E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hormone refractory metastatic prostate cancer |
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MedDRA Classification |
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 |
To determine the efficacy (as measured by tumor response) of valproic acid given orally to patients with hormone refractory metastatic prostate cancer after first line chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
To describe the time to progression and toxic effects of valproic acid in patients with hormone refractory metastatic prostate cancer. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. signed written informed consent 2. men aged 18 years or older 3. histologically proven metastatic hormone refractory prostatic adenocarcinoma, with progression after standard 1st line chemotherapy (only docetaxel+prednisone). The progression is defined: progression according RECIST criteria or evidence of PSA progression. Minimum evidence of progression is a 25% increase over a reference value of PSA (20ng/mL), provided that the increase is > 5 ng/mL. The first increase in PSA should occur at a minimum of one week from the reference value. This increase should then be confirmed by a second increase in PSA at least 1 week later (Bubley, 1999). 4. patients with measurable or non-measurable disease as defined in the RECIST criteria: At least one site of disease must be unidimensionally measurable as follows: X-ray, physical exam > 20 mm } N.B. Most hospitals have spiral CT scanning Spiral CT scan > 10 mm } equipment – check with your radiology department. Non-spiral CT scan > 20 mm } All radiology studies must be performed within 28 days prior to registration 5. ECOG PS 0 – 1 at study entry 6. at least 4 weeks must have elapsed since the last surgery, radiotherapy and/or chemotherapy before study entry 7. complete recovery from prior surgery, and/or reduction of all adverse events to grade 1 from previous systemic therapy or radiotherapy 8. no concurent treatment with experimental drugs was allowed. 9. no concurrent chemotherapy. Corticosteroids and bisphophonates are permitted if they were admistered more than 2 months before study entry in the same dose and route of application. 10. patients with surgical castration or patients without surgical castration must have a serum testosterone level less than 50ng/ml before study entry and to continue on LHRH agonist therapy 11. adequate renal function defined as creatinine clearance > 60ml/min 12. adequate liver function defined by normal total bilirubin level and ALT, AST < 2,0 ULN 13. adequate hematologic function defined by ANC > 1500/mm3, platelet count > 100 000/mm3 and hemoglobin level > 9g/dl. 14. normal blood coagulation tests: INR, fibrinogen, PTT, bleeding time 15. serum albumin level > 34g/l 16. life expectancy more than 3 months 17. absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
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E.4 | Principal exclusion criteria |
1. inability to absorb medication e.g. malabsorption syndrome 2. hepatic porphyria 3. acute or chronic hepatitis (positivity HbsAg, antiHCV and/or LFT`s see also inclusion criteria) 4. hypersensitivity to valproic acid 5. personal or familial history of severe drug induced hepatitis 6. grade 3-4 infection without neutropenia 7. known CNS metastasis 8. Any concurrent malignancy other than non-melanoma skin cancer, no other cancer in past 5 years. 9. Serious concomitant systemic disorders or diseases incompatible with the study (at the discretion of investigator ) 10. systemic lupus erythematosis
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate (according to Bubleys criteria) |
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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 | No |
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 | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | Yes |
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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6 months after the last administration of valproic acid (Everiden) in 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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |