) Concentration | 56.550 ng/ml |