E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with histologically proven prostate adenocarcinoma (non metastatic) |
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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 | 10029096 |
E.1.2 | Term | Neoplasm prostate |
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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 |
1) Assessment of the pathologic response (percentage) after 4 cycles of neoadjuvant chemotherapy based on Docetaxel 75 mg/mq plus prednison 5 mg BID 2) Evaluation of the PSA response rate at every cycle 3) Determination of the Down- staging percentage 4) Evaluation of chemotherapy toxicity 5) Evaluation of proteins involved in cell cycle regulation and in apoptosis (p53, p21, Bcl2 e Bax) and of genes involved in prediction of tumour response to taxanes (Chfr, Snk/Plk2, Filamine A-B-C, YPEL) both on the biopsy at the diagnosis and after the neoadjuvant therapy with taxotere, in order to provide to the physician objective parameters to assess the probability of clinical response in each patient |
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the disease free survival (clinic or serologic) after two years of neoadjuvant chemotherapy based on Docetaxel following surgery and the hormone therapy in the locally advanced prostate adenocarcinoma (to determine the time of arising of hormone-refractoriness) 2) Determine the overall survival 3) Evaluate the time of treatment failure 4) Measure the ratio of PSA normalization 5) Quality of life analysis 6) Evaluate the variations of cromogranin A concentrations 7) Analysis of the role of ERK1/2 in the acquired resistance to taxotere, in relation to the expression of the above mentioned proteins and EGFR. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Histologically proven prostate adenocarcinoma Er MRI to assess the disease extension and the prostate volume (endo-rectal), eventually Total PSA ≥ 20 ng/ml e ≤ 50 ng/ml and patients with PSA ≥ 50 ng/ml excluded. Other criteria described by nomograms findable on the website http//www.nomograms.org; Gleason score 8-10 by prostatic mapping T3a clinical staging Eventual presence of locoregional lynphonodal Cromogranin A Testosteron evaluation Bone scan if it suspects skeletal metastasis Coline TC-PET (to execute TC-PET to the beginning and the end of the treatment to estimate the pathologic staging; naturally to repeat the TC-PET to the end of treatment if to the beginning the TC-PET turned out positive) Age years:18 ≥ ≤ 75 Estimated life expectancy of at least 6 months Performance status ≤ 2 Adeguate bone marrow, renal and liver function: neutrophles count ≥ 1,500/mm3; platelets ≥ 100,000/mm3; haemoglobin ≥ 10 g/dL; bilirubin <1.5 times above normal ranges; AST/ALT <1.5 times above normal ranges; creatinine ≥ 1.5 mg/dl. Written informed consent Absence of anypsychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule The patients must be all making radical surgery in the case of positive margine they should make adjuvant radiotherapy. |
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E.4 | Principal exclusion criteria |
Distant metastases Active uncontrolled infections requiring intravenous antibiotic therapy Active peptic ulcer, uncontrolled diabetes mellitus or other controindications for cortisonic therapy Presence of any clinically significant cardiac arrhythmia, congestive heart failure (LVEF < 40%), myocardial infaction, unstable angina or coronary artery bypass graft in the previous six months Other severe or chronic medical or psychiatric condition that would impart, in the judgement of the investigator, excess risk associated with study participation or would make the patient inappropriate for entry into this study Other concomitant malignancies (other than treated carcinomas of the skin different from melanoma or other malignancies treated with curative intent) and no evidence of disease since, at least, five years Patients with extension extracapsulare disease at first diagnosis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of the pathologic response (percentage) after 4 cycles of neoadjuvant chemotherapy based on Docetaxel 75 mg/mq plus prednison 5 mg BID |
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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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
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) | 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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |