E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human epidermal growth factor receptor 2 (HER2)- expressing advanced colorectal cancer |
Cancro al colon-retto in fase avanzata che esprime HER2. |
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E.1.1.1 | Medical condition in easily understood language |
Human epidermal growth factor receptor 2 (HER2)- expressing advanced colorectal cancer |
Cancro al colon-retto in fase avanzata che esprime HER2. |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010029 |
E.1.2 | Term | Colorectal cancer NOS |
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 determine the objective response rate (ORR) of DS-8201a in HER2-expressing advanced metastatic colorectal cancer patients |
Determinare il tasso di risposta obiettiva (Objective Response Rate, ORR) di DS-8201a nei pazienti affetti da carcinoma del colon-retto in stadio avanzato, metastatico con espressione di HER2. |
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E.2.2 | Secondary objectives of the trial |
¿To evaluate duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). ORR assessed by the investigator is also evaluated. ¿To evaluate the safety of DS-8201a ¿To determine the pharmacokinetics (PK) of DS-8201a |
¿ Stimare la durata della risposta (Duration of Response, DoR), il tasso di controllo della malattia (Disease Control Rate, DCR), la sopravvivenza senza progressione (Progression-Free Survival, PFS) e la sopravvivenza globale (Overall Survival, OS). Sar¿ inoltre valutata l¿ORR stimata dallo sperimentatore. ¿ Valutare la sicurezza di DS-8201a ¿ Determinare l¿analisi farmacocinetica (PK) di DS-8201a
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Pathologically documented unresectable, recurrent, or metastatic colorectal adenocarcinoma. Until sponsor's notification to the study sites, subject must be a (BRAF) wild-type cancer. 2. Received at least 2 prior regimens of standard treatment. 3. Has measurable disease assessed by the investigator based on RECIST version 1.1. 4. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 |
1. Adenocarcinoma del colon-retto non resecabile, recidivante o metastatico, documentato dal punto di vista patologico. Fino alla notifica dello sponsor ai centri dello studio, il soggetto deve presentare un tumore ”wild-type” per BRAF. 2. Trattamento con almeno 2 regimi di trattamento standard in precedenza. 3. Ha una malattia misurabile verificata dallo sperimentatore sulla base dei RECIST V 1.1 4. Ha un ECOG PS da 0 a 1
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E.4 | Principal exclusion criteria |
1. Medical history of myocardial infarction within 6 months before enrollment (study treatment), symptomatic congestive heart failure 2 Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening 3. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy |
1. Anamnesi di infarto miocardico nei 6 mesi precedenti l'arruolamento (trattamento dello studio), insufficienza cardiaca congestizia sintomatica 2. Ha avuto ILD/polmonite (non infettiva) che ha richiesto il trattamento con steroidi, soffre attualmente di ILD/polmonite o si sospetta tale malattia sulla base degli esami per immagini durante il periodo di screening 3. Compressione del midollo spinale o metastasi clinicamente attive al sistema nervosa central, definite come non trattate e sintomatiche, o che richiedono terapie
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) per imaging assessment - Percentage of participants with objective response per independent central imaging facility review based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 |
Tasso di risposta oggettivo (ORR) basato sui test per immagini - Percentuale di partecipanti con risposta oggettiva basata sui dati del laboratorio centralizzato per le immagini (criteri per la valutazione della risposta in t umori solidi - RECIST) versione 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 6 wekks |
Ogni 6 settimane |
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E.5.2 | Secondary end point(s) |
¿Progression-free survival ¿Overall survival ¿Duration of response ¿Disease control rate (DCR) ¿ORR assessed by the investigator based on RECIST version 1.1 The following apply to categories; DS-8201a, total anti-HER2 antibody, and MAAA-1181a ¿Maximum serum/plasma concentration (Cmax) ¿ Time to Cmax (Tmax) ¿Area under the concentration-time curve (AUC) ¿AUC from the time of dosing until day 21 (AUC0-21d) |
¿Sopravvivenza libera da progression ¿Sopravvivenza complessiva ¿Durata della risposta ¿Tasso di controllo della malattia (DCR) ¿ORR valutata dallo sperimentatore sulla base dei RECIST versione 1.1
I seguenti si applicano alle categorie; DS-8201a, anticorpo anti-HER2 totale e MAAA-1181a ¿Massima concentrazione plasma/siero (Cmax) ¿ Tempo per raggiungere la Cmax (Tmax) ¿Area sotto la curva (AUC) ¿AUC dal momento della somministrazione fino al giorno 21 (AUC0-21d) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 6 weeks for efficacy, OS for until death or last contact with subject |
Ogni 6 settimane per efficacia, OSfino alla morte o all'ultimo contatto con il paziente |
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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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Lo studio non è controllato, ma il sistema impedisce di andare oltre se non si clicca "Sì" al punto |
The trial is not controlled, but the system impedes you to go further if point E.8.1 is "No" |
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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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Japan |
United States |
Italy |
Spain |
United Kingdom |
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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
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End of OS follow-up |
Fine del follow-up per OS. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |