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 (mCRPC) |
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E.1.1.1 | Medical condition in easily understood language |
Prostate Cancer |
Cancro alla Prostata |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | 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 |
- Radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG3) [Time Frame: Approximately 2 years] - Overall Survival (OS) [Time Frame: Approximately 3 years] |
- Sopravvivenza libera da progressione radiologica (rPFS) in base ai criteri di PCWG3 [Time Frame: circa 2 anni] - Sopravvivenza Globale (OS) [Time Frame: circa 3 anni] |
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E.2.2 | Secondary objectives of the trial |
- Objective Response Rate (ORR) per Prostate Cancer Working Group (PCWG3) [Time Frame: Approximately 3 years] - Duration of response (DOR) per Prostate Cancer Working Group (PCWG3) [Time Frame: Approximately 3 years] - PSA Response Rate (PSA-RR) [Time Frame: Approximately 3 years] - Time to Response per PCWG3 (TTR-PCWG3) assessed by BICR [Time Frame: Approximately 3 years] - Time to pain progression [Time Frame: Approximately 3 years] - Time to PSA Progression (TTP-PSA) [Time Frame: Approximately 3 years] - Incidence of AEs (Adverse Events) [Time Frame: Approximately 3 years] - Incidence of SAEs ( Serious Adverse Events) [Time Frame: Approximately 3 years] |
- Tasso di risposta obiettiva (ORR) in base ai criteri PCWG3 [Time Frame: circa 3 anni] - Durata della risposta (DOR) in base ai criteri PCWG3 [Time Frame: circa 3 anni] - Tasso di risposta del PSA (PSA-RR) [Time Frame: circa 3 anni] - Tempo alla risposta in base ai criteri CWG3 (TTR-PCWG3) determinato in base a BICR [Time Frame: circa 3 anni] - Tempo alla progressione del dolore [Time Frame: circa 3 anni] - Tempo alla progressione del PSA (TTP-PSA) [Time Frame: circa 3 anni] - Incidenza di eventi avversi (AE) [Time Frame: circa 3 anni] - Incidenza di eventi avversi seri (SAE) [Time Frame: circa 3 anni] |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologic confirmation of adenocarcinoma of the prostate and evidence of stage IV disease • Must have ECOG performance status 0-1 • Documented prostate cancer progression per PCWG3 criteria within 6 months prior to screening • Ongoing androgen deprivation therapy (ADT) with a gonadotropinreleasing hormone (GnRH) analogue or bilateral orchiectomy • Participants who are chemotherapy-naive and received 1 to 2 prior second generation hormonal therapies • Sufficient tumor sample from fresh or archival tumor tissue obtained no more than 1 year prior to enrollment, from a metastatic lesion or primary tumor lesion that has not been previously irradiated |
-Conferma istologica di adenocarcinoma della prostata ed evidenza di malattia allo stadio IV -Avere performance status ECOG 0-1 -Progressione documentata del carcinoma prostatico secondo i criteri del Prostate Cancer Clinical Trials Working Group (PCWG3) nei 6 mesi precedenti lo screening -Terapia di deprivazione androgenica (ADT) in corso con un analogo dell’ormone di rilascio delle gonadotropine (GnRH) o orchiectomia bilaterale -Partecipanti naïve alla chemioterapia e che hanno ricevuto almeno 1 ma non più di 2 manipolazioni ormonali di seconda generazione -Un numero sufficiente di campioni di tessuto tumorale ricavato da una biopsia fresca o tessuto tumorale ricavati entro 1 anno prima della data di arruolamento da una lesione tumorale metastatica o da una lesione tumorale primaria che non sia stata precedentemente irradiata. |
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E.4 | Principal exclusion criteria |
• Participants with active brain metastases • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured • Participants with an active, known, or suspected autoimmune disease • Participants requiring systemic treatment with corticosteroids (> 10mg daily prednisone equivalent) or other immunosuppressive medications • Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways • Prior treatment with docetaxel or another chemotherapy for metastatic castration resistant prostate cancer |
• Participants with active brain metastases • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured • Participants with an active, known, or suspected autoimmune disease • Participants requiring systemic treatment with corticosteroids (> 10mg daily prednisone equivalent) or other immunosuppressive medications • Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways • Prior treatment with docetaxel or another chemotherapy for metastatic castration resistant prostate cancer |
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - rPFS for all randomized participants is the time between randomization and the first date of documented progression or death due to any cause, whichever occurs first. The radiographic progression will be assessed by Blinded Independent Central Review (BICR) per PCWG3. The rPFS will be censored at the last tumor assessment up to the start of subsequent systemic cancer therapy for those without progression. 2 - OS for all randomized participants is the time between randomization and the date of death from any cause. For participants who are alive, their survival time will be censored at the last date that they were known to be alive. OS will be censored for participants at the date of randomization if they had no follow-up. |
1 - La rPFS per tutti i partecipanti randomizzati è il tempo tra la randomizzazione e la prima data di progressione documentata o il decesso per qualsiasi causa, a seconda di quale evento si verifichi prima. La progressione radiologica sarà valutata mediante revisione centrale indipendente in cieco (BICR) in base ai criteri PCWG3. La rPFS sarà censurata all’ultima valutazione del tumore fino all’inizio della successiva terapia antitumorale sistemica per coloro che non mostrano progressione. 2 - L’OS per tutti i partecipanti randomizzati è il tempo tra la randomizzazione e la data del decesso per qualsiasi causa. Per i partecipanti che sono in vita, il tempo di sopravvivenza sarà censurato all’ultima data in cui è noto che fossero in vita. L’OS sarà censurata per i partecipanti alla data di randomizzazione, in assenza di follow-up. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During treatment and post treatment follow up until progression, death or lost of follow up |
Durante il follow-up di trattamento e post-trattamento fino alla progressione, morte o perdita del follow-up |
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E.5.2 | Secondary end point(s) |
- Objective Response Rate per PCWG3 (ORR-PCWG3) is the proportion XML File Identifier: 8Gzeo0dJbPBTD+JxkqUDHJAJzWI=Page 16/34 of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among randomized participants who have measurable disease at baseline. The BOR is defined as the best response designation, as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression per PCWG3 or the date of subsequent systemic cancer therapy, whichever occurs first. For participants without documented progression or subsequent systemic cancer therapy, all available response assessments will contribute to the BOR assessment. - Time to Response per PCWG3 (TTR-PCWG3) is the time from randomization to the date of the first documented CR or PR per PCWG3, as determined by BICR. - Duration of Response per PCWG3 (DOR-PCWG3) is the time between the date of first response (CR/PR per PCWG3) to the date of first documented radiographic progression per PCWG3, as determined by BICR, or death due to any cause. Participants who neither progress nor die will be censored at the last tumor assessment up to the start of subsequent systemic cancer therapy. - PSA Response Rate (PSA-RR) is the proportion of randomized participants with a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result. A second consecutive value obtained 3 or more weeks later is required to confirm the PSA response. - PSA response will be calculated for all participants with PSA values at baseline and at least one post baseline assessment. - Time to PSA Progression (TTP-PSA) is the time between randomization to the date of PSA progression per PCWG3 in randomized participants. For participants with an initial PSA decline from baseline, the date of PSA progression is the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from the nadir are documented and confirmed by a second consecutive PSA value at least 3 weeks later. For participants with no PSA decline from baseline, the date of PSA progression is the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from baseline are documented beyond Week 13. TTPPSA will be censored at the date of last PSA evaluation prior to the start of subsequent systemic cancer therapy. The time will be censored at the date of randomization for participants with no post-baseline PSA evaluation. - Overall safety and tolerability will be measured by the incidence of AEs, SAEs, AEs leading to discontinuation, immune-mediated AEs, select AEs, deaths, and laboratory abnormalities and changes from baseline. - Median time to pain progression as assessed by Brief Pain Inventory-Short Form (BPI-SF) |
- Objective Response Rate per PCWG3 (ORR-PCWG3) is the proportion XML File Identifier: 8Gzeo0dJbPBTD+JxkqUDHJAJzWI=Page 16/34 of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among randomized participants who have measurable disease at baseline. The BOR is defined as the best response designation, as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression per PCWG3 or the date of subsequent systemic cancer therapy, whichever occurs first. For participants without documented progression or subsequent systemic cancer therapy, all available response assessments will contribute to the BOR assessment. - Time to Response per PCWG3 (TTR-PCWG3) is the time from randomization to the date of the first documented CR or PR per PCWG3, as determined by BICR. - Duration of Response per PCWG3 (DOR-PCWG3) is the time between the date of first response (CR/PR per PCWG3) to the date of first documented radiographic progression per PCWG3, as determined by BICR, or death due to any cause. Participants who neither progress nor die will be censored at the last tumor assessment up to the start of subsequent systemic cancer therapy. - PSA Response Rate (PSA-RR) is the proportion of randomized participants with a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result. A second consecutive value obtained 3 or more weeks later is required to confirm the PSA response. - PSA response will be calculated for all participants with PSA values at baseline and at least one post baseline assessment. - Time to PSA Progression (TTP-PSA) is the time between randomization to the date of PSA progression per PCWG3 in randomized participants. For participants with an initial PSA decline from baseline, the date of PSA progression is the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from the nadir are documented and confirmed by a second consecutive PSA value at least 3 weeks later. For participants with no PSA decline from baseline, the date of PSA progression is the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from baseline are documented beyond Week 13. TTPPSA will be censored at the date of last PSA evaluation prior to the start of subsequent systemic cancer therapy. The time will be censored at the date of randomization for participants with no post-baseline PSA evaluation. - Overall safety and tolerability will be measured by the incidence of AEs, SAEs, AEs leading to discontinuation, immune-mediated AEs, select AEs, deaths, and laboratory abnormalities and changes from baseline. - Median time to pain progression as assessed by Brief Pain Inventory-Short Form (BPI-SF) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Incidence of AEs, SAEs, deaths and laboratory abnormalities in all treated participants |
Incidenza di eventi avversi, eventi avversi sei, decessi e anomalie di laboratorio in tutti i partecipanti trattati |
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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 | Yes |
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 | 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) | 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) | No |
E.8.2.2 | Placebo | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 89 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
Hong Kong |
Israel |
Japan |
Korea, Democratic People's Republic of |
Mexico |
Russian Federation |
Singapore |
Taiwan |
Turkey |
United States |
Austria |
Belgium |
Czechia |
France |
Germany |
Italy |
Poland |
Romania |
Spain |
United Kingdom |
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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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The last visit or scheduled procedure for the last participant |
L'ultima visita o procedura pianificata per l'ultimo partecipante |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |