E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
FGFR, Amplification, polysomy, gastro-oesophageal junction cancer, gastric cancer, randomised, efficacy |
FGFR, amplificación, polisomía, cáncer de la unión gastroesofágica, cáncer gástrico, aleatorización, eficacia |
|
E.1.1.1 | Medical condition in easily understood language |
stomach and food-pipe cancer, anti-tumour activity, high number of copies of gene driving cancer |
cáncer de estómago y esófago, actividad anti-tumoral, número alto de copias de genes que producen cáncer |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030159 |
E.1.2 | Term | Oesophageal carcinoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061967 |
E.1.2 | Term | Gastric cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063916 |
E.1.2 | Term | Metastatic gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030155 |
E.1.2 | Term | Oesophageal carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017761 |
E.1.2 | Term | Gastric cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017765 |
E.1.2 | Term | Gastric cancer stage III |
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 |
To assess the relative efficacy of AZD4547 compared with paclitaxel by comparison of the change in tumour size at 8 weeks in all randomised patients and also in the patients with tumours that have FGFR2 amplification (FISH score 6) alone. |
Valorar la eficacia relativa de AZD4547 en comparación con paclitaxel mediante comparación del cambio del tamaño tumoral a las 8 semanas en todos los pacientes aleatorizados y también exclusivamente en los pacientes con tumores que tienen amplificación de FGFR2 (puntuación de FISH 6). |
|
E.2.2 | Secondary objectives of the trial |
To assess the relative efficacy of AZD4547 compared with paclitaxel by assessment of progression-free survival (PFS) in all randomised patients and also in the patients with tumours that have FGFR2 amplification (FISH score 6) alone. To investigate the efficacy of AZD4547 compared with paclitaxel by assessment of objective response rate (ORR) in all randomised patients and also in the patients with tumours that have FGFR2 amplification (FISH score 6) alone To assess the efficacy of AZD4547 and paclitaxel by assessment of the percentage of patients without progressive disease at 8 weeks. To compare and assess the safety and tolerability of AZD4547 and paclitaxel. To investigate the PK of AZD4547 in an advanced gastric cancer patient population. To investigate the possible pharmacokinetic/pharmacodynamic (PK/PD) relationships between plasma AZD4547 exposure and plasma concentrations of phosphate, bFGF, FGF23 and efficacy and other exploratory PD endpoints. |
Evaluar eficacia relativa de AZD4547 en comparación con paclitaxel mediante la evaluación de la supervivencia libre de progresión (SLP) en los pacs aleatorizados y tb. exclusivamente en los pacs. con tumores que tienen amplificación de FGFR2 (FISH 6). Investigar la eficacia de AZD4547 en comparación con paclitaxel mediante evaluación de la tasa de respuestas objetivas (TRO) en los pacs. aleatorizados y tb. exclusivamente en los pacs, con tumores que tienen amplificación de FGFR2 (FISH 6). Evaluar la eficacia de AZD4547 y paclitaxel mediante la evaluación del % de pacs. sin progresión de la enfermedad a las 8 semanas. Comparar y evaluar la seguridad y la tolerabilidad de AZD4547 y paclitaxel. Investigar la FC de AZD4547 en una población de pacs. con cáncer gástrico avanzado. Investigar las posibles relaciones FC/FD entre la exposición a AZD4547 en el plasma y las concentraciones plasmáticas de fosfato, bFGF, FGF23 y la eficacia y otros criterios de valoración FD exploratorios. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Genetic sub-study: see protocol and ICF for genetic investigation Objectives: to explore how genetic variations may affect the clinical parameters associated with AZD4547. Collection of DNA samples from populations with well-described clinical characteristics may lead to improvements in the design and interpretation of clinical studies and possibly to genetically guided treatment strategies. |
Sub-study genético: ver protocolo y HIP y CI para investigación genética Objetivos: Explorar el modo en que las variaciones genéticas pueden afectar a los parámetros clínicos asociados a AZD4547. La recogida de muestras de ADN de poblaciones con características clínicas bien descritas puede conducir a la mejora en el diseño y la interpretación de los ensayos clínicos y posiblemente a estrategias de tratamiento orientadas genéticamente. |
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E.3 | Principal inclusion criteria |
Female or male aged 25 or over Histological diagnosis of locally advanced or metastatic gastro adenocarcinoma (including adenocarcinoma of the lower third of the oesophagus or the gastro oesophageal junction ) Radiographically confirmed progression after 1 prior chemotherapy or chemoradiotherapy for gastric cancer. Suitable for and expected to benefit from paclitaxel monotherapy. At least one lesion, not previously irradiated, that at baseline is equal to or larger than 10mm in the longest diameter for non nodal lesions with CT or MRI Provision of either an archival tumour sample or a fresh tumour sample for confirmation of FGFR2 polysomy/gene amplification by the sponsor approved laboratory. Patients with FGFR2 polysomy or gene amplified tumours will be eligible for the main study |
Mujer o varón de 25 años o más. Diagnóstico histológico de adenocarcinoma gástrico localmente avanzado o metastásico (incluido el adenocarcinoma del tercio inferior del esófago o de la unión gastroesofágica). Progresión confirmada radiológicamente después de una quimioterapia o quimiorradioterapia previa para el cáncer gástrico. Pacientes idóneos y que se espere que puedan obtener beneficio con el tratamiento con paclitaxel Al menos una lesión, no irradiada previamente, que en el momento basal sea >/= 10 mm en el diámetro más largo para lesiones no nodulares con TC o RM Provisión de una muestra tumoral de archivo o nueva para la confirmación de polisomía o amplificación génica de FGFR2 por un laboratorio autorizado por el promotor. Los pacientes con tumores con polisomía o amplificación génica de FGFR2 serán elegibles para el estudio principal |
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E.4 | Principal exclusion criteria |
Prior exposure to AZD4547 or history of hypersensitivity other drugs similar in structure or class to AZD4547. Hypersensitivity to paclitaxel or formulated in Cremaphor EL (polyoxyethylated castor oil) Major surgery, radiotherapy with wide field of radiation or any cancer treatment within 4 weeks before the first dose of the study treatment With the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for AE (CTCAE) grade >1 at the time of starting study treatment. Blood and ECG readings that are deemed to be abnormal by falling outside of the reference ranges in the protocol inclusion/exclusion section. Taking other regular medication that are predicted to interact with AZD4547 due to their route of metabolism. |
Exposición previa a AZD4547 o antecedente de hipersensibilidad a otros fármacos similares en estructura o clase a AZD4547. Hipersensibilidad a paclitaxel o u otros fármacos formulados en Cremaphor EL (aceite de ricino polioxietilado) Cirugía mayor, radioterapia con un campo amplio de irradiación o cualquier tratamiento para el cáncer en el plazo de 4 semanas antes de la primera dosis del tratamiento en estudio. A excepción de la alopecia, cualquier toxicidad no resuelta de tratamiento previo con un grado > 1 de los Criterios de Terminología Común para Acontecimientos Adversos (CTCAE) en el momento de comenzar el tratamiento del ensayo Lecturas de sangre y ECG que se consideren anormales por no entrar en el ámbito de los rangos de referencia incluidos en el apartado de criterios de inclusión/exclusión del protocolo. Toma regular de medicación que se prevé interactúe con AZD4547 debido a su ruta metabólica. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of relative efficacy of AZD4547 compared with paclitaxel by comparison of the change in tumour size at 8 weeks in all patients and also in patients with FGFR2 amplified tumours (FISH 6) alone |
Evaluar la eficacia relativa de AZD4547 en comparación con paclitaxel comparando el cambio en el tamaño del tumor a las 8 semanas en todos los pacientes y también exclusivamente en los pacientes con tumores que tienen amplificación de FGFR2 (puntuación FISH de 6). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Based on RECIST measurements taken at baseline and at week 8. |
Basados en las determinaciones RECIST tomadas al inicio y al a semana 8 |
|
E.5.2 | Secondary end point(s) |
Relative efficacy of AZD4547 compared with paclitaxel by assessment of progression free survival (defined by RECIST 1.1 or death), in all randomized patients and also in patients with FGFR2 amplified tumours (FISH 6) alone Efficacy of AZD4547 compared with paclitaxel by assessment of objective response rate (1 visit response of CR or PR prior to progression as defined by RECIST 1.1) in randomized patients and also in patients with FGFR2 amplified tumours (FISH 6) alone Assess the efficacy of AZD4547 and paclitaxel by assessment of the percentage of patients without progressive disease at 8 weeks Safety and tolerability of AZD4547 versus paclitaxel by assessing safety information (lab findings, ECG, adverse events, deaths, physical examination, eye asssessments and MUGA/Echo parameters) Investigate PK of AZD4547 in advanced gastric cancer patient population. |
Evaluar la eficacia relativa de AZD4547 en comparación con paclitaxel mediante la evaluación de la supervivencia libre de progresión (definida como RECIST 1.1 o muerte) en los pacientes aleatorizados y también exclusivamente en los pacientes con tumores que tienen amplificación de FGFR2 (puntuación FISH 6). Investigar la eficacia de AZD4547 en comparación con paclitaxel mediante evaluación de la tasa de respuestas objetivas (1 respuesta a CR o PR antes de la progresión tal como se define en RECIST 1.1) en los pacientes aleatorizados y también exclusivamente en los pacientes con tumores que tienen amplificación de FGFR2 (puntuación FISH de 6). Evaluar la eficacia de AZD4547 y paclitaxel mediante la evaluación del porcentaje de pacientes sin progresión de la enfermedad a las 8 semanas. Comparar y evaluar la seguridad y la tolerabilidad de AZD4547 y paclitaxel evaluando la información de seguridad (hallazgos de laboratorio, ECG, reacciones adversas, muertes, exámenes físicos, evaluaciones oftálmicas y parámetros MUGA/Echo) Investigar la FC de AZD4547 en una población de pacientes con cáncer gástrico avanzado. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
RECIST assessments will be performed at baseline and every 8 weeks until progression. All safety measures will be collected from screening to 28 days after study drug discontinuation. Plasma AZD4547 measured as follows: Cycle 1 - Day 8 (pre), Day 15 (pre, 0.5-2, 5-6, 8-12 hrs) Cycle 2 - Day 1 (pre), Day 15 (pre, 0.5-2, 5-6, 8-12 hrs) Biomarker samples taken during screening, Cycle 1 Day 8 and Day 15, Cycle 3 Day 1 and Day 1 of each subsequent cycle. Investigate Possible pharmacokinetic/pharmacodynamic relationships between plasma AZD4547 and levels of phosphate, bFGF, FGF23, efficacy and other exploratory PD endpoints. |
Las determinaciones RECIST se realizarán al inicio y cada 8 semanas hasta la progresión Las medidas de seguridad se recogerán desde la aleatorización hasta 28 días después de la interrupción del mdto. en estudio. AZD4547 en plasma se medirá de la siguente manera: ciclo 1 - día 8 (pre), día 15 (pre, 0.5-2, 5-6, 8-12 hrs) ciclo 2 - día 1 (pre), día 15 (pre, 0.5-2, 5-6, 8-12 hrs) Las muestras de biomarcadores se tomarán durante el periodo de screening, ciclo 1 días 8 y 15, ciclo 7 día 1 y al día 1 de todos los ciclos posteriores Investigación de posibles relaciones farmacocinéticas/farmacodinámicas entre AZD4547 en plasma y niveles de fosfato, bFGF, FGF23, eficacia y otros parámetros de valoración exploratorios farmacodinámicos |
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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 | 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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
France |
Germany |
India |
Italy |
Korea, Republic of |
Spain |
Taiwan |
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
|
LVLS |
Ultima visita del último paciente |
|
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 | 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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 2 |