E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall aim of this study is to acquire blood, urine and tissue samples and imaging in patients with advanced prostate cancer that has spread to bone, before and during treatment with ZD4054. The samples will be used for research studies designed to elucidate the mechanism of action of this compound and to endeavour to improve therapies in this disease setting. |
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E.2.2 | Secondary objectives of the trial |
The secondary research objectives are: 1. To improve knowledge of cancer biology 2. To investigate potential biomarkers (proteins and genes) for biological resistance and response to treatment 3. To find new assays (tests) to monitor response to treatment and expedite clinical development of new drugs that target specific molecules in cancer cells 4. To discover and evaluate biomarkers that can predict for increased risk of disease relapse or progression |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histological confirmation of prostate adenocarcinoma.
2. Documented evidence of bone metastasis on radionuclide bone scan, MRI or plain radiograph
3. Biochemical progression of prostate cancer, documented while the patient is surgically or medically castrate: -Biochemical progression is defined as at least 2 stepwise increases in PSA over a period of ≥1 month with at least 14 days between each measurement irrespective of assay or laboratory. -The final PSA value must be ≥1.2ng/mL in patients who have had a radical prostatectomy and ≥1.5ng/mL in all other patients
4. Surgically or medically castrated with serum testosterone ≤2.4nmol/L (70ng/dL)
5. ECOG performance status 0 – 2.
6. Life expectancy of 6 months or more.
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E.4 | Principal exclusion criteria |
1. Radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study treatment.
2. Prior targeted cancer therapies (such as gefitinib, bevacizumab)
3. Systemic radionuclide therapy within 12 weeks of starting study treatment.
4. Current therapy, within 4 weeks of study entry with potent inhibitors on CYP3A4 (ketoconazole, itraconazole, ritinavir, indinavir, erythromycin, troleandomycin, clarithromycin, diltiazem and verapamil), inhibitors of CYPs 2D6 and 2C9 (quinidine and fluconazole), and potent P450 inducers (phenytoin, rifampicin, caramazepine and phenobarbitone).
5. Definite or suspected personal history or family history of adverse drug reactions, or hypersensitivity to drugs that are endothelin antagonists.
6. 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
7. In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease, or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measures are changes in histopathological morphology, immunohistochemistry staining patterns, genomic and DNA methylation patterns and changes in proteomics, metabonomics and imaging biomarkers before and after treatment with ZD4054. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |