E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MET Amplified Gastric (G), Gastroesophageal Junction (GEJ), or Esophageal (E) Adenocarcinoma or Other MET Amplified Solid Tumors |
Adenocarcinomi solidi MET amplificati gastric (G), della giunzione gastroesofagea (GEJ) o esofagei (E) o altri tumori solidi MET amplificati |
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E.1.1.1 | Medical condition in easily understood language |
Esophageal, Gastroesophageal Junction and Gastric Cancer |
Cancro dello stomaco, dell’esofago e della giunzione gastrica-esogafo |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030137 |
E.1.2 | Term | Oesophageal adenocarcinoma |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine antitumor activity of AMG 337 in subjects with MET amplified G/GEJ/E adenocarcinoma. |
Determinazione dell’attività antitumorale di AMG 337 nei soggetti affetti da adenocarcinoma G/E/GEJ amplificato da MET |
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E.2.2 | Secondary objectives of the trial |
To determine the antitumor activity of AMG 337 in subjects with other MET amplified solid tumors. Evaluate the safety and pharmacokinetics (PK) of AMG 337. |
Determinazione dell’attività antitumorale di AMG 337 nei soggetti affetti da altri tumori solidi amplificati da MET. Valutazione della sicurezza e della farmacocinetica di AMG 337 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
General
- Subjects have provided informed consent/assent prior to initiation of any study-specific activities/procedures or subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of
the investigator, may compromise the ability of the subject to give written informed consent.
- Subjects have agreed to and are able to daily self-administer AMG 337 orally as a whole capsule
Demographic
- Male or female subjects ≥ 18 years of age at the time of enrollment
Disease-related
- Subjects must have a pathologically confirmed advanced G/GEJ/E
adenocarcinoma (Cohort 1) or other solid tumor (Cohort 2) for which the subject has received prior therapy for advanced disease, or for which no standard therapy exists, or the subject refuses standard therapy
- Tumor MET amplified by protocol-specified centralized testing. Testing may be performed by central laboratory prior to main study informed consent if subject signs a separate consent for the purposes of tumor tissue testing
- Availability of recent (preferred) or archival tumor tissue
- Measurable disease per RECIST 1.1 guidelines. Cohort 2 may include up to 10 subjects with advanced MET amplified, G/GEJ/E adenocarcinoma with non-measurable tumor per RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Laboratory
- Adequate organ function as evidenced by the following laboratory studies within 28 days prior to enrollment:
● Hemoglobin ≥ 9 g/dL
● Absolute neutrophil count ≥ 1.5 x 109/L
● Platelet conut ≥ 100 x 109/L
● Creatinine clearanc≥e 50 mL/minute (calculated or measured)
● Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) or AST and ALT ≤ 5.0 x ULN if liver metastases are present
● Total bilirubin (TBL) ≤ 1.5 x ULN
● International normalized ratio (INR) ≤ ULN |
Consegna del consenso informato prima dell’inizio di qualsiasi procedura/attività inerente allo studio.
Soggetti che hanno acconsentito e sono in grado di assumere in modo autonomo ogni giorno AMG 337 per via orale in capsule intere.
Demografici:
Soggetti di sesso maschile o femminile di età 18 anni.
Soggetti affetti da adenocarcinoma G/E/GEJ (Coorte 1) o altri tumori solidi (Coorte 2) patologicamente confermati che hanno ricevuto in precedenza una terapia per il trattamento della patologia in stadio avanzato o per cui non esiste un trattamento standard o che si rifiutano di seguire la terapia standard.
Tumori amplificati da MET secondo l’analisi centralizzata indicata dal protocollo.
Disponibilità di un tessuto tumorale archiviato di recente (preferibile).
Patologia misurabile secondo le linee guida RECIST 1.1. La Coorte 2 includerà fino a 10 soggetti affetti da adenocarcinoma G/E/GJE amplificato da MET con tumore non misurabile mediante RECIST 1.1.
Performance status ECOG (Eastern Cooperative Oncology Group) pari a 0 o 1.
Laboratorio:Un’adeguata funzione d’organo documentata dai seguenti studi di laboratorio nei 28 giorni precedenti l’arruolamento.
- Emoglobina ≥9 g/dL
- Conta assoluta dei neutrofili ≥1,5 x 109/L
- Conta piastrinica ≥100 x 109/L
- Clearance della creatinina ≥50 mL/minuto (calcolata o misurata)
- Aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT) ≤2,5 x limite superiore di normalità (ULN) o AST e ALT ≤5,0 x ULN, in presenza di metastasi del fegato.
- Bilirubina totale ≤1,5 x ULN
- Rapporto internazionale normalizzato (INR) ≤ ULN
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E.4 | Principal exclusion criteria |
- Known central nervous system metastases. Subject is a candidate for curative surgery or definitive chemoradiation. Peripheral edema > grade 1.
Currently receiving any anti-tumor treatments, or less than 14 days prior to enrollment since ending anti-tumor treatment.
- Therapeutic or palliative radiation therapy less than 14 days prior to study day 1 or still experiencing toxicities from radiation therapy or radiation therapy administered to the only site of
disease.
- Use of a strong CYP3A4 inhibitor less than 14 days prior to study day 1.
- Ingestion of grapefruit or grapefruit products and other foods that are known to inhibit CYP3A4 less than 7 days prior to study day 1.
- Use of strong CYP3A4 inducers less than 14 days prior to study day 1.
- Use of St. John’s Wort and other herbal supplements known to induce CYP3A4 less than 14 days prior to study day 1. |
Metastasi note del sistema nervoso centrale. Il soggetto è in attesa di un intervento di chirurgia curativa o chemio-radioterapia definitiva. Edema periferico di grado superiore a 1. - Soggetto attualmente in trattamento con un agente antitumorale o che ha concluso la terapia antitumorale da meno di 14 giorni prima dell’arruolamento.
- Radioterapia terapeutica o palliativa nei 14 giorni precedenti il Giorno 1 dello studio o tossicità legate alla radioterapia ancora in corso o radioterapia somministrata esclusivamente a livello della sede della patologia.
- Uso di un forte inibitore del CYP3A4 da meno di 14 giorni prima del Giorno 1 dello studio.
- Assunzione di succo di pompelmo o di prodotti contenenti questa bevanda o altri cibi che notoriamente inibiscono il CYP3A4 nei 7 giorni precedenti il Giorno 1 dello studio.
- Uso di forti induttori del CYP3A4 da meno di 14 giorni prima del Giorno 1 dello studio. - - Assunzione dell’erba si St. John o altri integratori /prodotti naturali che inducono il CYP3A4 nei 14 giorni precedenti il Giorno 1 dello studio.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR, per RECIST v1.1) in subjects with MET amplified measurable G/GEJ/E adenocarcinoma (Cohort 1) |
ORR (Objective response rate - secondo RECIST 1.1) nei soggetti affetti da adenocarcinoma G/E/GEJ misurabile amplificato da MET (Coorte 1). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumour assessment scans will be taken at screening, week 8 (± 3 days), and then every 8 weeks (Q8W) (± 7 days) during study treatment until week 32, independent of treatment cycle. From week 32 onward, tumour assessment scans will be taken every 12
weeks (Q12W) (± 7 days) during study treatment, independent of treatment cycle. |
La valutazione tumorale sarà fatta allo screening, settimana 8 (+- 3 gg) e quindi ogni 8 settimane (Q8W) 8+-7 gg) durante la fase di trattamento fino alla settimana 32, indipendentemente dal ciclo di trattamento . A partire dalla settimana 32 la valutazione tumorale sarà effettuata ogni 12 settimane (Q12W) 8+-7 gg) durante la fase di trattamento, indipendentemente dal ciclo di trattamento. |
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E.5.2 | Secondary end point(s) |
- ORR (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in Cohort 2)
- DOR (duration of response) (Cohort 1 and subjects with measurable disease at baseline in Cohort 2)
- Time to response (TTR) (Cohort 1 and subjects with measurable disease at baseline in Cohort 2)
- Progression-free survival (PFS)
- Overall survival (OS)
- Incidence and severity of adverse events and significant laboratory abnormalities
- AMG 337 exposure and dose intensity
- Pharmacokinetic parameters including, but not limited to, minimum (trough) concentrations at pre-dose times, maximum concentration (Cmax), the time of Cmax (tmax), and area under the plasma concentration – time curve (AUC) |
• ORR (secondo RECIST 1.1) nei soggetti affetti da altri tumori solidi amplificati da MET (soggetti con patologia misurabile della Coorte 2).
• Durata della risposta (Duration Of Response, DOR) (Coorte 1 e soggetti con patologia misurabile al basale della Coorte 2).
• Tempo alla risposta (Time To Response, TTR) (Coorte 1 e soggetti con patologia misurabile al basale della Coorte 2).
• Sopravvivenza libera da progressione (Progression-Free Survival, PFS).
• Sopravvivenza globale (OS).
• Incidenza e gravità di eventi avversi e anomalie di laboratorio significative.
• Intensità della dose ed esposizione a AMG 337.
• Parametri farmacocinetici quali, a titolo esemplificativo ma non esaustivo, concentrazioni (basali) minime pre-dose, concentrazione massima (Cmax), tempo per raggiungere la Cmax (tmax) e area sotto la curva di concentrazione plasmatica in funzione del tempo (AUC).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumour assessment scans will be taken at screening, week 8 (± 3 days), and then every 8 weeks (Q8W) (± 7 days) during study treatment until week 32, independent of treatment cycle. From week 32 onward, tumour assessment scans will be taken every 12
weeks (Q12W) (± 7 days) during study treatment, independent of treatment cycle.
Patient-reported outcomes assessment will be done at baseline and at every radiological assessment thereafter, including radiological assessments to confirm tumour progression when symptoms of disease progression occur. CTC and circulating serum biomarkers will also be assessed at baseline and during study treatment. |
La valutazione tumorale sarà fatta allo screening, settimana 8 (+- 3 gg) e quindi ogni 8 settimane (Q8W) 8+-7 gg) durante la fase di trattamento fino alla settimana 32, indipendentemente dal ciclo di trattamento . A partire dalla settimana 32 la valutazione tumorale sarà effettuata ogni 12 settimane (Q12W) 8+-7 gg) durante la fase di trattamento, indipendentemente dal ciclo di trattamento.
La valutazione dei “Patient-reported out come” sarà fatta al basale e quindi ad ogni valutazione radiologica, incluse quelle per confermare la progressione tumorale quando si verificano i sintomi della progressione della malattia. CTC e biomarker circolanti serici verranno inoltre valutati al basale e durante la fase di trattamento.
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Health-related quality of life |
Qualità della vita correlata allo stato di salute |
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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) | 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 | 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 | 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 | Information not present in EudraCT |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
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 | No |
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 |
Belgium |
Canada |
France |
Germany |
Greece |
Hungary |
Italy |
Austria |
Poland |
Russian Federation |
Czech Republic |
Korea, Republic of |
Spain |
United Kingdom |
United States |
Chile |
Peru |
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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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Primary Completion: the time when the last subject is assessed or receives an intervention for the purposes of final collection of data for the final analysis.
End of Trial: the time when the last subject is assessed or receives an intervention for evaluation in the study. |
Completamento primaria: il momento in cui l'ultimo soggetto è valutato o riceve un intervento ai fini della raccolta finale dei dati per l'analisi finale.
Fine della prova: il momento in cui l'ultimo soggetto è valutato o riceve un intervento di valutazione nello studio. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 2 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 2 |