E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Hormone-sensitive Prostate Cancer (mHSPC) |
Carcinoma della prostata metastatico ormono-sensibile (mHSPC). |
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E.1.1.1 | Medical condition in easily understood language |
Prostate Cancer |
Tumore della 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 | 21.1 |
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 determine if the addition of Apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for subjects with mHSPC. |
L'obiettivo primario consiste nel determinare se associando Apalutamide con la ADT la sopravvivenza senza progressione radiografica (rPFS) o la sopravvivenza generale (OS) in soggetti affetti da carcinoma della prostata metastatico ormono-sensibile (mHSPC) migliora significativamente |
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E.2.2 | Secondary objectives of the trial |
To evaluate clinically relevant improvements with addition of Apalutamide to ADT including delays in pain progression and opioid use for prostate cancer, skeletal-related events, and the need for cytotoxic chemotherapy To characterize the safety of adding Apalutamide to ADT in subjects with mHSPC To characterize the population pharmacokinetics (PK) and pharmacodynamics (PD) of Apalutamide To evaluate the concentration of leuprolide and assess the PD effect of leuprolide on testosterone concentrations when used alone or in combination with Apalutamide * To evaluate the treatment effectiveness with the addition of Apalutamide to ADT for the subpopulations of subjects with mHSPC |
-Valutazione dei principali miglioramenti clinici legati all'associazione di Apalutamide alla terapia ADT, inclusi eventuali ritardi nella progressione del dolore e nell¿utilizzo di oppiacei per il cancro alla prostata, eventi legati allo scheletro e la necessit¿ di effettuare chemioterapia citotossica. ¿ Valutazione della sicurezza legata all'aggiunta di Apalutamide alla terapia ADT in pazienti con mHSPC. ¿ Valutazione della farmacocinetica (PK) e farmacodinamica (PD) di Apalutamide. ¿ Valutazione della concentrazione di leuprolide nonch¿ l'effetto farmacodinamico (PD) del leuprolide sulle concentrazioni di testosterone utilizzato da solo o in combinazione con Apalutamide. - Valutare l'efficacia del trattamento con l'aggiunta dell'Apalutamide all'ADT nelle sottopopolazioni di soggetti con mHSPC |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of prostate adenocarcinoma as confirmed by the investigator - Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI) - Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1 - Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization - Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (<=) 6 months of ADT prior to randomization - Allowed prior treatments for localized prostate cancer (all treatments must have been completed >= 1 year prior to randomization) a) <= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy, lymph node dissection and systemic therapies |
- La diagnosi di adenocarcinoma alla prostata deve essere confermata dallo sperimentatore. - Malattia metastatica documentata da =1 lesione ossea con scintigrafia ossea al Tecnezio 99m (99mTc). I soggetti con una lesione ossea devono avere la conferma di tale lesione alla TAC oppure RMN. - Grado di PS ECOG di 0 e 1. - I soggetti trattati in precedenza con docetaxel devono rispettare i seguenti criteri: a) Aver assunto al massimo 6 cicli di docetaxel per l’mHSPC; b) Aver assunto l’ultima dose di docetaxel 2 mesi prima della randomizzazione; c) Avere una risposta almeno stabile al docetaxel, sulla base delle immagini valutate dallo sperimentatore e ai livelli di PSA, prima della randomizzazione. - Terapie pregresse per l’mHSPC: a) Massimo un ciclo di radioterapia oppure intervento chirurgico; la radioterapia palliativa per le metastasi deve essere completata prima della randomizzazione; b) < 6 mesi di ADT prima della randomizzazione. - Trattamenti permessi per il cancro alla prostata localizzato, completati un anno prima dalla randomizzazione: a) < 3 mesi di ADT; b) Tutte le tipologie di terapie comprese la radioterapia, la prostatectomia, la dissezione dei linfonodi e le terapie sistemiche. |
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E.4 | Principal exclusion criteria |
- Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate - Known brain metastases - Lymph nodes as only sites of metastases - Visceral (ie, liver or lung) metastases as only sites of metastases - Other prior malignancy within 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer - Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer - History of seizures or medications known to lower seizure threshold |
- Referti patologici coerenti con il carcinoma della prostata a piccole cellule, duttali o neuroendocrine - Metastasi cerebrali note - Metastasi solo ai linfonodi. -Metastasi viscerali (es. polmone e fegato) come unico sito di metastasi -Altre neoplasie maligne precedenti entro 5 anni dalla randomizzazione ad eccezione di carcinoma della pelle a cellule squamose o carcinoma superficiale alla vescica non invasivo. -Precedente trattamento con altri anti-androgeni di successive generazioni. o altri inibitori CYP17, immunoterapia o agenti radiofarmaceutici per la cura del cancro alla prostata. -Anamnesi di crisi epilettiche o farmaci conosciuti per abbassare la soglia di attacco.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Radiographic Progression-Free Survival (rPFS) - Overall Survival (OS) |
- Sopravvivenza senza progressione radiografica - Sopravvivenza generale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Up to 54 Months - Up to 54 Months |
- Fino a 54 mesi - Fino a 54 mesi |
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E.5.2 | Secondary end point(s) |
- Time to Pain Progression - Time to Skeletal-Related Event (SRE) - Time to Chronic Opioid Use - Time to Initiation of Cytotoxic Chemotherapy |
- Tempo alla progressione del dolore - Tempo prima dell'evento legato allo scheletro (SRE) - Tempo all'utilizzo cronico di oppiodi - Tempo di inizio della chemioterapia con citotossico |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Up to 54 Months - Up to 54 Months - Up to 54 Months - Up to 54 Months |
- Fino a 54 mesi - Fino a 54 mesi - Fino a 54 mesi - Fino a 54 mesi |
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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 | Yes |
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 |
Biomarkers and tumour response assessments |
Biomarker e valutazioni di risposta del tumore |
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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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
Brazil |
China |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Turkey |
Ukraine |
United States |
France |
Germany |
Hungary |
Italy |
Poland |
Romania |
Spain |
Sweden |
Czechia |
Argentina |
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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 fine trattamento: entro 30 giorni dopo l'ultima somministrazione del farmaco in 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 | 6 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |