E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Castration resistant metastatic prostate cancer progressing after docetaxel based treatment |
Cancro della prostata in fase metastatica e resistente alla castrazione in progressione dopo terapia con docetaxel |
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E.1.1.1 | Medical condition in easily understood language |
Advanced prostate cancer resistant to previous chemotherapy with docetaxel |
Cancro della prostata in fase metastatica e resistente alla castrazione in progressione dopo terapia con docetaxel |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 primary objective of the trial is to evaluate the activity of cabazitaxel in terms of improvement of progression free survival (PFS, defined as a composite endpoint) after 3 months of treatment in elderly patients progressing after a previous docetaxel-based chemotherapy |
L'obiettivo primario dello studio consiste nel valutare l'attività del cabazitaxel in termini di miglioramento della sopravvivenza libera da malattia (PFS, definita come endpoint) dopo 3 mesi di trattamento in pazienti anziani in progressione dopo terapia con docetaxel |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: biochemical response, overall survival (OS), treatment toxicity and geriatric assessment |
Obiettivi secondari sono: valutazione della risposta biochimica, della sopravvivenza globale (OS), della tossicità e dell’impatto della terapia sullo stato funzionale dell’anziano |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Metastatic castration-resistant disease with documented clinical (imaging) and/or biochemical progression (PSA increasing* values) during or after a previous docetaxel-based chemotherapy; •Testosterone level within castration range (levels <50 ng/dl); •Life expectancy ≥ 3 months; •G8 Score ≥8 and ≤14 ; •ANC ≥ 1.5 x 109/L; PLT ≥ 100 x 109/L; Hb ≥10 g/dl; •Serum total bilirubin ≤ UNL; •AST/SGOT and ALT/SGPT ≤1.5 times UNL; •ALAT and creatinine ≤1.5 times UNL (in case of limit values of serum creatinine, creatinine clearance calculated by CKD-EPI formula should be ≥60 ml/min); •Patients must be accessible for treatment and follow up; •Age ≥ 70 years. *at least two consecutive rises in PSA (with an increase in the absolute-value of at least 2 ng/ml), to be documented over a reference value. PSA measures should be taken at least 2 week apart. In the case the second PSA measure was less than the first increase, a third confirmatory measure (this measure has to be greater than the first PSA rise) is required to be taken.
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• Malattia metastatica resistente alla castrazione documentata in progressione clinico-strumentale e/o biochimica (incremento dei valori* del PSA) durante o dopo una precedente chemioterapia a base di docetaxel; • Livello di testosteronemia indicativo di una situazione di castrazione (< 50 ng/dl); • Aspettativa di vita ≥ 3 mesi; • G8 Score ≥8 e ≤14 ; • Conta dei neutrofili ≥ 1.5 x 109/L; conta delle piastrine ≥ 100 x 109/L; Hb ≥10 g/dl; • Bilirubina totale sierica ≤ al limite massimo del range di normalità; • AST/SGOT e ALT/SGPT ≤1.5 volte il limite massimo del range di normalità; • Creatinina sierica ≤1.5 volte il limite massimo del range di normalità; (nel caso di valori limite della creatinina sierica la clearance della creatinina calcolata con la formula CDK-EPI dovrà essere > 60 ml/min; • Accessibilità dei pazienti al trattamento ed al follow up; • Età ≥ 70 anni. *dovranno essere documentati almeno due incrementi consecutivi del PSA al di sopra del valore di riferimento (con un incremento in assoluto di almeno 2 ng/ml). Le determinazioni del PSA dovranno essere effettuate a distanza di almeno 2 settimane. Nel caso in cui la seconda determinazione del PSA fosse inferiore rispetto alla prima sarà necessaria una terza determinazione per conferma (questa determinazione dovrà documentare un valore del PSA superiore rispetto al primo incremento).
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E.4 | Principal exclusion criteria |
•Age ≥ 85; •G8 score < 8 or > 14 •Ventricular injection fraction < 50%; •Any of concomitant serious respiratory or cardiovascular diseases; •Active coronary artery disease, uncontrolled hypertension; •Any contraindications for administration of corticosteroids or premedication used for cabazitaxel infusion; •History of severe hypersensitivity reaction (≥grade 3) to docetaxel and polysorbate 80 containing drugs; •Significant neurological or psychiatric disorders; •Previous Isotope treatment within 28 days prior to enrolment; •Concomitant treatment with other experimental drug, ketoconazole or itraconazole or any other anti-cancer therapy (except for LHRH agonists/antagonists). Other anticancer therapy stopped at least 28 days prior enrolment; •Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus); •Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a two weeks wash-out period is necessary for patients who are already on these treatments); •ECOG performance status >2
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• Età ≥ 85 anni; • G8 score < 8 o > 14 • Frazione di eiezione ventricolare < 50%; • Qualsiasi patologia respiratoria o cardiovascolare grave; • CAD (arteriopatia coronarica) attiva, ipertensione arteriosa non controllabile; • Qualsiasi controindicazione per la somministrazione di corticosteroidi o farmaci utilizzati nella premedicazione per l’infusione del cabazitaxel; • Anamnesi positiva per severa reazione allergica (> a grado 3) al docetaxel ed a farmaci contenenti polisorbato 80; • Significativi disordini neurologici o psichiatrici; • Pregresso trattamento con isotopo (non meno di 28 giorni prima dell’arruolamento); • Trattamento concomitante con altri farmaci sperimentali, ketoconazolo od itraconazolo o qualsiasi altra terapia antineoplastica (eccetto LHRH agonisti/antagonisti). Altre terapie antineoplastiche dovranno essere state concluse almeno 28 giorni prima dell’arruolamento; • Malattie gravi o situazioni patologiche non controllabili (incluso il diabete mellito scompensato); • Trattamento concomitante o programmato con forti inibitori del citocromo P450 3A4/5 (sarà necessario un periodo di “wash-out” di almeno due settimane per i pazienti eventualmente già in trattamento con tali farmaci); ECOG performance status >2. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is a composite progression free survival (PFS) endpoint defined as the occurrence of any of the following events: tumor progression based on RECIST criteria; bone progression when 2 or more new lesions; pain progression based on PPI test; death from of any cause.
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Come endpoint primario viene considerata la sopravvivenza libera da progressione (PFS),definita come il manifestarsi di uno dei seguenti eventi: progressione tumorale basata sui criteri RECIST; progressione ossea, in presenza di 2 o più nuove lesioni; progressione del dolore in base al test PPI; morte per qualsiasi causa |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Baseline - Every 3 cycles (15 weeks) - At the end of the treatment - During the follow-up phase every 3 months |
- Basale - Ogni 3 cicli (15 settimane) - Alla fine del trattamento - Durante il follow-up ogni tre mesi |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: biochemical Response (defined as a reduction from baseline PSA level of at least 50%, maintained for at least 3 weeks); ORR by Recist criteria V1.1; overall survival (OS); close monitoring of toxicity using the NCICTC- AE version 4.03; evaluation of geriatric assessment using the Minimal Data Set (MDS) according to the Elderly Task Force (ETF) EORTC: - Charlson comorbidity index; - G8 geriatric assessment screening tool; - Instrumental activities of daily living (IADL); - Social situation.
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Come end points secondari vengono considerati: risposta biochimica (definita come una riduzione del valore del PSA di almeno il 50%, mantenuta per almeno 3 settimane); ORR secondo i criteri Recist; sopravvivenza globale (OS); stretto monitoraggio della tossicità utilizzando i criteri della NCICTC- AE version 4.03; valutazione geriatrica utilizzando il Minimal Data Set (MDS) secondo l'Elderly Task Force (ETF) EORTC: - Charlson comorbidity index; - G8 geriatric assessment screening tool; - Instrumental activities of daily living (IADL); - Social situation.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Biochemical Response (every 10 weeks/2 cycles); ORR by Recist criteria (every 15 weeks); overall survival (OS); close monitoring of toxicity using the NCICTC- AE version 4.03; evaluation of geriatric assessment (baseline, during treatment, end of treatment) using the Minimal Data Set (MDS) according to the Elderly Task Force (ETF) EORTC: - Charlson comorbidity index; - G8 geriatric assessment screening tool; - Instrumental activities of daily living (IADL); - Social situation.
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Risposta biochimica (ogni 10 settimane/due cicli); ORR in base ai criteri Recist (ogni 15 settimane); stretto monitoraggio della tossicità utilizzando la NCICTC - AE version 4.03; valutazione geriatrica (al basale, durante il trattamento, alla fine del trattamento) usando il Minimal Data Set dell'Elderly Task Force (ETF) EORTC: - Charlson comorbidity index; - G8 geriatric assessment screening tool; - Instrumental activities of daily living (IADL); - Social situation.
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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 | No |
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) | 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 | 7 |
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 | No |
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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LVLS |
Ultima visita dell'ultimo paziente |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |