E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma that has progressed on or after a trastuzumabcontaining regimen |
adenocarcinoma non resecabile o adenocarcinoma metastatico gastrico o adenocarcinoma della giunzione gastro-esofagea (GGE) che ha manifestato una progressione durante o dopo un regime contenente trastuzumab |
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E.1.1.1 | Medical condition in easily understood language |
HER2-POSITIVE, UNRESECTABLE OR METASTATIC GASTRIC OR GASTROESOPHAGEAL JUNCTION (GEJ) ADENOCARCINOMA |
adenocarcinoma HER2 positivo, non resecabile o metastatico gastrico o della giunzione gastro-esofagea (GGE) |
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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 | LLT |
E.1.2 | Classification code | 10071114 |
E.1.2 | Term | Metastatic gastric adenocarcinoma |
E.1.2 | System Organ Class | 100000004864 |
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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 | 10066354 |
E.1.2 | Term | Adenocarcinoma of the gastroesophageal junction |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To investigate the efficacy of Trastuzumab Deruxtecan (DS-8201a) based on objective response rate (ORR) by independent central review based on Response Evaluation Criteria in Solid Tumors (RECIST), version (v)1.1 |
Studiare l’efficacia di trastuzumab deruxtecan in base al tasso di risposta obiettiva (ORR), attraverso una revisione centrale indipendente sulla base dei Criteri di valutazione della risposta nei tumori solidi (RECIST) versione (v) 1.1 |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of Trastuzumab Deruxtecan on progressionfree survival (PFS), based on independent central review using RECIST v1.1. Other secondary objectives: - To further evaluate the efficacy of Trastuzumab Deruxtecan using the endpoint of overall survival (OS) - To further evaluate the efficacy of Trastuzumab Deruxtecan using RECIST v1.1 for endpoints of PFS and ORR based on Investigator assessment, and on duration of response (DoR) based on independent central review and Investigator assessment - To determine the pharmacokinetics (PK) of Trastuzumab Deruxtecan in serum - To further evaluate the safety of Trastuzumab Deruxtecan based on treatment-emergent adverse events (TEAEs) and anti-drug antibodies (ADAs) - To evaluate Health Economics and Outcomes Research (HEOR) endpoints based on patient-reported outcomes (PROs) |
• Valutare l’efficacia dell'IMP sulla sopravvivenza libera da progressione (PFS), in base a una revisione centrale indipendente usando i criteri RECIST v1.1. Altri obiettivi_ • Valutare ulteriormente l’efficacia dell'IMP utilizzando l’endpoint della sopravvivenza complessiva (OS) • Valutare ulteriormente l’efficacia dell'IMP utilizzando i criteri RECIST v1.1 per gli endpoint di PFS e tasso di risposta obiettiva (ORR) in base alla valutazione dello sperimentatore, e della durata della risposta (DoR) in base alla revisione centrale indipendente e alla valutazione dello sperimentatore • Determinare la farmacocinetica (PK) dell'IMP nel siero • Valutare ulteriormente la sicurezza dell'IMP sulla base di eventi avversi emergenti dal trattamento (TEAE) e anticorpi anti-farmaco (ADA) • Valutare gli endpoint Health Economics and Outcomes Research (HEOR) in base agli esiti riferiti dai pazienti (PRO) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men or women =18 years old (Please follow local regulatory requirements if the legal age of consent for study participation is >18 years old.) - Has pathologically documented gastric or GEJ cancer that is: - Unresectable or metastatic - Centrally confirmed HER2-positive disease (immunohistochemistry [IHC]3+, IHC2+/in-situ hybridization [ISH]+) as determined according to American Society of Clinical Oncology – College of American Pathologists (ASCO-CAP) guidelines based on a new tissue sample obtained after progression on or after a trastuzumabcontaining regimen. If a tissue sample was already collected after discontinuation of first-line treatment with a trastuzumab-containing regimen, it is acceptable to consider this a new biopsy for the purpose of this study. - Experienced disease progression during or after first-line therapy with a trastuzumab-containing regimen (brand or approved biosimilar). Note: Prior adjuvant therapy with a trastuzumab-containing regimen can be counted as a line of therapy if the subject progressed on or within 6 months of completing adjuvant therapy. - Has at least 1 measurable lesion per RECIST v1.1 as confirmed by independent central review. - Has left ventricular ejection fraction (LVEF) =50% within 28 days before enrollment per echocardiogram (ECHO)/multigated acquisition (MUGA) scan. - Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4.5 months after the last dose of study drug. - Adequate renal function, defined as creatinine clearance =30 mL/min, as calculated using the Cockcroft-Gault equation. - Adequate hepatic function, defined as total bilirubin =1.5 × upper limit of normal (ULN); serum albumin =2.8 g/dL; aspartate transaminase (AST)/alanine transaminase (ALT) =3 × ULN in the absence of liver metastases or =5 × ULN in the presence of liver metastases. |
• Uomini o donne di età =18 anni (La preghiamo di seguire i requisiti normativi locali, se la maggiore età di consenso per la partecipazione allo studio è >18 anni.) • Presenta tumore gastrico o GGE documentato dal punto di vista patologico con le seguenti caratteristiche: ¿ Non resecabile o metastatico ¿ Malattia HER2 positiva confermata a livello centrale (immunoistochimica [IHC]3+, ibridazione IHC2+/in-situ [ISH]+) come determinato in base alle linee guida dell’American Society of Clinical Oncology – College of American Pathologists (ASCO-CAP) in base a un nuovo campione di tessuto ottenuto in seguito a progressione durante o dopo un regime contenente trastuzumab. Se, dopo la sospensione del trattamento di prima linea con un regime contenente trastuzumab, è già stato prelevato un campione di tessuto, è accettabile prenderlo in considerazione come nuova biopsia ai fini di questo studio. • Progressione della malattia che si è manifestata durante o dopo la terapia di prima linea con un regime contenente trastuzumab (o biosimilare approvato). Nota: Una precedente terapia adiuvante con un regime contenente trastuzumab può essere considerata come una linea di terapia se il soggetto ha avuto una progressione a, o entro, 6 mesi dal completamento della terapia adiuvante. • Presenta almeno 1 lesione misurabile secondo i criteri RECIST v1.1 come confermato dalla revisione centrale indipendente. • Presenta frazione di eiezione ventricolare sinistra (FEVS) =50% nei 28 giorni precedenti l’arruolamento per ecocardiogramma (ECO)/scansione con acquisizione a gate multipli (MUGA). • I soggetti di sesso maschile e femminile potenzialmente fertili devono accettare di usare un metodo contraccettivo altamente efficace o evitare rapporti sessuali durante e al completamento dello studio per almeno 4,5 mesi dopo l’ultima dose del farmaco dello studio. • Adeguata funzionalità renale, definita come clearance della creatinina =30 ml/min, calcolata utilizzando l’equazione di Cockcroft Gault. • Funzione epatica adeguata, definita come bilirubina totale =1,5 × il limite superiore della norma (ULN); albumina sierica =2,8 g/dl; aspartato transaminasi (AST)/alanina transaminasi (ALT) =3 × l’ULN in assenza di metastasi epatiche o =5 × l’ULN in presenza di metastasi epatiche. |
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E.4 | Principal exclusion criteria |
- Use of anticancer therapy after first-line treatment with a trastuzumabcontaining regimen. - Uncontrolled or significant cardiovascular disease, including any of the following: - History of myocardial infarction (MI) within 6 months before enrollment - History of symptomatic congestive heart failure (New York Heart Association Class II to IV) - Troponin levels consistent with MI as defined according to the manufacturer within 28 days prior to enrollment - History of unstable angina or serious cardiac arrhythmia requiring treatment - Corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (male) based on Screening triplicate 12-lead electrocardiogram (ECG) - History of (non-infectious) interstitial lung disease (ILD) or pneumonitis that required corticosteroid therapy or has current ILD/pneumonitis or is suspected to have such diseases by imaging during Screening. - Clinically significant corneal disease, in the opinion of the Investigator. - Pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to or during Screening.) - Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. - Subjects with clinically inactive brain metastases may be included in the study. - Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy). |
• Uso di terapia antitumorale dopo il trattamento di prima linea con un regime contenente trastuzumab. • Malattia cardiovascolare non controllata o significativa, inclusa una qualsiasi delle seguenti: ¿ Anamnesi di infarto miocardico (IM) nei 6 mesi precedenti l’arruolamento ¿ Anamnesi di insufficienza cardiaca congestizia sintomatica (classe II-IV secondo la New York Heart Association) ¿ Livelli di troponina coerenti con un’eziologia di IM, in base alla definizione del produttore, nei 28 giorni precedenti l’arruolamento ¿ Anamnesi di angina instabile o grave aritmia cardiaca che richieda trattamento ¿ Prolungamento dell’intervallo QT corretto (QTc) >470 ms (soggetti di sesso femminile) o >450 ms (soggetti di sesso maschile) in base a Screening per mezzo di elettrocardiogramma a 12 derivazioni (ECG) in triplicato • Anamnesi di malattia polmonare interstiziale (ILD) o polmonite (non infettiva) che ha richiesto una terapia a base di corticosteroidi, o polmonite/ILD corrente o sospetta in base all’esame diagnostico per immagini durante lo Screening. • Malattia della cornea clinicamente significativa, in base al giudizio dello sperimentatore. • Effusione pleurica, ascite, o effusione pericardica che richiede drenaggio, shunt peritoneale, o Terapia di reinfusione per l’ascite libera circolante e concentrata (Cell-free and Concentrated Ascites Reinfusion Therapy, CART). (Il drenaggio e la CART non sono consentiti nelle 2 settimane precedenti, o durante, lo Screening.) • Compressione del midollo spinale o metastasi a carico del sistema nervoso centrale clinicamente attive, definite come non trattate e sintomatiche o che richiedano terapia con corticosteroidi o anticonvulsivanti per il controllo dei sintomi associati. ¿ I soggetti con metastasi cerebrali clinicamente inattive possono essere inclusi nello studio. ¿ I soggetti con metastasi cerebrali trattate che non sono più sintomatiche e che non richiedono il trattamento con corticosteroidi o anticonvulsivanti possono essere inclusi nello studio se si sono ripresi dagli effetti tossici acuti della radioterapia. Devono essere trascorse almeno 2 settimane tra la fine della radioterapia sull’intero cervello e l’arruolamento nello studio (1 settimana per la radioterapia stereotassica). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed ORR (objective response rate) based on independent central review |
ORR confermato, basato sulla revisione centrale indipendente |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis of ORR will be performed for all enrolled subjects at the 18- week tumor assessment. |
L'analisi dell'ORR verrà eseguita per tutti i soggetti arruolati a 18 settimane dalla valutazione del tumore |
|
E.5.2 | Secondary end point(s) |
Progression-Free Survival (PFS) , based on independent central review using RECIST v1.1.; Other Secondary Endpoints: - PFS, based on Investigator assessment - Objective response rate (ORR), based on Investigator assessment - Overall survival (OS) - Duration of Response (DoR), based on independent central review and Investigator assessment |
PFS, basata sulla revisione centrale indipendente, utilizzando RECIST v1.1; Altri endpoint secondari • PFS, basata sulla valutazione dello sperimentatore • ORR, basato sulla valutazione dello sperimentatore • OS • Durata della risposta, in base alla revisione centrale indipendente e alla valutazione dello sperimentatore |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Along the study. Based on independent central review; Along the study. Based on independent central review |
Durante lo studio, basata sulla revisione di un comitato centrale indipendente; Durante lo studio, basata sulla revisione di un comitato centrale indipendente |
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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 | Yes |
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 | Yes |
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) | 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 | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
United States |
Belgium |
Italy |
Spain |
United Kingdom |
|
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
|
The end of the study will occur when all enrolled subjects have either completed their last scheduled visit or died or withdrawn from study participation, which is anticipated to occur approximately 12 months after the last subject is enrolled |
la fine dello studio si verificherà quando tutti i soggetti arruolati avranno completato l'ultima visita programmata o sono deceduti o ritirati dallo studio, il che si prevede che si verifichi circa 12 mesi dopo l'arruolamento dell'ultimo soggetto |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |