E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic castration-resistant prostate cancer (mCRPC) |
carcinoma prostatico metastatico resistente alla castrazione (Metastatic Castration-resistant Prostate Cancer, mCRPC) |
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E.1.1.1 | Medical condition in easily understood language |
Prostate cancer |
carcinoma prostatico |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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 is to compare the radiographic progression-free survival(rPFS) of JNJ-56021927 in combination with abiraterone acetate (AA) plus prednisone or prednisolone (AAP) and AAP in subjects with chemotherapy-naïve mCRPC. |
L’obiettivo primario è confrontare la sopravvivenza libera da progressione all’esame radiografico (radiographic Progression-Free Survival, rPFS) di JNJ-56021927 in combinazione con abiraterone acetato (AA) più prednisone o prednisolone (AAP) rispetto ad AAP nei soggetti con mCRPC mai trattato con chemioterapia. |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the safety profile of JNJ-56021927 in combination with AAP 2. To characterize the population pharmacokinetics (PK) of JNJ-56021927 and abiraterone |
1. caratterizzare il profilo di sicurezza di JNJ-56021927 in combinazione con AAP; 2. caratterizzare la farmacocinetica (Pharmacokinetics, PK) della popolazione di JNJ 56021927 e abiraterone
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject must be a man age ≥18 years of age, inclusive - Adenocarcinoma of the prostate - Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans (visceral or lymph node disease). If lymph node metastasis is the only evidence of metastasis, it must be greater than or equal to (>=) 2 centimeter (cm) in the longest diameter - Castration-resistant prostate cancer demonstrated during continuous androgen deprivation therapy (ADT), defined as 3 rises of PSA, at least 1 week apart with the last androgen deprivation therapy (PSA) >= 2 nanogram per milliliters (ng/mL) - Participants who received a first generation anti-androgen (eg, bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after the washout period - Prostate cancer progression documented by prostate-specific antigen (PSA)according to the Prostate Cancer Clinical Trials Working Group (PCWG2)radiographic progression of soft tissues according to modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) modified based on PCWG2, or radiographic progression of bone according to PCWG2. |
1. Il soggetto deve essere un uomo di età ≥ 18 anni. 2. Adenocarcinoma della prostata. 3. Malattia metastatica documentata tramite scintigrafia ossea con tecnezio-99m (99mTc) o lesioni metastatiche evidenziate nella tomografia computerizzata (TC) o risonanza magnetica (RMI) (malattia viscerale o linfonodale). Se la metastasi linfonodale è l’unica evidenza di metastasi, questa deve avere il diametro più lungo ≥ 2 cm. 4. Carcinoma prostatico resistente alla castrazione dimostrato durante ADT continuativo, definito come 3 aumenti del PSA, a distanza di almeno 1 settimana, con l’ultimo PSA ≥ 2 ng/ml. 5. I pazienti che hanno ricevuto un anti-androgeno di prima generazione (ad es. bicalutamide, flutamide, nilutamide) devono sottoporsi a washout di almeno 6 settimane prima della randomizzazione E devono mostrare una progressione (un aumento del PSA) continua della malattia (PSA) dopo il periodo di washout. 6. Progressione del carcinoma prostatico documentata da antigene prostatico specifico (Prostate-Specific Antigen, PSA) in base al Prostate Cancer Clinical Trials Working Group (PCWG2); progressione radiografica dei tessuti molli secondo la versione 1.1 dei Criteri di valutazione di risposta nei tumori solidi (Response Evaluation Criteria in Solid Tumors, RECIST 1.1) (Allegato 1) modificata in base al PCWG2 o progressione radiografica dell’osso in base al PCWG2.
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E.4 | Principal exclusion criteria |
- Small cell or neuroendocrine carcinoma of the prostate - Known brain metastases - Prior chemotherapy for prostate cancer, except if administered in the adjuvant/neoadjuvant setting - Previously treated with ketoconazole for prostate cancer for greater than 7 days - Therapies that must be discontinued or substituted at least 4 weeks prior to randomization include the following: a) Medications known to lower the seizure threshold, b) Herbal and nonherbal products that may decrease PSA levels (example [eg], saw palmetto, pomegranate) or c) Any investigational agent - At screening need for parenteral or oral opioid analgesics (eg, codeine, dextropropoxyphene) |
1. Carcinoma prostatico neuroendocrino o a piccole cellule. 2. Note metastasi cerebrali. 3. Precedente chemioterapia per il carcinoma prostatico, eccetto se somministrata come trattamento adiuvante/neoadiuvante. 4. Precedente trattamento con chetoconazolo per il carcinoma prostatico per oltre 7 giorni. 5. Le terapie che devono essere interrotte o sostituite almeno 4 settimane prima della randomizzazione includono: • farmaci noti per l’abbassamento della soglia delle convulsioni; • prodotti fitoterapici e non fitoterapici che possono ridurre il livello del PSA (ad es. palmetto della Florida, melograno); • qualsiasi agente sperimentale. Al momento dello screening, necessità di analgesici oppioidi per via parenterale oppure orale (ad es. codeina, destropropossifene). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is radiographic progression-free survival (rPFS). |
L'endpoint primario è la sopravvivenza libera da progressione all’esame radiografico |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Radiographic progression will be assessed by Bone scan and CT/MRI scan. Bone scan will be performed within 6 weeks of randomisation. CT/MRI will be performed within 42 days of randomisation. Both Bone scans and CT/MRI will be performed on Day 1 of cycle 3, Day 1 of cycle 5 then every 3 subsequent cycles beginning at cycle 7 including EOT visit.
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La progressione radiografica sarà valutata tramite scintigrafia ossea e TC/RMI. La scintigrafia ossea verrà eseguita entro 6 settimane dalla randomizzazione. CT/MRI verranno eseguite entro 42 giorni dalla randomizzazione. Sia la scintigrafia ossea che CT/MRI saranno eseguite al Giorno 1 del Ciclo 3, Giorno 1 del Ciclo 5 e quindi ogni 3 cicli seguenti a partire dal ciclo 7 incluso la visita EOT. |
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E.5.2 | Secondary end point(s) |
1. Overall survival (OS) is defined as the time from date of randomization to date of death from any cause. 2. Time to chronic opioid use (oral opioid use for ≥3 weeks; parenteral opioid use for ≥7 days) is defined as the time from date of randomization to the first date of opioid use 3. Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy 4. Time to pain progression defined as the time from date of randomization to the first date a subject experience an increase by 2 points from baseline in the BPI-SF worst pain intensity item 3 observed at 2 consecutive evaluations ≥4 weeks apart or initiation of chronic opioids, whichever occurs first |
1. sopravvivenza globale (Overall Survival, OS) definita come il tempo dalla data della randomizzazione alla data del decesso per qualsiasi causa. 2. Tempo all’uso cronico degli oppiacei (uso di oppiacei ≥3 settimane; uso di oppiacei parenterale ≥7 giorni) definito come il tempo dalla data della randomizzazione alla prima data dell'uso di oppiacei 3. tempo all’avvio della chemioterapia citotossica definito come il tempo dalla data della randomizzazione alla data dell'avvio della chemioterapia citotossica. 4. tempo alla progressione del dolore definito come il tempo dalla data della randomizzazione alla prima data in cui un soggetto manifesta un aumento di 2 punti rispetto al basale dell'intensità peggiore del dolore al punto 3 del BPI-SF osservata a due valutazioni consecutive ≥4 settimane o l'inizio di oppiacei cronici, qualsiasi accada per primo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints 1.,2., 3. and 4 will be evaluated at EOT visit and every 3 months during the follow up phase. For Endpoint 4 the BPI-SF will be performed consecutively for 7 days starting 6 days before Day 1 of each cycle including the EOT visit and every 3 months for up to 12 months after treatment discontinuation during the follow up phase |
Endpoints 1.,2., 3. e 4 saranno valutati alla visita EOT e ogni 3 mesi nella fase di follow-up. Per l'Endpoint 4 il BPI-SF verrà eseguito in maniera consecutiva per 7 giorni a partire da 6 giorni prima del Giorno 1 di ciscun ciclo compresa la visita EOT e ogni 3 mesi fino a 12 mesi dopo l'interruzione del trattamento nella fase di follow-up. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
China |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Russian Federation |
South Africa |
Spain |
United Kingdom |
United States |
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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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EoT Visit is within 30 days after the last dose of study drug for all subjects. |
Visita di conclusione dello studio entro 30 giorni dopo l'ultima dose di farmaco dello studio per tutti i soggetti. |
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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 | 7 |
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 | 7 |