Window Study of ZD4054 in Metastatic Prostate Cancer

Study Overview
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Brief Summary
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This is a prospective study in which patients with castrate-resistant prostate cancer and bone metastases will undergo imaging, donate blood, bone marrow and urine samples, and where possible primary tumour and bone metastatic tissue, before and during treatment with ZD4054, an orally active specific endothelin-A antagonist. The samples will be used primarily for biomarker studies, and it is hypothesized that these will inform on the mechanism of action of this drug. Magnetic Resonance Imaging (MRI) will be performed to evaluate emerging functional imaging endpoints as markers of early response in bone metastatic prostate cancer.

Official Title
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Assessment of the Effects of the Specific Endothelin-A Antagonist ZD4054 on Prostate Cancer Biomarkers in Patients With Castrate-resistant Metastatic Disease

Conditions
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Prostate Cancer, Metastasis

Intervention / Treatment
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* Drug: ZD4054


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histological confirmation of prostate adenocarcinoma documented evidence of bone metastasis on bone scan or MRI biochemical progression of prostate cancer surgically or medically castrate with serum testosterone ≤2.4nmol/L ECOG performance status 0 - 2 life expectancy of 6 months or more. Exclusion Criteria: radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study treatment. prior targeted cancer therapies (such as gefitinib, bevacizumab) systemic radionuclide therapy within 12 weeks of starting study treatment. current therapy, within 4 weeks of study entry with potent inhibitors of CYP3A4 (ketoconazole, itraconazole, ritonavir, indinavir, erythromycin, troleandomycin, clarithromycin, diltiazem and verapamil), inhibitors of CYPs 2D6 and 2C9 (quinidine and fluconazole), and potent P450 inducers (phenytoin, rifampicin, carbamazepine and phenobarbitone) definite or suspected personal history or family history of adverse drug reactions, or hypersensitivity to drugs that are endothelin antagonists ineligibility for MRI scanning includes standard MRI criteria (for example, metal implants such as cochlear implants, cardiac pacemakers, heart valves, aneurysm clips and metal fragments in eyes) and patients known to be allergic to gadolinium-based MRI contrast agents

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ZD4054|10mg ZD4054 daily in tablet form|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in tissue biomarkers |  | 6 weeks | 
| Changes in blood-borne biomarkers |  | 12 weeks | 
| Changes in imaging biomarkers |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castrate-resistant prostate cancer with bone metastasis