E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration-resistant Prostate Cancer |
Carcinoma prostatico resistente alla castrazione metastatico |
|
E.1.1.1 | Medical condition in easily understood language |
Prostate Cancer |
Cancro prostatico |
|
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076506 |
E.1.2 | Term | Castration-resistant prostate cancer |
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 |
All subprotocols To evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of investigational therapies in subjects with metastatic castration-resistant prostate cancer (mCRPC)
Subprotocol C Part 3 only To evaluate preliminary anti-tumor activity of AMG 404 monotherapy |
Tutti i sottoprotocolli Valutare la sicurezza, la tollerabilità e la dose massima tollerata (MTD) o la dose raccomandata per la fase II (RP2D) delle terapie sperimentali nei soggetti con carcinoma prostatico resistente alla castrazione metastatico (mCRPC)
Sottoprotocollo C - Parte 3 Valutare l'attività antitumorale preliminare di AMG 404 in monoterapia |
|
E.2.2 | Secondary objectives of the trial |
All subprotocols - To evaluate preliminary anti-tumor activity of investigational therapies in subjects with mCRPC - To characterize the pharmacokinetics (PK) of investigational therapies in subjects with mCRPC
Subprotocol C part 3 only - Safety: To evaluate the safety and tolerability of AMG 404 monotherapy - Efficacy: To evaluate anti-tumor activity of AMG 404 monotherapy with additional measures |
Tutti i sottoprotocolli - Valutare l'attività antitumorale preliminare delle terapie sperimentali nei soggetti con mCRPC - Caratterizzare la farmacocinetica (PK) delle terapie sperimentali nei soggetti con mCRPC
Sottoprotocollo C - Parte 3 - Sicurezza: valutare la sicurezza e la tollerabilità di AMG 404 in monoterapia - Effcacia: valutare l'attività antitumorale di AMG 404 in monoterapia con misure aggiuntive |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All Subprotocols - Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate without pure neuroendocrine differentiation or small cell features - Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist - Total serum testosterone should be <= 50 ng/dL (or 1.7 nmol/L) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 1 - Life expectancy of > 3 months
*Please refer to protocol for the full list |
Tutti i sottoprotocolli: - Soggetti con mCRPC con adenocarcinoma della prostata confermato istologicamente o citologicamente senza differenziazione neuroendocrina pura o caratteristiche a piccole cellule - Soggetti devono essere stati sottoposti a orchiectomia bilaterale o essere in terapia continua di deprivazione androgenica con un agonista o antagonista dell'ormone di rilascio delle gonadotropine - Il testosterone sierico totale deve essere <= 50 ng / dL (o 1,7 nmol / L) - Performance status dell'Eastern Cooperative Oncology Group (ECOG) di 0-1 - Aspettativa di vita > 3 mesi
*Fare riferimento al protocollo per la lista completa |
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E.4 | Principal exclusion criteria |
All Subprotocols - Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma - CNS metastases or leptomeningeal disease - Symptomatic peripheral sensory or motor neuropathy >= grade 3 - History or presence of clinically relevant CNS pathology - Confirmed history/current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy - Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials (Subprotocol A&B) / active fungal, bacterial, viral, or other infection requiring systemic therapy (Subprotocol C) within 7 days of dosing - History/evidence of inflammatory bowel disease or any other GI disorder causing chronic nausea, vomiting, or diarrhea - History of arterial or venous thrombosis within 12 months of first dose - Myocardial infarction, uncontrolled hypertension (Subprotocol A&C), unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months (Subprotocol A&B) / within 6 months (Subprotocol C) of first dose of AMG 160
*Please refer to protocol for the full list |
Tutti i sottoprotocolli: - Reperto patologico compatibile con carcinoma neuroendocrino della prostata a piccole cellule puro o qualsiasi altra istologia diversa dall'adenocarcinoma - metastasi del sistema nervoso centrale o malattia leptomeningea - Neuropatia sensoriale o motoria periferica sintomatica >= grado 3 - Anamnesi o presenza di patologia del SNC clinicamente rilevante - Anamnesi confermata/malattia autoimmune in corso o altre malattie che hanno portato a immunosoppressione permanente o che richiedono una terapia immunosoppressiva permanente - Presenza di infezioni fungine, batteriche, virali o di altro tipo che richiedono antimicrobici e.v.(sottoprotocollo A e B)/infezioni fungine attive, batteriche, virali o di altro tipo che richiedono terapia sistemica (sottoprotocollo C) entro 7 giorni dalla somministrazione - Anamnesi/evidenza di malattia infiammatoria intestinale o qualsiasi altro disturbo GI che causa nausea, vomito o diarrea cronici - Anamnesi di trombosi arteriosa o venosa entro 12 mesi dalla prima dose - Infarto del miocardio, ipertensione incontrollata (sottoprotocollo A e C), angina instabile, aritmia cardiaca che richiede farmaci e/o insufficienza cardiaca congestizia sintomatica (New York Heart Association > classe II) entro 12 mesi (sottoprotocollo A e B)/entro 6 mesi (sottoprotocollo C) dalla prima dose di AMG 160
*Fare riferimento al protocollo per la lista completa |
|
E.5 End points |
E.5.1 | Primary end point(s) |
All subprotocols - dose-limiting toxicities (DLTs) - treatment-emergent and treatment-related adverse events - changes in vital signs, and clinical laboratory tests
Subprotocol C Part 3 - objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications - circulating tumor cell (CTC) response (CTC0 and CTC conversion) - prostate-specific antigen (PSA) response |
Tutti i sottoprotocolli: - tossicità dose-limitanti (DLT) - eventi avversi emersi durante il trattamento e correlati al trattamento - variazioni dei parametri vitali e delle analisi cliniche di laboratorio
Sottoprotocollo C - Parte 3 - risposta oggettiva secondo i criteri RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 con modifiche del Prostate Cancer Working Group 3 (PCWG3) - risposta delle cellule tumorali circolanti (CTC) (conversione CTC0 e CTC) - risposta all'antigene prostatico specifico (PSA) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of AMG 160 (or AMG 404 in Parts 1 and 2 and at least 1 dose of AMG 404 in Part 3 - Subprotocol C). |
L'analisi di tutti gli endpoint, salvo diversa indicazione, sarà condotta sul set di analisi della sicurezza definito come tutti i soggetti che sono stati arruolati e ricevono almeno 1 dose di AMG 160 (o AMG 404 nelle parti 1 e 2 e almeno 1 dose di AMG 404 nella parte 3 - Sottoprotocollo C). |
|
E.5.2 | Secondary end point(s) |
All subprotocols - objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications - circulating tumor cell (CTC) response (CTC0 and CTC conversion) - prostate-specific antigen (PSA) response - duration of response (CTC, PSA, conventional radiographic) - overall survival (OS) - progression-free survival (radiographic, PSA, clinical) - time to progression (radiographic, PSA) - time to subsequent therapy
*Please refer to protocol for the full list |
Tutti i sottoprotocolli: - risposta oggettiva secondo i criteri RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 con modifiche del Prostate Cancer Working Group 3 (PCWG3) - risposta delle cellule tumorali circolanti (CTC) (conversione CTC0 e CTC) - risposta all'antigene prostatico specifico (PSA) - durata della risposta (CTC, PSA, radiografica convenzionale) - sopravvivenza globale (OS) - sopravvivenza libera da progressione (radiografica, PSA, clinica) - tempo alla progressione (radiografica, PSA) - tempo alla successiva terapia
*Fare riferimento al protocollo per la lista completa |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of AMG 160 (or AMG 404 in Parts 1 and 2 and at least 1 dose of AMG 404 in Part 3 - Subprotocol C). |
L'analisi di tutti gli endpoint, salvo diversa indicazione, sarà condotta sul set di analisi della sicurezza definito come tutti i soggetti che sono stati arruolati e ricevono almeno 1 dose di AMG 160 (o AMG 404 nelle parti 1 e 2 e almeno 1 dose di AMG 404 nella parte 3 - Sottoprotocollo C). |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety, tolerability, PK, PD and efficacy - dose exploration and dose expansion |
Sicurezza, tollerabilità, PK, PD ed efficacia - esplorazione della dose ed espansione della dose |
|
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 | Information not present in EudraCT |
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 |
Australia |
Canada |
United States |
|
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
|
LSLV - The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), following any additional parts in the study (eg, long-term follow-up, additional antibody testing), as applicable. |
LSLV - La data di fine studio è definita come la data in cui l'ultimo soggetto tra tutti i siti viene valutato o riceve un intervento per la valutazione nello studio (ovvero, l'ultima visita dell'ultimo soggetto), a seguito di eventuali parti aggiuntive dello studio (ad es. follow-up a lungo termine, test anticorpali aggiuntivi), se applicabile. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |