E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Hormone-Naive Prostate Cancer (mHNPC) |
Carcinoma metastatico della prostata di nuova diagnosi non sottoposto a precedente terapia ormonale |
|
E.1.1.1 | Medical condition in easily understood language |
Prostate Cancer |
Tumore alla prostata |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029002 |
E.1.2 | Term | Neoplasm of the prostate |
E.1.2 | System Organ Class | 100000004864 |
|
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 whether ZYTIGA in combination with low-dose prednisone and ADT is superior to ADT alone in improving survival in subjects with mHNPC with high risk prognostic factors. |
L’obiettivo principale consiste nel determinare se ZYTIGA in combinazione con prednisone a basso dosaggio e ADT (Androgen Deprivation Therapy, ADT) sia superiore alla sola ADT nel migliorare le aspettative di vita in soggetti affetti da mHNPC ormonale (Metastatic Hormone-Naïve Prostate Cancer, mHNPC) con fattori prognostici ad alto rischio. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the clinically relevant improvements as well as the safety of ZYTIGA plus low-dose prednisone and ADT compared to ADT alone. •To identify microRNA (miRNA) and mRNA profiles predictive of ZYTIGA response or resistance. |
Gli obiettivi secondari consistono nel valutare i miglioramenti rilevanti dal punto di vista clinico, oltre alla sicurezza di ZYTIGA più prednisone a basso dosaggio e ADT rispetto alla sola ADT e nell’identificare i profili di microRNA (miRNA) e mRNA predittivi della risposta o resistenza di ZYTIGA in questa popolazione di pazienti. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology 2. Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography or magnetic resonance imaging scan 3. Two of the following high-risk prognostic factors: Gleason score of >=8; presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis 4. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2 5. Adequate hematologic, hepatic, and renal function 6. Agrees to protocol-defined use of effective contraception |
1.Diagnosi recente di carcinoma prostatico metastatico entro 3 mesi prima della randomizzazione con adenocarcinoma prostatico confermato mediante esame istologico o citologico, senza differenziazione neuroendocrina o istologia a piccole cellule. 2.Malattia metastatica distante documentata da scintigrafia ossea positiva o lesioni metastatiche evidenziate da TC o RMI. 3.Due dei seguenti fattori prognostici ad alto rischio: -punteggio di Gleason ≥ 8; -presenza di 3 o più lesioni alla scintigrafia ossea; -presenza di metastasi viscerali misurabili (escluse patologie dei linfonodi) (RECIST 1.1). 4.Stato prestazionale secondo l’Eastern Cooperative Oncology Group (ECOG) di grado 0, 1 o 2 5.Adeguata funzionalità ematologica, epatica e renale 6.Accettazione di contraccezione efficace come da Protocollo |
|
E.4 | Principal exclusion criteria |
1. Active infection or other medical condition that would make prednisone use contraindicated 2. Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day 3. Pathological finding consistent with small cell carcinoma of the prostate 3. Known brain metastasis 4. Any prior pharmacotherapy, radiation therapy, or surgery with curative intent for metastatic prostate cancer (the following exception is allowed: up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or orchiectomy with or without concurrent anti-androgens prior to patients randomization is permitted; patients may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered prior to randomization) 5. Radiation or surgical therapy could not have been initiated 4 weeks after the start of ADT or orchiectomy 6. Uncontrolled hypertension (systolic blood pressure >=160 mmHg or diastolic BP >=95 mmHg; patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment) 7. Active or symptomatic viral hepatitis or chronic liver disease 8. History of adrenal dysfunction 9. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline 10. Atrial fibrillation, or other cardiac arrhythmia requiring pharmacotherapy 11. Other malignancy (within 5 years), except non-melanoma skin cancer 12. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational study 13. Any condition or situation which, in the opinion of the investigator, would put the patient at risk, may confound study results, or interfere with the patient's participation in this study |
1. Infezione attiva o altra patologia medica che renderebbe controindicato l’impiego di prednisone. 2. Qualsiasi patologia medica cronica che necessita di una dose sistemica maggiore di corticosteroide rispetto ai 5 mg/die di prednisone. 3. Risultato patologico che evidenzi un carcinoma prostatico a piccole cellule. 4. Metastasi cerebrale nota. 5. Qualsiasi terapia farmacologica, radioterapia o intervento chirurgico precedente con intento curativo di carcinoma prostatico metastatico. Sono consentite le seguenti eccezioni: sono consentiti fino a 3 mesi di ADT con agonisti LHRH o orchiectomia con o senza antiandrogeni concomitanti prima della randomizzazione dei soggetti; I soggetti possono avere effettuato radioterapia con intento palliativo o terapia chirurgica per trattare i sintomi della patologia metastatica (per esempio rischio di compressione vertebrale o sintomi ostruttivi) se somministrate prima della randomizzazione. Non sono ammesse radioterapia o chirurgia 4 settimane dopo l’inizio dell’ADT o dopo l’orchiectomia. 6. Ipertensione non controllata (pressione sistolica ≥ 160 mmHg o diastolica ≥ 95 mmHg). Sono ammessi i soggetti con anamnesi di ipertensione, purché la pressione sanguigna sia controllata da un trattamento anti-ipertensivo. 7. Epatite virale attiva o sintomatica o patologia epatica cronica. 8. Anamnesi di disfunzione surrenale. 9. Cardiopatia clinicamente significativa con evidenza di infarto miocardico, o eventi trombotici arteriosi manifestatisi negli ultimi 6 mesi, angina grave o instabile, o cardiopatia di classe II-IV della New York Heart Association (NYHA) o misurazione della frazione di eiezione basale < 50%. 10. Fibrillazione atriale o altra aritmia cardiaca che necessiti di farmacoterapia. 11. Altra patologia maligna (nell’arco di 5 anni), eccetto il tumore cutaneo non melanoma. 12. Somministrazione di una procedura terapeutica o chirurgica invasiva sperimentale (esclusa la castrazione chirurgica) entro 30 giorni dal Ciclo 1 Giorno 1 o attualmente arruolati in uno studio sperimentale. 13. Qualsiasi patologia o situazione che, a giudizio dello sperimentatore, metterebbe il soggetto a rischio, potrebbe confondere i risultati dello studio o interferire con la partecipazione del soggetto al presente studio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival |
Sopravvivenza |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Randomization up to the time of death from any cause |
Dalla randomizzazione al decesso per qualsiasi causa |
|
E.5.2 | Secondary end point(s) |
1) Radiographic progression-free survival 2) Time to next subsequent therapy for prostate cancer 3) Time to initiation of chemotherapy 4) Time to prostate specific antigen progression 5) Time to next skeletal-related event |
1) Sopravvivenza senza progressione di malattia al riscontro radiografico 2) Tempo fino alla successiva terapia per carcinoma prostatico 3) Tempo fino all’inizio di chemioterapia 4) Tempo fino alla progressione dell’antigene prostatico specifico 5) Tempo al successivo eventi che interessa lo scheletro |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1From randomization, up to disease progression or death from any cause (up to Month 60) 2, 3 & 4) From randomization to time to the occurrence of each event 5) From randomization to time to the occurrence of one of the following: clinical fracture, spinal cord compression, palliative radiation to bone, surgery to bone |
1 Dalla randomizzazione fino a progressione di malattia o morte per qualsiasi causa (fino al mese 60) 2,3 e 4 Dalla randomizzazione fino all’accadere di qualsiasi evento 5 Dalla randomizzazione fino all’accadere di uno dei seguenti: frattura, compressione spinale, radiazione palliativa alle ossa, chirurgia alle ossa |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | Yes |
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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
antagonisti LHRH o orchiectomia |
LHRH antagonists or ochiectomy |
|
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 123 |
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 |
Brazil |
Canada |
Chile |
China |
Colombia |
Israel |
Japan |
Korea, Democratic People's Republic of |
Malaysia |
Mexico |
New Zealand |
Peru |
Russian Federation |
Singapore |
South Africa |
Turkey |
Ukraine |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 66 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 66 |
E.8.9.2 | In all countries concerned by the trial days | 0 |