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 |
adenocarcinoma esofágico (E), de unión gastroesofágica (UGE) o gástrico (G) con amplificación del MET u otros tumores sólidos con amplificación del MET. |
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E.1.1.1 | Medical condition in easily understood language |
Esophageal, Gastroesophageal Junction and Gastric Cancer |
cáncer esofágico, de unión gastroesofágica y gástrico |
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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 | 16.1 |
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 | 16.1 |
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 | 16.1 |
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. |
determinar la actividad antitumoral de AMG 337 en sujetos con adenocarcinoma E/UGE/G con amplificación del 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. |
determinar la actividad antitumoral de AMG 337 en sujetos con otros tumores sólidos con amplificación del MET. Evaluar la seguridad y la farmacocinética (PK) de 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 subjects 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 clearance >= 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 |
Generales - Los sujetos han proporcionado el consentimiento informado/aceptación antes del inicio de cualquier actividad/procedimiento específico del estudio o su representante legal autorizado ha proporcionado el consentimiento informado antes del inicio de cualquier actividad/procedimiento específicos del estudio cuando el sujeto sufre cualquier tipo de enfermedad que, según la opinión del investigador, puede comprometer su capacidad para proporcionar el consentimiento informado. -Los sujetos han aceptado y pueden autoadministrarse diariamente por vía oral AMG 337 en forma de cápsulas enteras.
Demográficos - Sujetos masculinos o femeninos >= 18 años en el momento de la inclusión.
Relacionados con la enfermedad - Los sujetos deben presentar un adenocarcinoma E/UGE/G avanzado y confirmado patológicamente (cohorte 1) u otro tumor sólido (cohorte 2) para el que el sujeto haya recibido un tratamiento previo por enfermedad avanzada, para el que no exista un tratamiento estándar o para el que el sujeto haya rechazado el tratamiento estándar. - Tumor con amplificación del MET según la prueba centralizada especificada en el protocolo. El laboratorio central puede realizar pruebas antes del consentimiento informado del estudio principal si el sujeto firma un consentimiento específico para poder realizar pruebas con el tejido tumoral. - Disponibilidad de tejido tumoral reciente (preferido) o archivado. - Enfermedad medible según los criterios RECIST v.1.1. La cohorte 2 puede incluir hasta 10 sujetos con adenocarcinoma E/UGE/G avanzado con amplificación del MET y tumor no medible según los criterios RECIST v.1.1. - Estado funcional ECOG (Eastern Cooperative Oncology Group) de 0 o 1.
Analíticos - Función orgánica adecuada según los datos de las siguientes pruebas analíticas en los 28 días previos a la inclusión: - Hemoglobina >= 9 g/dL. - Recuento absoluto de neutrófilos >= 1,5 x 109/L. - Recuento de plaquetas >= 100 x 109/L. - Aclaramiento de la creatinina >= 50 mL/minuto (calculado o medido). - Aspartato aminotransferasa (AST) y alanina aminotransferasa (ALT) <= 2,5 x límite superior de la normalidad (LSN), o AST y ALT <= 5,0 x LSN si hay metástasis hepáticas. - Bilirrubina total (BiT) <= 1,5 x LSN. - Cociente normalizado internacional (INR) <= LSN. |
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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. Johns Wort and other herbal supplements known to induce CYP3A4 less than 14 days prior to study day 1. |
- Metástasis en el sistema nervioso central conocidas. - El sujeto es un candidato a recibir cirugía curativa o quimiorradioterapia definitiva. - Edema periférico de grado > 1. - Los sujetos actualmente reciben tratamientos antitumorales o en el momento de la inclusión hace menos de 14 días que han finalizado un tratamiento antitumoral. - El sujeto ha recibido radioterapia terapéutica o paliativa menos de 14 días antes del día 1 del estudio, aún presenta toxicidades relacionadas con la radioterapia o se le ha administrado la radioterapia solo en la localización de la enfermedad. - El uso de un inhibidor potente de la CYP3A4 menos de 14 días antes del día 1 del estudio. - La ingesta de pomelo o productos derivados del pomelo y otros alimentos que se sabe que inhiben la CYP3A4 menos de 7 días antes del día 1 del estudio. - El uso de inductores potentes de la CYP3A4 menos de 14 antes del día 1 del estudio. - El uso de hierba de San Juan y otros suplementos herbales que se sabe inducen la CYP3A4 menos de 14 días antes del día 1 del estudio. |
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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) |
TRO (según RECIST v.1.1) en sujetos con adenocarcinoma E/UGE/G con amplificación del MET (cohorte 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. |
Exploraciones de evaluación tumoral en la semana 8 (± 3 días) y, a partir de entonces, Q8W (± 7 días) hasta la semana 32, independientemente del ciclo de tratamiento. A partir de la semana 32, las exploraciones de evaluación tumoral se realizarán Q12W (± 7 días) durante el tratamiento del estudio, independientemente del ciclo de tratamiento. |
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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) |
TRO (según RECIST v.1.1) en sujetos con otros tumores sólidos con amplificación del MET (sujetos de la cohorte 2 con enfermedad medible). - DR (cohorte 1 y sujetos de la cohorte 2 con enfermedad medible en la situación basal). - Tiempo hasta la respuesta (THR) (cohorte 1 y sujetos de la cohorte 2 con enfermedad medible en la situación basal). - SLP - SG - Incidencia y gravedad de los acontecimientos adversos y anomalías analíticas significativas. - Exposición e intensidad de la dosis de AMG 337. - Parámetros farmacocinéticos incluyendo, entre otros, las concentraciones mínimas (valle) en los momentos anteriores a la dosis, la concentración máxima (Cmáx), el tiempo hasta la Cmáx (tmáx) y el área bajo la curva de la concentración plasmática en función del tiempo (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. |
Exploraciones de evaluación tumoral en la semana 8 (± 3 días) y, a partir de entonces, Q8W (± 7 días) hasta la semana 32, independientemente del ciclo de tratamiento. A partir de la semana 32, las exploraciones de evaluación tumoral se realizarán Q12W (± 7 días) durante el tratamiento del estudio, independientemente del ciclo de tratamiento. Se debe completar un cuestionario PRO al inicio del estudio y en cada evaluación radiológica no programada llevada a cabo como resultado de una progresión de la enfermedad sintomática. También se evaluarán muestras para CTC, suero y plasma para pruebas de biomarcadores en el início y durante el tratamiento del estudio. |
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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 |
Calidad de vida relacionada con la salud |
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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 | No |
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 | 7 |
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 |
Belgium |
Canada |
France |
Greece |
Italy |
Austria |
Australia |
Chile |
Czech Republic |
Germany |
Hungary |
Korea, Republic of |
Spain |
Peru |
Poland |
Russian Federation |
United Kingdom |
United States |
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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. |
Finalización principal: se define como el momento en que el último sujeto se evalúa o recibe una intervención con la intención de recopilar los últimos datos para el análisis final.
Fin del ensayo: el momento en que el último sujeto se evalúa o recibe una intervención para la evaluación en el estudio. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 30 |
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 |