A Phase IIa. Open-label, Multicenter, Dose-escalation Study to Assess the Tolerability and Pharmacokinetics of ZD4054 (Zibotentan) Given Orally Once Daily in Subjects With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the safest dose of ZD4054 (Zibotentan)in men with prostate cancer

Conditions
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Prostatic Neoplasms, Metastases, Neoplasm

Intervention / Treatment
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* Drug: ZD4054 10 mg
* Drug: ZD4054 15 mg
* Drug: ZD4054 22.5 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZD4054 10 mg<br>1 x 10 mg oral tablets once daily | Drug: ZD4054 10 mg<br>* 1 x 10 mg oral tablets once daily<br>* Other names: Zibotentan,;|
| Experimental: ZD4054 15 mg<br>1 x 10 mg + 2 x 2.5 mg oral tablets once daily | Drug: ZD4054 15 mg<br>* 1 x 10 mg + 2 x 2.5 mg oral tablets once daily<br>* Other names: Zibotentan;|
| Experimental: ZD4054 22.5 mg<br>2 x 10 mg + 1 x 2.5 mg oral tablets once daily | Drug: ZD4054 22.5 mg<br>* 2 x 10 mg + 2 x 2.5 mg oral tablets once daily<br>* Other names: Zibotentan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Day 29. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline to Day 15. | 
| 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 | Baseline to Day 15. | 
| 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 | Baseline to Day 15. | 
| 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 | Baseline to Day 15. | 
| 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 | Baseline to Day 15. | 
| 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 | Baseline to Day 15. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, Metastatic prostate cancer, bone metastases